An Adaptive Phase 2/3 Multicenter, Double-Blind, Placebo-Controlled, Randomized, Parallel, 3 Arm Study to Evaluate the Efficacy and Safety of DA-1229 (Evogliptin) in Patient's Calcific Aortic Valve Disease With Mild to Moderate Aortic Stenosis (EVOID-AS)
A Study to Evaluate the Effectiveness and Safety of DA-1229 (Evogliptin) in Delaying Progression of Mild or Moderate Calcific Aortic Stenosis (EVOID-AS trial)
1. Male or female adult ≥ 35 years of age at time of screening.
2. Subject has calcific aortic valve disease with mild to moderate aortic stenosis as
defined by
- Doppler echocardiography results: Aortic Valve mean pressure gradient between
10-30 mmHg and Aortic Valve Area ≥ 1.2 and ≤ 2.0 cm2 on TTE within 2 weeks prior
to randomization and,
- Cardiac Compute Tomography (CT) test results: aortic valve calcium score
(Agatston score) ≥ 200 AU at baseline cardiac CT within 1 month prior to
randomization
3. Subject provides written informed consent prior to initiation of any study procedures.
4. Subject understands and agrees to comply with planned study procedures.
1. Subject has concomitant moderate or more aortic valve regurgitation.
2. Subject has concomitant moderate or severe mitral or tricuspid valve disease.
3. Subjects has left ventricular ejection fraction < 50%.
4. Subject previous history of aortic valve surgery.
5. Subject has NYHA class III or IV heart failure.
6. Subjects whose alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >
2.5 times the upper limit of normal range.
7. Subjects who cannot undergo Cardiac CT.
8. Subjects whose life expectancy is < 2 years.
9. Subjects with ESRD (End-stage Renal Disease) defined as eGFR (calculated using MDRD
equation) ≤ 30 mL/min/1.73m2 or in need of dialysis.
10. Subject has diabetes mellitus.
11. Subject has history of pancreatitis.
12. Subjects who are currently taking or anticipated to take any of the following
medications for the duration of the study:
- Insulin, DPP4 inhibitor, oral hypoglycemic agent
- Vitamin K
- Bisphosphonate
- Any medications that impact hepatic metabolism, giving rise to drug-drug
interaction (with the exception of focal treatment) CYP3A4 inducer: barbiturates,
rifampicin, carbamazepine, phenytoin
13. Subjects with history of severe allergic reaction to DPP4 inhibitors including
anaphylaxis and angioedema
14. Subjects with galactose intolerance, lapp lactase deficiency, and glucose-galactose
malabsorption
15. Subjects with history of severe cerebrovascular diseases (such as cerebral infarction
or transient ischemic attack), severe cardiovascular diseases (such as unstable
angina, myocardial infarction and life-threatening arrhythmia) within 6 months of
screening.
16. Subjects with history of malignant tumor within the past 3 years prior to Screening
Visit (Visit 1) unless cure is expected.
17. Subjects with history of drug or alcohol abuse. History of cannabis/Marijuana use
including recreational use in the last 6 months and an unwillingness to abstain during
the course of the study.
o Note: Alcohol abuse is a pattern of drinking that result in harm to one's health,
interpersonal relationships, or ability to work. Manifestations of alcohol abuse
include the following: Failure to fulfill major responsibilities at work, school, or
home, drinking in dangerous situations, such as drinking while driving or operating
machinery, legal problems related to alcohol, such as being arrested for drinking
while driving or for physically hurting someone while drunk and continued drinking
despite ongoing relationship problems that are caused or worsened by drinking
18. Subjects with history of medication non-compliance
19. Pregnant or lactating women
20. Subjects who used investigational drugs or devices within 4 weeks prior to screening
or investigational biologics within the last 6 months prior to screening.
21. Inability to provide informed consent or to comply with test requirements
22. Subjects with physical (severe hepatic, cardiac, renal, pulmonary, hematological,
endocrine, gastrointestinal, etc. conditions) or mental (cognitive, psychiatric, etc.
conditions) conditions that may impact their ability to take part in the study.
23. Consideration by the investigator, for safety reasons, that the subject is an
unsuitable candidate to receive study treatment
24. Women of child-bearing age who are sexually active but decline to take proper
contraceptive measures during the study period
- Note: To be eligible for the study, Women of childbearing potential (WOCBP) and
Women not of childbearing potential are eligible to participate. Both women of
childbearing potential and women of no childbearing potential should use an
approved method of birth control and agrees to continue to use this method for
the duration of the study (and for 30 days after taking the last dose of
investigational product).
- Acceptable methods of contraception include abstinence, female subject/partner's
use of hormonal contraceptive (oral, implanted, or injected) in conjunction with
a barrier method (WOCBP only), female subject/partner's use of an intrauterine
device (IUD), or if the female subject/partner is surgically sterile or 2 years
post-menopausal. All male subjects/partners must agree to consistently and
correctly use a condom for the duration of the study and for 30 days after taking
the study drug. In addition, subjects may not ova or donate sperm for the
duration of the study and for 30 days after taking the last dose investigational
product.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 2/8/23. Questions regarding updates should be directed to the study team contact.
Zephyrus II: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Pamrevlumab in Subjects with Idiopathic Pulmonary Fibrosis (IPF) (FibroGen095)
Zephyrus II: Effectiveness and Safety Study of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)
Key
1. Diagnosis of IPF as defined by American Thoracic Society/European Respiratory
Society/Japanese Respiratory Society/Latin American Thoracic Association
(ATS/ERS/JRS/ALAT) guidelines within the past 7 years prior to study participation.
2. High-resolution computed tomography (HRCT) scan at Screening, with ≥10% to <50%
parenchymal fibrosis (reticulation) and <25% honeycombing.
3. FVCpp value >45% and <95% at Screening and Day 1.
4. Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted ≥25% and
≤90%.
5. Previously treated with an approved IPF therapy (such as, pirfenidone or nintedanib)
but discontinued at least 1 week prior to screening, unless neither treatment is
available in the host country.
Key
1. Previous exposure to pamrevlumab.
2. Evidence of significant obstructive lung disease, as evidenced by spirometry or HRCT.
3. Female participants who are pregnant or nursing.
4. Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the
study.
5. Interstitial lung disease other than IPF.
6. Sustained improvement in the severity of IPF.
7. Other types of respiratory diseases that, in the opinion of the Investigator, would
impact the primary protocol endpoint or otherwise preclude participation in the study,
including diseases of the airways, lung parenchyma, pleural space, mediastinum,
diaphragm, or chest wall.
8. Certain medical conditions, that, in the opinion of the Investigator, would impact the
primary protocol endpoint or otherwise preclude participation in the study (such as,
myocardial infarction/stroke, severe chronic heart failure, pulmonary hypertension, or
cancers).
9. Acute IPF exacerbation during Screening or Randomization including hospitalization due
to acute IPF exacerbation within 4 weeks prior to or during screening.
10. Recent use of any investigational drugs or unapproved therapies, or participation in
any clinical trial.
11. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine
monoclonal antibodies, or to any component of the excipient.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 8/3/22. Questions regarding updates should be directed to the study team contact
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Volixibat in the Treatment of Cholestatic Pruritus in Patients with Primary Biliary Cholangitis (VANTAGE) (VANTAGE)
A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Biliary Cholangitis
- Willing and able to provide signed informed consent at the screening visit as well as comply with all study visits and requirements through the end of the study.
- Male or female, age ≥ 18 years at the screening visit.
- Have a diagnosis of PBC in line with the AASLD guidelines as demonstrated by having at least 2 of the following:
- History of sustained increased ALP levels > ULN first recognized at least 6 months prior to the screening visit (sustained ALP elevations at the time of screening is not required, recognizing that the ALP may have decreased on UDCA therapy);
- Documented positive AMA titer (> 1:40 titer on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay) or PBC-specific ANA immunofluorescence patterns (multiple nuclear dots and/or punctuate nuclear rim);
- Histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts. Liver biopsy could have been done at any time in the past.
- Those treated with UDCA will be allowed to enroll if they meet one of the following criteria at Visit 1:
- A minimum of 24 weeks of stable treatment at a dose of ≤ 20 mg/kg/day; OR
- A minimum of 12 weeks off treatment and consequently determined by the investigator to be clinically stable.
- Systemic therapies intended to address cholestatic pruritus, specifically fibrates, selective serotonin reuptake inhibitors, rifampin/rifampicin, and opioid-receptor antagonists are allowed if one of the following criteria is met at the screening visit:
- A minimum of 12 weeks of stable treatment; OR
- A minimum of 4 weeks off treatment.
- Average daily Adult ItchRO score ≥ 4 during screening to be enrolled in the study at Visit 2.
- Overall compliance of ≥ 80% in daily completion of the Adult ItchRO score in the eDiary during:
- Screening in order to be enrolled in the study at Visit 2;
- Single-blind, placebo run-in in order to be randomized at Visit 4.
- Willing to maintain an ≥ 80% average in daily completion of the Adult ItchRO between Visits 2 and 10.
- Pruritus associated with an etiology other than PBC.
- Evidence or clinical suspicion of decompensated cirrhosis or a history of decompensation events (e.g., variceal bleeding, ascites, hepatic encephalopathy, hepatorenal syndrome)
- Current symptomatic cholelithiasis or inflammatory gallbladder disease. Those with history of cholecystectomy ≥3 months before the screening visit may be eligible for enrollment.
- History of small bowel surgery/resection impacting the terminal ileum (e.g., ileostomy, ileo-anal pouch, or other surgeries/conditions) that may disrupt the enterohepatic circulation
- Evidence, history, or suspicion of other liver diseases, including but not limited to:
- Active hepatitis A or E infection;
- Active hepatitis B infection as defined by the presence of hepatitis B surface antigen (HBsAg) or presence of hepatitis B virus DNA;
- Hepatitis C as defined by the presence of hepatitis C virus (HCV) antibody and positive HCV RNA. Infection documented to have been cured for > 1 year prior to the screening visit may be eligible;
- Secondary sclerosing cholangitis, autoimmune hepatitis, PSC, immunoglobulin G4-related cholangitis, Wilson disease, alpha-1-antitrypsin deficiency, or hemochromatosis;
- Suspected or proven cholangiocarcinoma or hepatocellular carcinoma;
- History of liver transplantation;
- Histologically confirmed diagnosis of nonalcoholic steatohepatitis;
- Alcohol-related liver disease.
- Unstable and/or serious medical disease that is likely to impair the participant’s ability to participate in all aspects of the study, confound efficacy and/or safety assessments, or result in substantially shortened life expectancy (e.g., any malignancy including hematological malignancy, end-stage heart failure, active infection, acute and chronic diarrhea).
- Moderate alcohol consumption as defined for this study by > 1 and > 2 standard drinks on average per day for women and men, respectively, within 24 weeks of screening visit. A standard drink is defined as 1.5 oz (one shot) of liquor, 5 oz of nonfortified wine, or 12 oz of beer (1 oz=29.57 mL).
- Drug abuse within the 24 weeks prior to, or a positive drug screening result, at the screening visit unless it can be explained by a drug prescription:
- Use of cannabinoids (legal, prescribed, or otherwise) is allowed, provided use is stable for at least 12 weeks prior to screening and throughout the entire study duration.
- Positive for HIV antibody.
- Specific clinically significant ECG abnormalities, including but not limited to:
- Evidence of acute ischemia;
- Q-wave infarction identified within 6 months of screening visit;
- QT interval corrected using Fridericia’s correction formula (QTcF) > 470 msec (unless individual has a pacemaker);
- Congenital long QT syndrome;
- Active conduction abnormalities including:
- Mobits Type II second-degree heart block without a permanent pacemaker;
- Third-degree heart block without a permanent pacemaker;
- Untreated supraventricular tachycardia (heart rate ≥ 120 beats per minute);
- Ventricular arrhythmias (i.e., ventricular tachycardia, ventricular fibrillation, torsade de pointes);
- Uncontrolled atrial fibrillation.
- Results provided by the central laboratory for any of the following laboratory parameters collected during the screening visit:
- Platelet count ≤ 100,000/mm^3;
- Estimated glomerular filtration rate ≤ 45 mL/min, as calculated by the Chronic Kidney Disease-Epidemiology Collaboration equation;
- Serum creatinine > 2 mg/dL (178 μmol/L);
- ALT or AST > 5 × ULN.
- Note: If ALT at Visit 2 or at an unscheduled visit during the single-blind, placebo run-in is > 5 × ULN, the participant may still be enrolled if the average of the 2 ALT values from the screening visit and the eligible repeat assessment remain ≤ 5 × ULN;
- Total bilirubin > 2 × ULN, unless the individual has a diagnosis of Gilbert syndrome or hemolytic anemia as confirmed by investigator and direct bilirubin is within normal range (i.e., 0.1–0.3 mg/dL [1.7–5.1μmol/L]).
- Note: If total bilirubin at Visit 2 or at an unscheduled visit during the single-blind, placebo run-in is > 2 × ULN, he or she may still be enrolled if the average of the 2 total bilirubin values from the screening visit and the eligible repeat assessment remain ≤ 2 × ULN;
- International normalized ratio (INR) ≥ 1.7 unless due to therapeutic anticoagulation.
- Statin dosing that is not stable for a minimum of 12 weeks prior to the screening visit.
- Use of obeticholic acid treatment within 12 weeks prior to the screening visit.
- Use of an ASBT inhibitor within 24 weeks prior to the screening visit.
- Bile acid sequestrants, including cholestyramine and colestipol, within 4 weeks prior to the screening visit.
- Use of any other prohibited medication including for PBC and cholestatic pruritus as listed in the protocol within 4 weeks or 5 times the half-life, whichever is greater, prior to the screening visit.
- Women who are pregnant or nursing. Specific criteria for defining childbearing potential and acceptable methods of birth control are outlined in the protocol.
- Known intolerance/hypersensitivity to volixibat or its excipients.
- History of nonadherence to medical regimens, unreliability, medical condition, mental instability, or cognitive impairment that, in the opinion of the investigator, could compromise the validity of informed consent, compromise the safety of the participant, or lead to nonadherence with the study protocol or inability to conduct the study procedures.
- Participation in an interventional clinical study within 4 weeks OR, if applicable, 5 times the half-life, whichever is greater prior to the screening visit. Always adhere to other eligibility criteria that apply to specified concomitant medication.
Eligibility Criteria
•Open-Label Extension:
To maintain eligibility for the OLE, participants must:
- Have successfully completed the 24-week double-blind study drug treatment period.
- Have not experienced an AE(s) or SAE(s) related to volixibat during the double-blind study treatment period that led to permanent discontinuation.
- Have no changes in their medical condition or treatment that would preclude their participation in the OLE.
Eligibility last updated 5/13/22. Questions regarding updates should be directed to the study team contact.
Effects of Energy Drinks on Sleep and Cardiovascular Health in Healthy Young Adults. A Double Blind Randomized Clinical Trial
Effects of Energy Drinks on Sleep and Cardiovascular Health
- Adults 18 years of age and older.
- Healthy subjects without known cardiovascular disease and thyroid disease.
- Subjects who are on no medications (except oral contraceptive pill).
- Nonsmokers.
- No prior history of caffeine sensitivity or allergy.
- Subjects with known cardiovascular or thyroid disease.
- Subjects currently taking medications other than oral contraceptive pill.
- Smokers.
- Prior history of caffeine sensitivity or allergy.
- Pregnancy.
-
-
- Subjects who regularly consume energy drinks.
- Subjects who typically go to sleep after midnight.
- Subjects who traveled across 2 time zones in the last 7 days.
- Shift workers.
- Subjects who have or are suspected to have sleep apnea.
- Subjects who have a body mass index > 35kg/m^2.
Eligibility last updated 3/7/22. Questions regarding updates should be directed to the study team contact.
Evaluation of Voice Analysis Technology in Detecting and Managing Depression and Anxiety in Patients Undergoing Cardiac Rehabilitation
Voice Analysis Technology to Detect and Manage Depression and Anxiety in Cardiac Rehabilitation
- ≥ 18 years.
- Diagnosed myocardial infarction (MI).
- Enrolled in cardiac rehabilitation program to start within 4 weeks from hospital discharge due to MI.
- Owns a smartphone.
- Willing to download and use a smartphone app.
- Able to read, write, and speak English.
- Pregnancy.
- Actively treated for an anxiety or depressive disorder through psychotherapy or pharmacologic treatments.
- Cardiac transplant.
- Active substance use.
- Neurocognitive disorder.
- Active psychosis.
- Mania diagnosis.
Eligibility last updated 12/14/21. Questions regarding updates should be directed to the study team contact.
Cardiac MRI in Patients with Congenital Heart Disease
CMRI in CHD
- Individuals 18+ years of age.
- Capable of consent.
- Diagnosis of a Congenital Heart Disease.
- Individuals < 18 years of age.
- Unable to consent.
- Unable to undergo a cardiac MRI.
Eligibility last updated 12/21/21. Questions regarding updates should be directed to the study team contact.
A Double-Blind, Randomized, Placebo Controlled, Two Period Cross-Over Study to Evaluate the Efficacy and Safety of Orvepitant in Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis (IPF-COMFORT)
Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis
- Diagnosis of IPF established according to the 2018 joint ATS/ERS/JRS/ALAT Clinical
Practice Guideline
- FEV1/FVC ratio ≥0.65 at the screening visit
- Haemoglobin-corrected diffusion capacity of carbon monoxide (Hb-corrected DLCO) ≥25%
within 12 months of the screening visit
- Arterial oxygen saturation on room air or oxygen ≥90% at Screening
- Life expectancy of at least 12 months
- Cough that is attributed to IPF, which has not responded to anti-tussive treatment,
and which has been present for at least 8 weeks prior to Screening
- Mean daily IPF Coughing Severity Scale score ≥5.0 during the second week of the
baseline assessment period
- Recent respiratory tract infection (<8 weeks prior to Screening)
- Recent acute exacerbation of IPF (<8 weeks prior to Screening)
- Current smokers or ex-smokers with <6 months' abstinence prior to Screening
- Emphysema ≥50% on high-resolution computed tomography, or the extent of emphysema is
greater than the extent of fibrosis according to the reported results of the most
recent scan
- Mean early morning cough scale score ≥5.0 and rest of the day cough scale score <5
during the second week of the baseline assessment period (assessed at Visit 2)
- Cough that is predominantly productive in nature and attributable to lung pathology
such as chronic bronchitis or bronchiectasis
A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment for People with Severe Von Willebrand Disease (VWD) (ATHN 9)
ATHN 9: Severe Von Willebrand Disease Natural History Study
- Males and females.
- Participants with severe Von Willebrand Disease with Type 3 VWD or VWF:RCo, VWF:GPIbM or VWF:Ag ≤ 30% of pooled normal control plasma on more than one occasion.
- Participants with clinically severe VWD as defined by VWF:RCo or VWF:Ag ≤ 40% of normal with severe bleeding phenotype defined as requiring use of recurrent factor concentrates.
- Co-enrollment in the ATHN dataset.
Exclusion Criteria
- Diagnosis of platelet-type VWD;
- Diagnosis of acquired VWD (clinical diagnosis made by the hemophilia health care provider, typically based on association with hypothyroidism, lymphoproliferative and myeloproliferative disorders, malignancies and cardiovascular disease, typically aortic stenosis or LVAD).
Eligibility last updated 12/15/21. Questions regarding updates should be directed to the study team contact.
KM3D Multicenter Cancer Consortium Study: Validation of In Vitro 3D Cell Culture Models for Tumor Drug Sensitivity After Tissue Removal (KM-20-001)
In Vitro 3D Cell Culture Models Validation for Tumor Drug Sensitivity after Tissue Removal
- A demonstrated primary solid cancer for which it is medically indicated and planned to be surgically resected, biopsied, or drained (via malignant pleural effusion).
- The ability to ship the tissue sample within 24 hours of removal from the patient.
- Signed and dated consent to giving tissue as well as allowing for de-identified medical history information regarding administered treatments and treatment outcomes
to be shared.
- Over 18 years of age
- Presence of a condition(s) or diagnosis, either physical or psychological, or physical exam finding that precludes participation in the opinion of the Investigator.
TILT – T563: A Phase I Open-Label, Dose-escalation Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) in Combination with Pembrolizumab in Patients with Platinum Resistant or Refractory Ovarian Cancer (PROTA)
A Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) Combined with Pembrolizumab to Treat Refractory Ovarian Cancer
- Signed and dated informed consent(s) by the participant or legal representative before
any trial-related activities.
- Female over 18 years of age on day of signing informed consent(s).
- Histologically confirmed ovarian cancer (including fallopian tube and primary
peritoneal cancer) resistant to platinum (defined as progression of cancer within 183
days of the most recent dose of cisplatin or carboplatin) or refractory to platinum
(defined as progression of cancer within 30 days of the most recent dose of cisplatin
or carboplatin) ovarian cancer, which cannot be treated with curative intent with
available therapies. Note: Poly(ADP)-ribose polymerase (PARP) inhibitors should be
considered as indicated in clinical practice, prior to trial enrollment.
- At least one tumor (>14 mm in diameter) or carcinomatosis must be available for local
virus injection (intratumoral and/or intraperitoneal).
- The disease burden must be evaluable, but does not need to fulfil RECIST 1.1.
- Have adequate organ function as defined in the following values below. Specimens must
be collected within 10 days prior to the start of study treatment.
a. Hematological laboratory values i. Absolute neutrophil count (ANC): ≥1500/µL ii.
Platelets: ≥ 100 000/µL iii. Hemoglobin: ≥9.0 g/dL or ≥5.6 mmol/L. Criteria must be
met without packed red blood cell (pRBC) transfusion within the prior 2 weeks.
Participants can be on stable dose of erythropoietin (≥ approximately 3 months. iv.
Leukocytes (WBC) > 3.0 b. Renal laboratory values i. Glomerular Filtration Rate (GFR):
>60 ml/min (Cockcroft-Gault formula). c. Hepatic laboratory values i. Total bilirubin:
≤1.5 × Upper Limit of Normal (ULN) OR direct bilirubin ≤ULN for participants with
total bilirubin levels >1.5 × ULN (excluding patients with Gilbert's Disease) ii.
Aspartate Aminotransferase (AST) (SGOT) and Alanine Aminotransferase (ALT) (SGPT):
≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
- Patients must be willing to use adequate forms of contraception from screening, during
the trial, and for a minimum of 120 days after end of treatment, in accordance with
the following:
i. Women of childbearing potential: Barrier contraceptive method (i.e. condom) must be
used in addition to one of the following methods: Intrauterine devices or hormonal
contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings
or long-acting injections). ii. Women not of childbearing potential: Barrier
contraceptive method (i.e. condom) must be used.
- Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance
score of 0-1 at screening.
- Life expectancy longer than 3 months.
- Capable of understanding and complying with parameters as outlined in the protocol.
- Has an active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) and inhaled and topical
treatments are not considered a form of systemic treatment and are allowed.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study drug.
- Treated with any anti-cancer therapy within 30 days prior to the first virus
injection. Anti-cancer therapy is defined as anti-cancer agents (e.g. surgery,
chemotherapy, immune-checkpoint inhibitors, kinase inhibitors, PARP inhibitors,
biological therapies, hormonal therapies, radiation, etc.). Continuation of hormonal
therapy or use of bone modifying agents (e.g. bisphosphonate or denosumab) is allowed
if started at least 3 months before.
- Participants must have recovered from all Adverse Events (AE)s due to previous
therapies to ≤Grade 1or baseline. Participants with ≤Grade 2 neuropathy may be
eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or
hormone replacement may be eligible. If the participant had major surgery, the
participant must have recovered adequately from the procedure and/or any complications
from the surgery prior to starting study intervention.
- Treated with a prior radiotherapy, including for palliative purposes, within 2 weeks
of start of study treatment (before or after). Participants must have recovered from
all radiation-related toxicities, not require corticosteroids, and not have had
radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2
weeks of radiotherapy) to non-Central Nervous System (CNS) disease. Palliative
radiation is allowed from day 15 during the trial treatment period, if deemed
necessary by the investigator.
- Treated with a prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
Cytotoxic T lymphocyte-associated Antigen (CTLA)-4, Tumor necrosis factor receptor
superfamily, member 4 (OX40), CD137), and was discontinued from that treatment due to
a Grade 3 or higher immune-related Adverse Events (irAE).
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 30 days prior to the first virus
injection. An investigational agent is any drug or therapy that is currently not
approved for use in humans. Participants who have entered the follow-up phase of an
investigational study may participate as long as it has been 4 weeks after the last
dose of the previous investigational agent.
- Uncontrolled cardiac or vascular diseases.
- History of myocardial infarction or cerebral stroke within the previous 12 months
before screening or is not sufficiently recovered from an older infarction or cerebral
stroke.
- History of severe hepatic dysfunction.
- History of hepatitis B (defined as HBsAg reactive), Hepatitis C (defined as hepatitis
C virus (HCV) RNA [qualitative] is detected) and/or HIV. No testing for Hepatitis B,
Hepatitis C and HIV is required unless mandated by a local health authority.
- History of coagulation disorder.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant's
participation for the full duration of the study, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator.
- Female patients who are pregnant, breastfeeding or intend to become pregnant. Women of
childbearing potential who has a positive urine pregnancy test (within 72 hours) prior
to treatment. If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required.
- Has a known additional malignancy that is progressing or has required active treatment
within the past 5 years. Participants with basal cell carcinoma of the skin, squamous
cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical
cancer in situ) that have undergone potentially curative therapy are not excluded.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e., without evidence of progression for at least 3 months by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study treatment.
- Has an active infection requiring systemic therapy.
- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
- Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.
- Allergy to ingredients present in the investigational medicinal products (ingredients
are listed in the protocol) ie. severe hypersensitivity (≥Grade 3) to pembrolizumab
and/or any of its excipients.
- Known contraindications to pembrolizumab.
- Has had an allogenic tissue/solid organ transplant.
- Has received a live or live-attenuated vaccine within 30 days prior to the first dose
of study intervention. Administration of killed vaccines are allowed.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 3/14/23. Questions regarding updates should be directed to the study team contact.
S2104 Randomized Phase II Trial of Postoperative Adjuvant Capecitabine and Temozolomide Versus Observation in High-Risk Pancreatic Neuroendocrine Tumors
Testing the Use of Chemotherapy After Surgery for High-Risk Pancreatic Neuroendocrine Tumors
- Participants must have a histologic diagnosis of well-differentiated pancreatic neuroendocrine tumor (pNET) that was resected between 14 and 90 days prior to registration. Participants must have a scan within 90 days prior to registration without evidence of metastatic disease. Acceptable scans are multiphase computed tomography (CT) abdomen, magnetic resonance imaging (MRI) with intravenous (IV) contrast of the abdomen, or positron emission tomography (PET)-CT DOTATATE imaging if the DOTATATE PET-CT included IV iodine contrast for the CT portion of the exam.
- Resection must have been an R0 or R1 per treating investigator's assessment and/or pathology report.
- Ki-67 testing, which is considered part of standard of care in the pathology report, must have been performed between 14 and 90 days prior to registration and the result must be ≥ 3% and ≤ 55%. Treating investigators are encouraged to contact the S2104 Study Chairs and/or the study pathology chair with questions. If more than one Ki-67 is reported (e.g., primary tumor versus lymph node or metastatic site), the highest one should be considered for the study eligibility criteria.
- Participants with localized resected pNETS must have a Zaidi score of ≥ 3 derived by the following factors and points:
- 1 point; symptomatic tumor defined as one of the following:
- Gastrointestinal bleed;
- Jaundice;
- Gastrointestinal obstruction;
- Pain from primary tumor prior to surgical resection;
- Pancreatitis.
- 2 points; primary pancreas tumor size > 2 cm.
- 1 point; Ki-67 3% to 20% -1 point; lymph node positivity = 1.
- 6 points; Ki-67 21% to 55%.
- 1 point; symptomatic tumor defined as one of the following:
- Participants may have received resection/ablation of liver oligo-metastatic disease (up to 5 liver metastases) at the time of well-differentiated pNET resection.
- Participants must not have unresected or unablated metastatic disease.
- Participants must not have clinically apparent central nervous system metastases or carcinomatous meningitis.
- Participants must have recovered from effects of surgery as determined by the treating investigator.
- Participants must not have received prior neoadjuvant therapy for treatment of pancreatic neuroendocrine tumor. Use of somatostatin analogs prior to surgery is permitted.
- Participants must not have received somatostatin analogs after surgery.
- Participants must be ≥ 18 years old
- Participants must have Zubrod performance status of 0-2
- Participants must have a complete medical history and physical exam within 28 days prior to registration.
- Patients must have adequate organ and marrow function as defined below within 28 days prior to registration:
- Leukocytes ≥ 3 x 10^3/uL (within 28 days prior to registration);
- Absolute neutrophil count ≥ 1.5 x 10^3/uL (within 28 days prior to registration);
- Platelets ≥ 100 x 10^3/uL (within 28 days prior to registration);
- Total bilirubin ≤ institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 28 days prior to registration);
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN (within 28 days prior to registration);
- Serum creatinine ≤ 1.5 x institutional ULN (within 28 days prior to registration);
- Calculated creatinine clearance ≥ 50 ml/min (within 28 days prior to registration).
- Calculated Creatinine Clearance = (140
•age) X (weight in kg) † 72 x serum creatinine: - * Multiply this number by 0.85 if the participant is female.
- † The kilogram weight is the participant weight with an upper limit of 140% of the IBW.
- * Actual lab serum creatinine value with a minimum of 0.8 mg/dL.
- Participants must be able to swallow pills.
- Participants must be able to tolerate CT or magnetic resonance (MR) imaging including contrast agents as required for their treatment and the protocol.
- Participants must not be planning to receive warfarin while on protocol treatment. Other anticoagulants are allowed.
- Participants must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine.
- Participants must not have known absorption issues that would limit the ability to absorb study agents.
- Participants must not have had an arterial thromboembolic event, unstable angina, or myocardial infarction within 12 months prior to registration.
- Participants must not have active or uncontrolled infection.
- Participants must not have serious medical or psychiatric illness that could affect study participation in the judgement of the treating investigator.
- Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential."In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen.
- No other active malignancy or history of prior malignancy is allowed, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years.
- Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.
- Participants must not have unresected or unablated metastatic disease.
- Participants must not have clinically apparent central nervous system metastases or carcinomatous meningitis.
- Participants must not have received prior neoadjuvant therapy for treatment of pancreatic neuroendocrine tumor. Use of somatostatin analogs prior to surgery is permitted.
- Participants must not have received somatostatin analogs after surgery.
- Participants must not be planning to receive warfarin while on protocol treatment. Other anticoagulants are allowed.
- Participants must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine.
- Participants must not have known absorption issues that would limit the ability to absorb study agents.
- Participants must not have had an arterial thromboembolic event, unstable angina, or myocardial infarction within 12 months prior to registration.
- Participants must not have active or uncontrolled infection.
- Participants must not have serious medical or psychiatric illness that could affect study participation in the judgement of the treating investigator.
- Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen.
Eligibility last updated 12/27/21. Questions regarding updates should be directed to the study team contact.
Evaluating Paternal Antigen Exposure and Maternal Immune Tolerance
Evaluating Paternal Antigen Exposure
- Pregnant patients seen for prenatal care in Rochester and deliver within the Mayo Clinic Health Systems
- Ability to provide informed written consent
- Known paternity for pregnancy
- Singleton pregnancies
- Mothers < 18 years of age
- Multiple fetuses
Eligibility last updated 9/8/22. Questions regarding updates should be directed to the study team contact.
Mayo Clinic Phage Program Biobank (Phagebank)
Mayo Clinic Phage Program Biobank
- ≥ 18 years of age.
- Able to provide informed consent.
- Individual must have a future treatment plan to receive or has historically received phage therapy.
- Individuals , 18 years of age.
- Unwilling/unable to provide informed consent.
Eligibility last updated 1/10/22. Questions regarding updates should be directed to the study team contact.
A Randomized, Double-blind, Placebo-controlled Phase 2 Study with Open Label Extension to Assess the Efficacy and Safety of Namilumab in Subjects with Chronic Pulmonary Sarcoidosis
Namilumab in Subjects with Chronic Pulmonary Sarcoidosis
- Male or female age ≥ 18 years.
- Is able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form.
- Have a ≥ 6-month history of documented sarcoidosis including histological confirmation in the subject’s medical records.
- Have high-resolution computed tomography (HRCT) and PET scan consistent with active pulmonary sarcoidosis of the lung parenchyma confirmed by central read.
- Have FVCp ≥ 50% to ≤ 90% and DLCO ≥ 50%.
- If receiving prednisone (or equivalent), dose must have been ≤25 mg, and dose must have been stable for at least 4 weeks prior to randomization.
- Symptomatic as indicated by mMRC Dyspnea scale >1 (i.e., Grade 2 or more) in the prior year.
- If receiving methotrexate and/or other immunosuppressive therapy (IST) dose must have been stable for ≥ 3 months prior to randomization.
- Female subjects must agree to use an approved highly effective birth control (BC) method (< 1% failure rate per year) throughout the study, unless documented to have a reproductive status of non-childbearing potential or is postmenopausal:
- Non-childbearing potential defined as pre-menopausal female with medical history of bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries), or hysterectomy; hysteroscopic sterilization;
- Postmenopausal defined as 12 months of spontaneous amenorrhea; otherwise, a follicle stimulating hormone (FSH) confirmation will be required. For females with questionable menopausal history (e.g., irregular menstrual periods and age > 40 years) a documented serum FSH level must be ≥ 30 mIU/mL;
- Woman of childbearing potential (WCBP) who is already using an established method of highly effective contraception or agrees to use one of the allowed BC methods, for at least 28 days prior to the start of dosing, throughout the study, and for 4 months following the last dose of study drug.
- Males who are sexually active must agree to use one of the allowed BC methods. Male subjects must also agree to sufficiently minimize the risk of pregnancy throughout study participation (and for 4 months following the last dose of study drug).
- Body Mass Index (BMI) 18 to 40 kg/m^2 at screening.
- Subjects must agree to steroid taper, and cessation of their IST therapy at randomization.
- Completion of vaccination for COVID-19 at least 2 weeks prior to randomization.
Exlusion Criteria:
- Hospitalized for any respiratory illness ≤ 30 days prior to screening.
- Prednisone dose > 25 mg/day at any time in the previous 4 weeks.
- ≥ 20% fibrosis as indicated on CT-scan that has been confirmed by central read prior to randomization.
- eGFR ≤30 mL/min/1.73 m^2 (MDRD equation) or requiring hemofiltration or dialysis.
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 3 × upper limit of normal range (ULN).
- Platelet count <100,000 per mm^3.
- Hemoglobin ≤ 9.5 g/dL.
- Absolute neutrophil count < 1,000 per mm^3.
- History of known anti-GM-CSF autoAb or tests positive at screening, or history of pulmonary alveolar proteinosis (PAP).
- Use of biologic — approved or investigational agents (e.g., anti-TNFα, anti-IL-1, anti-IL-6, anti-IL-17, anti-IL-12/23 or specific anti-IL-23 inhibitors, anti CD20, anti-IL-18) within the 6 months prior to screening.
- Prior use of immunoglobulin within 6 months prior to screening.
- Prior use of any investigational immunomodulator (e.g., NRP2 modulator) within 6 months of screening.
- Prior use of any JAK inhibitor within 3 months of screening.
- Participation in another interventional clinical trial within 6 months prior to screening.
- Known left ventricular ejection fraction (LVEF) ≤30% or NYHA class III or IV heart failure.
- ECG abnormalities that warrant further investigation, in the opinion of the Investigator.
- Pulmonary hypertension requiring therapy.
- Systolic blood pressure (SBP) < 90 or > 180 mm Hg; Diastolic blood pressure (DBP) < 60 or > 110 mm Hg.
- Known COVID-19 infection within 3 months prior to screening.
- Have received any live virus or bacterial vaccinations < 3 months of screening. Age-appropriate non-live vaccinations may be administered during screening so long as the last vaccine dose is administered at least 2 weeks prior to planned randomization.
- Any infection requiring antibiotics or pulse of OCS where completion of treatment has been < 30 days prior to screening.
- History of 3 or more lower respiratory tract infections requiring anti-microbial therapy in the past year.
- Any history of mycetoma or fungal respiratory infection.
- Requirement for supplemental oxygen at rest.
- Prior history of, or likely to have any organ transplantation during study including OLE.
- History of smoking (or vaping) in the prior year or current use. Occasional use (defined as less frequently than once per month) is allowable, though subjects should be counseled to remain abstinent during the study including OLE.
- Other significant pulmonary disease likely to interfere with the primary endpoint, in the opinion of the Investigator.
- Other autoimmune disease likely to require therapy during the study.
- Symptoms and features of extra-PS that may warrant treatment in addition to that required for lung involvement.
- Significant ischemic heart disease (i.e., myocardial infarction within 6 months, unstable angina or PCTA/stent within 1 month or planned intervention during study).
- Known or suspected active and untreated/inadequately treated tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis B or C infection. Subjects with latent TB may be enrolled if anti-TB therapy is commenced prior to randomization.
- For women: pregnant or planning to become pregnant during the study or currently breastfeeding.
- Prior history of any malignancy or lymphoproliferative disorder (not including fully resected basal cell carcinoma of the skin, fully resected intra-epithelial neoplasia or carcinoma in situ) within the past 5 years.
Eligibility last updated 12/23/21. Questions regarding updates should be directed to the study team contact.
Remote Monitoring with Health-Coaching for Lifestyle Changes in Patients with Lung Cancer Related Fatigue
Remote Monitoring for Lifestyle Changes in Patients with Lung Cancer Related Fatigue
- Age ≥ 18 years.
- Diagnosed with advanced NSCLC being treated with any line of non-curative intent, systemic treatment.
- Eastern Cooperative Oncology Group (ECOG) Performance Status from 0 (asymptomatic) to 2.
- The ability to read and respond to questions in English or Spanish.
- Receiving primary cancer care at Mayo Clinic, Rochester or MCHS.
- Life expectancy at least 6 months.
- Individuals < 18 years.
- Patients wioth cognitive or psychiatric conditions as determined by the treating oncologist to prohibit study consent or participation.
Eligibility last updated 12/21/21. Questions regarding updates should be directed to the study team contact.
A Retrospective, Multicenter Study of Open Nipple Sparing Mastectomy (NSM)
Open Nipple Sparing Mastectomy (NSM)
- All female patients that have undergone open prophylactic NSM cases performed between January 1, 2018 through 42 days prior to IRB approval.
- Patients who have not undergone open prophylactic NSM surgery.
Eligibility last updated 12/29/21. Questions regarding updates should be directed to the study team contact.
Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease (ABCVILD)
Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease
- Diagnosis of CVID according to the international consensus document (ICON):
- Age 4 years or above;
- Serum IgG at least 2 standard deviations below the age adjusted normal;
- Decreased serum IgA and/or serum IgM;
- Abnormal specific antibody response to immunization;
- Exclusion of secondary immunodeficiency.
- On replacement immunoglobulin for at least 6 months and willing to maintain throughout study.
- Granulomatous-lymphocytic interstitial lung disease with a lymphocytic component diagnosed by lung biopsy prior to study entry, wedge biopsy preferred.
- Persistence or worsening of interstitial lung disease measured on serial CT imaging of the lung at least 6 months apart, with the latest assessment within 2 months of study entry.
- Signed written informed consent.
- Willing to allow storage of biological specimens for future use in medical research.
- Females of childbearing potential must use a highly effective form of birth control such as hormone-based contraceptive, intrauterine device, or double barrier method.
- History of hypersensitivity to abatacept or any of its components.
- Has received any lymphocyte depleting agents including anti-CD20 monoclonal antibodies, alemtuzumab, ATG in the preceding 6 months.
- Has received abatacept, cyclophosphamide, tumor necrosis factor inhibitors, or pulse steroids (defined as >15mg/kg/day of methylprednisone or corticosteroid equivalent) within the past 3 months.
- History of HIV infection (positive PCR).
- Chronic untreated hepatitis B or C (positive PCR).
- Active tuberculosis (TB) by positive QuantiFERON gold. If history of latent TB, then must supply evidence of completing treatment.
- Persistent Epstein-Barr Virus (EBV) load ≥ 1,000 units/mL blood checked twice at least 1 month apart.
- Other uncontrolled infections.
- Live vaccine given within 6 weeks of the start of the trial.
- Malignancy or treated for malignancy within the past year.
- Currently pregnant or breast feeding.
- Life expectancy less than 1 month.
- Subjects unwilling to self-administer or have a parent/caregiver self-administer subcutaneous injections at home.
- Other conditions that the investigators feel contraindicate participation in the study.
Eligibility last updated 12/22/21. Questions regarding updates should be directed to the study team contact.
Cardiovascular and Cognitive Implications of CNS hypersomnias and Their Treatments (CVCOGNARCIH)
Does Narcolepsy/Idiopathic Hypersomnia and Their Treatment(s) Alter Blood Pressure and Cognition
- Diagnosed with a CNS hypersomnia according to ICSD-3 classifications.
- Age 18
•75 years. - BMI between 18 and 40 kg/m^2.
- Prescribed a medication of interest (e.g., sodium oxybate, low sodium oxybate, pitolisant, modafinil/armodafinil, solriamfetol) by a clinical sleep specialist as part of routine medical care and covered by subject’s health insurance plan.
- If subject has not yet started the prescribed medication, then subject must be willing to postpone starting medication until after completion of baseline assessment(s).
- If subject has been taking a prescribed medication at a stable dose for at least 3 months and has been prescribed a new medication, then then subject may complete baseline assessment(s) while taking initial medication before starting new medication.
- Any change to medication(s) within the last 45 days.
- History of chronic alcohol or drug abuse within the prior 12 months.
- Heart failure, history of severe hypertension, or other cardiovascular disease compromising the patient's wellbeing or ability to participate in this study.
- Use of any sleep apnea treatment (e.g., Positive Airway Pressure (PAP) therapy, oral appliance therapy, etc.) within 45 days of baseline assessment visit.
- Participation in another study of an investigational drug within the 28 days prior to screening visit or currently.
- Pregnancy and/or breast-feeding.
- Subjects who, in the opinion of the Investigator, may not be suitable for the study.
Eligibility last updated 4/28/22. Questions regarding updates should be directed to the study team contact.
Screening for High Frequency Malignant Disease (SHIELD) (SHIELD)
Screening for High Frequency Malignant Disease
- Subject aged 50-80 years at time of consent.
- Increased risk of lung cancer defined by having at least 20 pack-year smoking history and currently smoke or have quit within the past 15 years.
- Undergoing or intended to undergo low dose CT scan of the chest for lung cancer screening.
- Willing to consent to the investigational blood draw during index low dose CT scan screening visit and before any invasive procedures or treatment for lung cancer diagnosis.
- Willing to consent to a 1-year, 2-year and additional follow-up per protocol.
- Subject has not smoked for 15 or more years.
- Subject has less than 20 pack-year smoking history.
- Subject has a health problem that substantially limits life expectancy and/or the ability or willingness to have curative lung surgery.
- Subject undergoing low-dose CT scan of the chest for investigation of symptoms suspicious for lung cancer.
- Preexisting or history of lung cancer.
- Previously diagnosed high-risk lung lesion.
- History of any malignancy (subjects who have undergone surgical removal of skin squamous cell cancer may be enrolled provided the procedure was completed at least 12 months prior to the date of provision of informed consent for the study).
- Currently taking any anti-neoplastic or disease-modifying anti-rheumatic drugs.
- Currently receiving treatment for pneumonia.
- Any major physical trauma (e.g., disruption of tissue, surgery, organ transplant, blood product transfusion) within the 30 days leading up to the provision of informed consent.
- Known medical condition which, in the opinion of the investigator, should preclude enrollment into the study.
- Participation in a clinical research study in which an experimental medication and/or medical procedure has been administered or may be administered within the 30 days leading up to providing informed consent or may be administered through the time of subject screening.
- Additional cohorts: inclusion and exclusion criteria will be specified for each cohort as appendixes.
Eligibility last updated 1/21/22. Questions regarding updates should be directed to the study team contact.
Tonation Breathing Technique, a Non-pharmacogenic Method to Ease Aromatase Inhibitor-induced Musculoskeletal Symptoms - A Pilot Study (TBT)
Ease Aromatase Inhibitor-induced Musculoskeletal Symptoms
- Eligible patients are females with stage I-III breast cancer taking adjuvant AI (either standard dose of anastrozole 1 mg daily or letrozole 2.5 mg daily or exemestane 25 mg daily) for greater than 30 days experiencing AI induced musculoskeletal pain scores of 5 or higher on a Likert scale will be enrolled. Treating physicians determine if pain is secondary to an AI.
- ≥ 18 years old.
- Subjects should have completed any planned surgery for breast cancer, chemotherapy and radiation therapy at least 30 days prior to enrollment.
- Patients should have an ECOG performance score of 0-2.
- Age less than 18 years.
- Significant underlying pulmonary disease.
Eligibility last updated 1/14/22. Questions regarding updates should be directed to the study team contact.
Prospective Collection of Blood and Urine of Healthy Individuals for Liquid Biopsy Research (HDEV)
Liquid Biopsy Controls
- Able to give informed consent.
- Adults > 50 years old.
- No prior cancer diagnosis.
- Individuals < 50 years old.
- Unable or unwilling to provide informed consent.
Eligibility last updated 12/30/21. Questions regarding updates should be directed to the study team contact.
Myocardial 123I-MIBG Scintigraphy in Aging and Neurodegenerative Disease (MIBG)
Utility of MIBG Scintigraphy in Aging and Neurodegenerative Disease
- Diagnosis of one of one of the syndromes/diagnoses of interest using established criteria.
- Age ≥ 40 to ≤ 90 inclusive.
- STMS score above 10.
- No active medical disorder that could preclude participation.
- Stable medication regimen over previous four weeks.
- Absence of certain medications that could significantly impact the myocardial 123I-MIBG.
- For those with dementia, caregiver that is with the patient at least four hours/day for at least five days per week.
- For those with dementia , or severe parkinsonism, patient and caregiver willing and able to participate in all study-related procedures.
- Patient is capable of giving informed consent, or if apropriate, has caregiver capable of giving consent on the subject's behalf.
- Does not fulfill criteria for any of the desired diagnoses.
- Age > 40 or < 90.
- Women with intact uterus and not post-menopausal unless pregnancy test performed at screening is negative.
- Women who are pregnant or are breast-feeding an infant.
- STMS score < 10.
- Active medical disorder that could preclude participation in this protocol:
- Hypersensitivity to the radioligand or iodine;
- Myocardial infarction or cerebral infarct over preceding year, stable or unstable angina, known symptomatic coronary artery disease;
- Renal disease viewed by the physician to be too severe to warrant myocardial 123I-MIBG scintigraphy imaging;
- History of significant alcohol or drug abuse;
- Any other medical disorder considered by the study physicians as inappropriate for enrollment in this protocol.
- Patient or caregiver unwilling or unable to participate in all study-related procedures.
- Caregiver is not with a patient with dementia or severe parkinsonism at least 4 hours/day for at least 5 days/week.
- Patient or caregiver unwilling or unable to provide informed consent.
Eligibility last updated 1/4/22. Questions regarding updates should be directed to the study team contact.
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Subjects With Immunoglobulin A Nephropathy. (Otsuka)
Visionary Study: Phase 3 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy (IgAN)
- Male and female patients ≥ 18 years of age .
- Biopsy-confirmed IgAN. (Patients with an eGFR of 30 to 45 mL/min/1.73m^2 must have had
a kidney biopsy performed within 36 months of the screening visit).
- Stable and maximally tolerated dose of ACEI and/or ARB for at least 3 months prior to
screening. Patients who are on a stable dose of SGLT2i may participate if treatment
was initiated ≥3 months prior to screening. Patients who are unable to take an ACEI or
ARB may participate if their overall management conforms with standards of care and
other protocol requirements.
- Screening urine protein/creatinine ratio (uPCR) ≥ 0.75 g/g or urine protein ≥ 1.0
g/day.
- eGFR ≥ 30 mL/min/1.73 m2, (for the exploratory cohort only: eGFR 20- <30 mL/min/1.73
m2), calculated using the CKD-EPI equation).
- Secondary forms of IgAN or IgA vasculitis.
- Coexisting chronic kidney disease other than IgAN.
- Kidney biopsy findings in addition to IgAN including those of diabetic nephropathy,
membranous nephropathy, or lupus nephritis. Hypertensive vascular changes are
acceptable.
- Kidney biopsy MEST or MEST-C score of T2 or C2 (Oxford IgAN classification). If
MEST-scoring was not performed, the presence of > 50% tubulo-interstitial fibrosis, or
crescents in > 25% of glomeruli is exclusionary. This does not apply to the
exploratory cohort.
- Nephrotic syndrome.
- Serum IgG < 600 mg/dL at screening.
- Chronic systemic immunosuppression, including glucocorticoids, within 16 weeks of
randomization.
- Participation in another interventional clinical trial and receipt of another
investigational drug within 30 days prior to the administration of IMP or 5 half-lives
from last investigational drug administration, whichever is longer.
- Chronic infectious disease, or acute infectious disease at time of screening.
- Type 1 diabetes, or poorly controlled Type 2 diabetes.
- Uncontrolled hypertension.
The protocol provides additional information about these and other inclusion and exclusion
criteria.
A Protocol to Establish a Biobank of Controls for Post-COVID Studies
COVID Controls
- Age ≥ 18 years.
- Age and gender matched to biorepository cohort.
- Population specific:
- For the never-COVID group – no history of having contracted COVID;
- For COVID infection without post COVID cohort (+ COVID,
•PASC), part of initial acute COVID biorepository; - time from onset of symptoms matched to biorepository cohort.
- For the + PASC group Included in the PASC biorepository.
- Matched by age, sex and time of onset of symptoms, as appropriate be able to participate fully in all aspects of the study; and
- Have understood and signed study informed consent.
- Active persistent COVID infection.
- < 40 kg in weight have a known history of any condition or factor judged by the investigator to preclude participation in the study or which might hinder adherence.
- Women with a previously confirmed infection with the novel SARS-CoV-2 virus of childbearing potential and pregnant women will be offered enrollment because there is no risk to an unborn child in this investigation.
Eligibility last updated 3/2/22. Questions regarding updates should be directed to the study team contact.
A Phase 1a/1b, Open-Label, Multi-Center, Dose Escalation and Expansion Study of HFB200301 (TNFR2 Agonist Antibody) as a Single Agent and in Combination With Tislelizumab (Anti-PD-1 Antibody) in Adult Patients With Advanced Solid Tumors
A Study of HFB200301 in Adult Patients With Advanced Solid Tumors
- Previously received the following lines of systemic therapy for the
advanced/metastatic disease:
- Gastric cancer: at least 2 lines of therapy
- Renal cell carcinoma: at least 2 lines of therapy
- Melanoma:
- BRAF V600E mutant: must have received at least 2 lines of therapy
- BRAF V600E wild type: must have received at least 1 line of therapy
- Sarcoma: at least 1 line of therapy
- Testicular germ cell tumor: at least 2 lines of therapy
- Cervical cancer: at least 2 lines of therapy
- Mesothelioma: at least 2 lines of therapy
- Non-small cell lung cancer: at least 3 lines of therapy
- Head and neck squamous cell carcinoma: at least 2 lines of therapy
- Suitable site to biopsy at pre-treatment and on-treatment
- Measurable disease as determined by Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 or modified RECIST (mRECIST) for mesothelioma
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Systemic anti-cancer therapy within 2 weeks prior to start of study drug
- For soft tissue sarcoma and testicular germ cell tumor patients only: prior immune
therapy
- Therapeutic radiation therapy within the past 2 weeks
- Prior exposure to agents targeting the Tumor Necrosis Factor Receptor type 2 (TNFR2)
receptor
- Active autoimmune disease requiring systemic treatment in the previous 2 years
- Systemic steroid therapy (>10 mg/day of prednisone or equivalent) or any immune
suppressive therapy
- Persisting toxicity of ≥Grade 2 (≥Grade 1 for diarrhea) relating to prior anti cancer
therapy with the following exceptions:
- All grades of alopecia are acceptable
- Endocrine dysfunction on replacement therapy is acceptable
- Severe or unstable medical condition, including uncontrolled diabetes, coagulopathy,
or unstable psychiatric condition
- Major surgery within 2 weeks of the first dose of study drug
- History or presence of drug or non-drug induced interstitial lung disease or
pneumonitis ≥Grade 2
- History of allergic reactions, immune related reactions, or cytokine release syndrome
(CRS) attributed to compounds of similar chemical or biologic composition to
monoclonal antibodies or any excipient of HFB200301
- Using sensitive substrates of major cytochrome P450 (CYP450) enzymes
- Known active malignancy, with the exception of the specific cancer under investigation
in this trial, that required treatment within the previous 2 years
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 11/15/22. Questions regarding updates should be directed to the study team contact.
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose, Multicenter Study to Examine the Efficacy and Safety of ZX008 in Subjects with CDKL5 Deficiency Disorder Followed by an Open-Label Extension (Zogenix ZX008-2103)
A Study to Investigate the Effectiveness and Safety of ZX008 in Subjects with CDKL5 Deficiency Disorder
- Subject has a confirmed pathogenic or likely pathogenic mutation in the CDKL5 gene and
a clinical diagnosis of CDD with epilepsy onset in the first year of life, plus motor
and developmental delays.
- Subject is male or female, aged 1 to 35 years, inclusive, as of the day of the
Screening Visit.
- Subject must have failed to achieve seizure control despite previous or current use of
2 or more AETs.
- Subject is currently receiving at least 1 concomitant antiseizure treatment:
antiseizure medication (ASM), vagus nerve stimulation (VNS), responsive
neurostimulation (RNS), or ketogenic diet (KD).
- All medications or interventions for epilepsy (including VNS, RNS, and KD) must be
stable prior to screening and are expected to remain stable throughout the study.
- At the Screening Visit, parent/caregiver reports that subject has ≥ 4 countable motor
seizures(CMS) per week.
- Subject has a known hypersensitivity to fenfluramine or any of the excipients in the
study drug.
- Subject has a diagnosis of pulmonary arterial hypertension.
- Subject has a clinically significant medical condition, including chronic obstructive
pulmonary disease, interstitial lung disease, or portal hypertension, or has had
clinically relevant symptoms or a clinically significant illness currently or in the 4
weeks prior to the Screening Visit, other than epilepsy, that would negatively impact
study participation, collection of study data, or pose a risk to the subject.
- Subject has current or past history of cardiovascular or cerebrovascular disease, such
as cardiac valvulopathy, myocardial infarction or stroke, severe ventricular
arrhythmias, or clinically significant structural cardiac abnormality, including but
not limited to mitral valve prolapse, atrial or ventricular septal defects, patent
ductus arteriosus, and patent foramen ovale with reversal of shunt. (Note: Patent
foramen ovale or a bicuspid aortic valve are not considered exclusionary).
- Subject has moderate to severe hepatic impairment.
- Subject has current eating disorder that suggests anorexia nervosa or bulimia.
- Subject has a current or past history of glaucoma.
- Subject is taking > 4 concomitant ASMs. Rescue medications are not included in the
count.
- Subject is receiving concomitant treatment with cannabidiol (CBD) other than
Epidiolex/Epidyolex or is being actively treated with tetrahydrocannabinol (THC) or
any marijuana product for any condition.
- Subject has participated in another interventional clinical trial within 30 days of
the Screening Visit or is currently receiving an investigational product.
- Subject has previously been treated with Fintepla® (fenfluramine) prior to the
Screening Visit.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 2/1/23. Questions regarding updates should be directed to the study team contact.
A Single-Arm, Open-Label, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of Taletrectinib in Patients With Advanced or Metastatic ROS1 Positive NSCLC and Other Solid Tumors (TRUST-II)
Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC
1. Age ≥18 years (or ≥20 years as required by local regulations).
2. Histologically or cytologically confirmed diagnosis of locally advanced (including
inoperable Stage IIIA or IIIB NSCLC) or metastatic NSCLC or other solid tumors.
3. Evidence of ROS1 fusion by a validated assay.
4. Patients with central nervous system (CNS) involvement, including leptomeningeal
carcinomatosis, must be stable, either asymptomatic or previously treated and
controlled within 14 days of first dose.
5. The patient can be either ROS1 TKI treatment naïve or treated with prior ROS1 TKI(s).
6. The patient must have at least 1 measurable disease per RECIST 1.1 as assessed by the
investigator.
7. Eastern Cooperative Oncology Group Performance Status: 0 or 1.
8. Patient with a life expectancy ≥12 weeks based on the judgement of investigator.
9. Patients with adequate organ function meeting the following criteria:
1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤3.0 × upper
limit of normal (ULN) (or ≤5.0 × ULN, for patients with concurrent liver
metastases)
2. Serum total bilirubin: ≤1.5 × ULN (≤3.0 × ULN for patients with Gilbert syndrome
or if liver function abnormalities are due to underlying malignancy)
3. Absolute neutrophil count: ≥1,500/?L
4. Platelet count: ≥100,000/?L
5. Hemoglobin: ≥9.0 g/dL
6. Serum creatinine ≤1.5 × ULN
10. Patients must be able to practice required contraception during the study.
1. For males (irrespective of surgical sterilization [vasectomy]): agree to use
effective contraception methods during the study intervention period and for at
least 90 days after the last dose of investigational drug or agree with complete
abstinence.
2. Females without menses for at least 1 year prior to screening or documented to be
surgically sterilized. Women of childbearing potential (WOCBP) must agree to use
two concurrent highly effective methods of contraception or agree with complete
abstinence from sexual intercourse since the informed consent until 45 days after
the last dose of investigational drug. The patient is willing and capable to give
written informed consent.
11. The patient is willing and capable to comply with the study scheduled visits,
treatment plans, laboratory tests and other procedures.
12. The patient is willing and capable to comply with study site's COVID-19 policies.
Exclusion Criteria
1. Treatment with small molecule anticancer therapy including other investigational
agents or cytotoxic systemic anticancer therapy within 2 weeks (or 5 half-lives of the
compound, whichever is shorter) prior to the first dose of taletrectinib; Treatment
with immuno-oncology (IO) including immune checkpoint inhibitors within 4 weeks before
the first dose of taletrectinib.
2. Major surgical procedure, open biopsy, or significant traumatic injury ≤4 weeks before
the first dose of taletrectinib.
? Placement of vascular access device is not considered major surgery. Other minor
surgical procedures, such as catheter placement or minimally invasive biopsy, are
allowed.
3. Radiotherapy within 14 days before study treatment. Stereotactic radiosurgery (SRS),
stereotactic radiation therapy (SRT), and palliative radiation outside the chest and
brain are allowed but must be completed 1 week before starting study treatment.
4. Have been diagnosed with another primary malignancy other than NSCLC except for
adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively
treated non-metastatic prostate cancer; or patients with another primary malignancy
who are definitively relapse-free with at least 3 years elapsed since the diagnosis of
the other primary malignancy. Note: This criterion does not apply to patients to be
enrolled in Cohort 4.
5. Adverse events due to prior therapy are unresolved to ≤ CTCAE Grade 1 or has not
returned to baseline, by the first dose of taletrectinib except for AEs not
constituting a safety risk to the patient based on the judgment of investigators.
6. Patients with untreated spinal cord compression caused by tumor and/or cancerous
meningitis.
7. History or evidence of interstitial fibrosis, interstitial lung disease or
drug-induced pneumonitis.
8. Any gastrointestinal disorders that may affect absorption of oral medications.
9. Active and clinically significant bacterial, fungal, or viral infection including
hepatitis B virus (HBV), hepatitis C virus (HCV), or severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), known human immunodeficiency virus (HIV) or acquired
immunodeficiency syndrome (AIDS)-related illness.
10. Clinically significant cardiovascular diseases within 3 months prior to the first dose
of taletrectinib: myocardial infarction, severe/unstable angina, coronary/peripheral
endovascular treatment, heart failure or cerebrovascular disorder including transient
ischemic attack.
11. Ongoing cardiac dysrhythmias of ≥ CTCAE Grade 2, uncontrolled atrial fibrillation of
any grade, or QT interval corrected for heart rate by Fredericia's formula (QTcF) >470
milliseconds, or symptomatic bradycardia <45 beats per minute; patient has family or
medical history of long QT syndrome.
12. Pregnancy or lactation/breastfeeding.
13. Use of food or drugs that are known potent cytochrome P450 3A4/5 (CYP3A4/5) inhibitors
or inducers or P-glycoprotein inhibitors or inducers within 14 days prior to the first
dose of study treatment and while on treatment.
14. Administration of agents with potential QT interval prolonging effect within 14 days
prior to first dose of study treatment and while on treatment.
15. Patients with other severe medical or mental diseases in whom the risk is increased by
the participation to the study or treatment with study treatment in the opinion of the
investigator.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 5/9/23. Questions regarding updates should be directed to the study team contact.
The Effects of Glucagon on Hepatic Metabolism
The Effects of Glucagon on Hepatic Metabolism
- Willing to participate
- Able to give consent
- History of prior upper abdominal surgery e.g. gastric banding, pyloroplasty, vagotomy.
- Active systemic illness or malignancy.
- Symptomatic macrovascular or microvascular disease.
- Contraindications to MRI (e.g. metal implants, claustrophobia).
- Hematocrit < 35%
- TSH < 0.4 or > 5.5.
- Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT
questionnaire
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 4/6/23. Questions regarding updates should be directed to the study team contact.
Alaska Native Family-Based, Financial Incentives Intervention for Smoking Cessation
Alaska Native Family-Based, Financial Incentives Intervention for Smoking Cessation
Index Participants will be eligible if they:
- Are an ANAI person (based on self-reported race/ethnicity) and reside in Alaska.
- Are aged ≥ 21 years (legal smoking age in Alaska).
- Self-report smoking in the past 7 days, biochemically verified with breath expired air carbon monoxide (CO) > 4 ppm and saliva cotinine > 30 n/ml (positive Alere iScreen result).
- Smoked > 3 cigarettes per day (cpd) over the past 3 months.
- If other tobacco or nicotine product used, cigarettes are the main tobacco product used.
- Are considering or willing to make a quit attempt.
- Own or have access to a mobile phone or tablet with Internet and text messaging capabilities, or will be loaned an iPad mini for the study duration.
- Nominate one adult family member who will enroll.
- Used pharmacotherapy or a stop smoking program within the past 3 months.
- Another person in the household is enrolled as the index participant.
Family Member Participants, regardless of smoking status or residence with the index participant, will be eligible if they:
- Are ≥ 21 years old.
- Are defined as family by the index participant.
- Own or have access to a mobile phone or tablet with internet and text messaging capabilities or will be loaned an iPad mini for the study duration.
- Both men and women and those from non-ANAI racial/ethnic groups.
- Family members may only support one index participant to mitigate concern about lack of independence of household or other support networks, and potential for crosstreatment contamination, which could attenuate effects in the RCT.
Alaska Tribal Health System stakeholders:
- Input from healthcare providers, cessation specialists, and THO leaders will be gathered to understand potential facilitators and barriers to adoption of the intervention within the ATHS. The ANTHC team will invite individuals to participate through phone and email communications.
Eligibility last updated 1/17/22. Questions regarding updates should be directed to the study team contact.
Evaluation of Cochlear Implantation at Mayo Clinic (ECI)
Evaluation of Cochlear Implantation
- All patients that underwent cochlear implantation at the Mayo Clinic starting 1/1/1982.
- If patients declined MN research authorization, they may be contacted for consent for approval.
- Patients that did not undergo cochlear implantation at the Mayo Clinic.
Eligibility last updated 1/7/22. Questions regarding updates should be directed to the study team contact.