Study of M5049 in DM and PM Participants (NEPTUNIA)
• Diagnosis of probable or definite DM or PM as per 2017 ACR/EULAR classification criteria, with positive autoantibody status. Anti-synthetase syndrome (ASyS) participants that meet classification criteria are allowed
• Active disease on standard of care (SoC), must meet 1 of the criteria within 6 months prior to Screening: Pathological evidence of active myositis in muscle biopsy; Evidence of active myositis by Electromyography (EMG); Magnetic resonance imaging (MRI) with evidence of active myositis; or any muscle enzyme greater than or equal to (>=) 4 × upper limit of normal (ULN) at time of Screening; Active PM/DM skin rash as per cutaneous dermatomyositis area and severity index-A (CDASI-A) >= 7 at time of Screening
• Minimum disease severity defined by: moderate to severe myopathy with manual muscle testing-8 (MMT-8) >= 80 and less than or equal to (<=) 142 AND at least 2 of the following core set measures (CSM) abnormalities: Patient Global Activity (PtGA) >= 2 centimeters (cm); Physician Global Activity (PGA) derived from myositis disease activity assessment tool (MDAAT) >= 2 cm; Extramuscular Activity Assessment derived from MDAAT >2 cm; At least 1 muscle enzyme > 1.5 times ULN; health assessment questionnaire-disability index (HAQ-DI) >= 0.25
• Stable doses of oral corticosteroids (CS) and/or maximum of 1 non-corticosteroid immunosuppressive/immunomodulatory medications (methotrexate, 6 mercaptopurine, sulfasalazine, mycophenolate mofetil or sodium, azathioprine, leflunomide, cyclosporine, oral tacrolimus) for DM or PM
• Participants have a body mass index (BMI) lower or Equal to 40.0 kilograms per square meter (kg/m^2)
• Other protocol defined inclusion criteria could apply
• Primary diagnosis of inclusion body myositis (IBM), malignancy-associated myositis (defined as diagnosis of myositis within 3 years of cancer), immune mediated necrotizing myopathy (IMNM) with a biopsy characterized as necrotizing biopsy or IMNM with positive anti-signal recognition particle antibody (SRP) or anti 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) auto antibodies. Participants with anti-transcription intermediary factor 1 (TIF1) gamma antibody or newly diagnosed (within 1 year) anti MDAT5 antibody should have had adequate screening for cancer within 12 months of Day 1. Adequate screening of cancer is defined as up-to-date age and gender appropriate screening as per national guidelines
• Primary diagnosis of juvenile DM, or adult participants previously diagnosed with juvenile DM
• Any other active concurrent connective tissue disease associated with inflammatory myopathy in the Investigator's opinion. Eligibility of participants with diagnosis of concurrent connective tissue disease(s) will be reviewed and approved by an idiopathic inflammatory myopathies (IIM) expert committee
• Severe interstitial lung disease defined as supplemental oxygen required at rest, or forced vital capacity (FVC) of <60 percent (%) predicted. Participants within 1 year of PM/DM diagnosis and anti-MDA5 antibody, should have been evaluated for interstitial lung disease (ILD) with high resolution computed tomography (HRCT) Chest
• Any uncontrolled disease (for example [e.g.], severe respiratory, cardiovascular, gastrointestinal, neurological, psychiatric, hematological, metabolic [including thyroiditis with increased/decreased thyroid stimulating hormone (TSH)], renal [Estimated glomerular filtration rate < 40 milliliter per minute/1.73 m^2 as calculated by the Modification of Diet in Renal Disease equation by the central laboratory], hepatic, endocrine/reproductive organ disease) other than DM/PM, that in the Investigator's or Sponsor/designee's opinion constitutes an inappropriate risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
• Other protocol defined exclusion criteria could apply
A Phase 1/2 Study of [225Ac]-FPI-1434 Injection
Pilot Study to Assess the Validity of Liquid Biopsy to Improve Diagnosis, Prognostic Assessment and Disease Monitoring in Patients Undergoing Liver Transplant for Hilar and Intrahepatic Cholangiocarcinoma
Pilot Study to Assess the Validity of "Liquid Biopsy" to Improve Diagnosis, Prognostic Assessment and Disease Monitoring in Patients Undergoing Liver Transplant for Hilar and Intrahepatic Cholangiocarcinoma
- Patients with perihilar or intrahepatic CCA undergoing liver transplant will be evaluated.
- Single lesion ≤3 cm.
- Absence of vascular invasion.
- No evidence of extrahepatic disease.
- No attempted prior resection with violation of tumor plane.
- General eligibility as a liver transplant candidate.
- No attempted prior resection with violation of tumor plane.
- None.
Blinded Comparison of Different Alpha-Synuclein Seeding Assays as Cutaneous Biomarkers of Lewy Body Dementias
Blinded Comparison of Different Alpha-Synuclein Seeding Assays as Cutaneous Biomarkers of Lewy Body Dementias
Inclusion Criteria:
- Males or females ≥ 40 years of age.
- Willingness to undergo the required clinical assessments and biopsies.
- Clinical diagnoses as DLB, PD and PDD.
- Are being treated with chemotherapy for cancer.
- Are known to have a structural brain lesion or other CNS disease process or symptoms.
- Have a clinically significant infectious disease, such as HIV, hepatitis or prion disease.
- Have suspected encephalopathy due to alcoholism or end-stage liver disease.
- Have a bleeding diathesis, are on anticoagulant therapy, or have severe medical illness.
- Have skin disease in the posterior cervical area.
OptimICE-PCR: De-Escalation of Therapy in Early-Stage TNBC Patients Who Achieve pCR After Neoadjuvant Chemotherapy With Checkpoint Inhibitor Therapy (OptimICE-pCR)
Pembrolizumab vs. Observation in People With Triple-negative Breast Cancer Who Had a Pathologic Complete Response After Chemotherapy Plus Pembrolizumab
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Triple Negative Breast Cancer:
- Patients with a history of stage T1cN1-2 or T2-4N0-2 breast cancer according to
the primary tumor-regional lymph node anatomic staging criteria of the American
Joint Committee on Cancer (AJCC), 8th edition as determined by the investigator
in radiologic assessment, clinical assessment or both
- Patients must have no residual invasive disease in the breast or lymph nodes
after the completion of neoadjuvant therapy. Residual ductal carcinoma in situ
(DCIS) is allowed. Isolated tumor cells are considered node-negative
- Estrogen (ER) and progesterone (PR) =< 10%; HER2-negative by American Society of
Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
(immunohistochemistry [IHC] and fluorescence in situ hybridization [FISH])
- If invasive disease was present in both breasts, participation in the study is
permitted as long as the eligibility criteria are met for both tumors/breasts
- Patients must have received neoadjuvant chemotherapy in combination with pembrolizumab
for a minimum of 6 cycles. All systemic chemotherapy and ICI therapy should have been
completed preoperatively
- An interval of no more than 12 weeks between the completion date of the final surgery
and the date of randomization
* Note: Adjuvant radiation can be given on study. If given, it is encouraged to be
given concurrently with pembrolizumab, per investigator discretion. Treatment with
adjuvant pembrolizumab is strongly discouraged prior to participation in this trial,
but if administered (e.g., if patients are awaiting pathology results), pembrolizumab
may be administered for up to 6 weeks post-surgery and must be completed prior to
registration
- Use of investigational anti-cancer agents must be discontinued at time of registration
- Adequate excision: Surgical removal of all clinically evident disease in the breast
and lymph nodes as follows:
- Breast surgery: Total mastectomy or breast-conserving surgery with histologically
negative margins, including no ink on tumor for DCIS, at the time of excision
** For patients who undergo breast-conserving surgery, the margins of the
resected specimen must be histologically free of ductal carcinoma in-situ (DCIS)
as determined by the local pathologist. If pathologic examination demonstrates
DCIS at the line of resection, additional operative procedures may be performed
to obtain clear margins. If DCIS is still present at the resected margin after
re-excision(s), the patient must undergo total mastectomy to be eligible.
Patients with margins positive for classic lobular carcinoma in situ (LCIS) are
eligible without additional resection
- Lymph node surgery:
- For a patient with clinically N0 disease, a sentinel lymph node biopsy
should have been performed at time of surgical evaluation, and if
pathologically node positive, the patient is no longer eligible. Isolated
tumor cells are considered node-negative
- For a patient with clinically N1 disease at diagnosis (with positive results
from a fine-needle aspiration, core biopsy, or sentinel node biopsy
performed prior to preoperative therapy) additional surgical evaluation of
the axilla following preoperative therapy is required
*** If they become cN0 (no palpable adenopathy), then a sentinel lymph node
biopsy could have been performed at time of surgery (axillary dissection
would also be permitted); if the sentinel lymph node biopsy is positive, the
patient is no longer eligible
- If sentinel node biopsy performed before preoperative therapy was negative,
no additional surgical evaluation of the axilla is required after
preoperative therapy. If sentinel node biopsy performed before preoperative
therapy was positive, an ALND is required after preoperative therapy
- If the only sentinel node identified by isotope scan is in the internal
mammary chain, surgical evaluation of the axilla is still required
- If sentinel node evaluation after preoperative therapy is negative, no
further additional surgical evaluation of the axilla is required
- Axillary dissection without sentinel node evaluation is permitted as the
initial or sole axillary evaluation after preoperative therapy
- If breast-conserving surgery was performed but patient will not be receiving breast
radiation, the patient is not eligible
- Not pregnant and not nursing, because this study involves an agent whose genotoxic,
mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
Therefore, for women of childbearing potential only, a negative serum or urine
pregnancy test done =< 7 days prior to randomization is required
- Absolute neutrophil count (ANC) >= 1,000/mm^3
- Platelet Count >= 100,000/mm^3
- Estimated glomerular filtration rate (eGFR) >= 15 mL/min/1.73m^2
- Total Bilirubin =< 1.5 x upper limit of normal (ULN)
* Patients with Gilbert's disease with a total bilirubin =< 2.5 x ULN and direct
bilirubin within normal limits are permitted
- Aspartate aminotransferase (AST) serum aspartate aminotransferase [SGOT] / alanine
aminotransferase (ALT) serum glutamic pyruvic transaminase [SGPT] =< 3 x institutional
ULN
- Patients must be willing to provide tumor tissue from the diagnostic core biopsy. If
inadequate tumor tissue is available, patients are still eligible to participate in
the trial
- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months prior to registration are
eligible for this trial
- No stage IV (metastatic) breast cancer
- No history of any prior (ipsi- or contralateral) invasive breast cancer. Prior DCIS is
allowed
- No evidence of recurrent disease following preoperative therapy and surgery
- No known active liver disease; e.g., due to hepatitis B virus (HBV), hepatitis C virus
(HCV), autoimmune hepatic disorders, or sclerosing cholangitis
- No history of intolerance, including Grade 3 or 4 infusion reaction or
hypersensitivity to pembrolizumab or murine proteins or any components of the product
* Note: Prior immune-related adverse events (irAEs) are allowed if they resolved and
the patient tolerated subsequent therapy without requiring chronic steroids for the
irAE
- No medical conditions that require chronic systemic steroids (>10 mg prednisone daily
or equivalent) or any other form of immunosuppressive medications and has required
such therapy in the last two years. Replacement therapy (e.g. thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
etc.) is not considered a form of systemic therapy
- Patients who are unable or unwilling to comply with the requirements of the protocol
per investigator assessment are not eligible
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 6/16/23. Questions regarding updates should be directed to the study team contact.
Pharmacokinetic profile of rosemary extract supplement
Rosemary Extract Supplement Pharmacokinetic
- Healthy subjects aged between 25 and 55 years.
- Non-smoker.
- Body Mass Index (BMI) between 20 and 30 kg/m^2.
- Any history or presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, endocrine, metabolic, hematological, neurologic, psychiatric, systemic or
infectious disease.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 12/7/23. Questions regarding updates should be directed to the study team contact.
Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of VE202 in Patients With Mild-to-Moderate Ulcerative Colitis
VE202 in Patients With Mild-to-Moderate Ulcerative Colitis
KEY INCLUSION CRITERIA
1. 18 to 75 years of age
2. Documented clinical and endoscopic diagnosis of UC at least 3 months prior to
randomization
3. Active mild to moderate UC, as defined by the following:
1. Disease that extends at least 15 cm from the anal verge
2. A modified Mayo score of 4 to 8 with: (i.) Mayo endoscopic subscore of ≥ 2 based
on screening flexible sigmoidoscopy; (ii.) Rectal bleeding score of ≥ 1
4. Has never received a biologic agent, Janus kinase inhibitor, or
sphingosine-1-phosphate modulator for the treatment of UC
5. If receiving corticosteroids, dose must be stable for at least 4 weeks before
randomization
6. Doses of other allowable UC medications must be stable for at least 8 weeks before
randomization
KEY EXCLUSION CRITERIA
1. Known history of Crohn's disease (CD) or indeterminate colitis
2. A known diagnosis of primary sclerosing cholangitis
3. Allergy to VE202 or any of its components
4. Allergy to vancomycin or any of its components
5. A diagnosis of any non-IBD diarrheal illness (eg, Clostridioides difficile, celiac
disease, parasitic infection) within 3 months prior to randomization
6. Use of probiotics or herbal, botanical, or traditional medicinal preparations within
the 2 weeks prior to randomization (consumption of food products such as yogurt,
kefir, kombucha, and herbal teas is permissible)
7. Receipt of Fecal Microbiota Transplantation (FMT) or other fecal-derived preparation
within 6 months prior to randomization
8. Prior colectomy, ostomy, or other intestinal surgery (excluding cholecystectomy or
appendectomy)
9. Receipt of any investigational biologic within 60 days or 5 half-lives prior to
randomization, whichever is longer
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 8/28/23. Questions regarding updates should be directed to the study team contact.
Safety and Efficacy of Tegoprubart in Patients Undergoing Kidney Transplantation
• Male or female ≥ 18 years of age
• Recipient of their first kidney transplant from a living or deceased donor
• Agree to comply with contraception requirements during and for at least 90 days after the last administration of study drug
• Induction therapy, other than study assigned rATG, planned as part of initial immunosuppressive regimen
• Currently treated with any systemic immunosuppressive regimen, including immunologic biologic therapies
• Currently treated with corticosteroids other than topical or inhaled corticosteroids
• Will receive a kidney with an anticipated cold ischemia time of > 30 hours
• Will receive a kidney from a donor that meets any of the following:
• 5a. Donation after Cardiac Death (DCD) criteria; Or
• 5b. Kidney Donor Profile Index (KDPI) of > 85%; Or
• 5c. Is blood group (ABO) incompatible
• Medical conditions that require chronic use of systemic corticosteroids or other immunosuppressants
• History of a thromboembolic event, known hypercoagulable state, or condition requiring long term anticoagulation
• Positive T- or B-cell crossmatch that is due to HLA antibodies or presence of a DSA at Screening
Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA)
• Acute focal symptoms or signs of any duration associated with imaging, pathological, or other objective evidence of arterial infarction OR clinical evidence of cerebral, spinal cord, or retinal focal arterial ischemic injury based on symptoms persisting greater than or equal to 24 hours that occurred within 30 days prior to randomization
• Index stroke is attributed to 70-99% stenosis (or flow gap on MRA) of a major intracranial artery (carotid artery, middle cerebral artery (M1 or M2), vertebral artery (V4), basilar artery, posterior cerebral artery (P1), or anterior cerebral artery (A1)) documented by CTA, MRA, or catheter angiography
• Modified Rankin Scale score of ≤ 4, at time of consent
• Ability to swallow pills
• At least 30 years of age, inclusive, at time of consent
• Subjects 30-49 years of age are required to meet at least ONE of the following additional criteria below to qualify for the study: 1. diabetes treated with insulin for at least 15 years 2. at least 2 of the following atherosclerotic risk factors: hypertension (BP > 140/90 or on antihypertensive therapy); dyslipidemia (LDL > 130 mg /dl or HDL < 40 mg/dl or fasting triglycerides > 150 mg/dl or on lipid lowering therapy); smoking; non-insulin dependent diabetes or insulin dependent diabetes of less than 15 years duration; any of the following vascular events occurring in a parent or sibling who was < 55 years of age for men or < 65 years of age for women at the time of the event: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery for atherosclerotic disease 3. personal history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease 4. any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by non-invasive vascular imaging or catheter angiography and is considered atherosclerotic 5. aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography 6. any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic
• Negative pregnancy test in a female who has had any menses in the last 18 months and has not had surgery that would make her unable to become pregnant
• Subject is willing and able to return for all follow-up evaluations required by the protocol
• Subject is available by phone
• Subject understands the purpose and requirements of the study and can make him/herself understood
• Subject has provided informed consent (use of a LAR is not permitted)
• Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, including mechanical thrombectomy for the qualifying stroke, or plan to perform one of these procedures
• Plan to perform concomitant endarterectomy, angioplasty or stenting of an extracranial vessel tandem to the symptomatic intracranial stenosis
• Intracranial tumor (except meningioma) or any intracranial vascular malformation
• Thrombolytic therapy within 24 hours prior to randomization
• Progressive neurological signs within 24 hours prior to randomization
• History of any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural)
• Intracranial arterial stenosis due to: arterial dissection; MoyaMoya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with CSF pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; postpartum angiopathy; suspected vasospastic process; reversible cerebral vasoconstriction syndrome (RCVS); suspected recanalized embolus
• Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, left atrial spontaneous echo contrast
• Known allergy or contraindication to aspirin, rivaroxaban, clopidogrel, or ticagrelor
• Uncontrolled severe hypertension (systolic pressure > 180 mm Hg or diastolic pressure > 115 mm Hg), active peptic ulcer disease, major systemic hemorrhage within 30 days prior to randomization, active bleed or bleeding diathesis, platelets < 100,000, hematocrit < 30, INR > 1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, severe liver impairment (AST or ALT > 3 x normal, cirrhosis), or CrCl < 15 mL/min or on dialysis
• Major surgery (including stenting of any vessel; open femoral, aortic, or carotid surgery; or cardiac surgery) within previous 30 days prior to randomization or planned in the next 90 days after randomization
• Any condition other than intracranial arterial stenosis that requires the subject to take any antithrombotic medication other than aspirin (NOTE: exceptions allowed for subcutaneous heparin for deep vein thrombosis (DVT) prophylaxis)
• Dementia or psychiatric problem that prevents the subject from following an outpatient program reliably
• Co-morbid conditions that may limit survival to less than 12 months
• Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study, or currently breastfeeding
• Current or anticipated concomitant oral or intravenous therapy with strong CYP3A4 inhibitors or CYP3A4 substrates that cannot be stopped for the course of this study
• Enrollment in another study that would conflict with the current study
Immune Control of Breast Cancer Tumor Dormancy
Immune Control of Breast Cancer Tumor Dormancy
Cohort A
- Females age 18-90
- Able to give informed consent
- Planned breast surgical procedure
- Biopsy proven invasive breast cancer
- Breast cancer of clinical estimated size of > 2 cm in diameter or biopsy proven node positive disease, diagnosed by percutaneous core needle biopsy
Cohort B
- Females age 18-90
- Able to give consent
- Planned breast surgical procedure
- Biopsy proven invasive breast cancer
- Treated with 4+ cycles of neoadjuvant chemotherapy
Cohort C
- Females age 18-90
- Able to give consent
- Planned breast surgical procedure
- Biopsy proven invasive breast cancer
- Clinical stage IV disease (metastatic breast cancer)
Cohort A
- Vulnerable subjects – pregnant women, children, prisoners, institutionalized individuals
- Benign breast disease
- Invasive cancer of < 2 cm in diameter and node negative
- Male patients
- Patients diagnosed with excisional or incisional biopsy
- Neoadjuvant endocrine or chemotherapy
- Platelet count of <150,000 plts/mcL (within 6 months)
Cohort B
- Vulnerable subjects – pregnant women, children, prisoners, institutionalized individuals
- Benign breast disease
- Male patients
- Patients diagnosed with excisional or incisional biopsy
- Neoadjuvant endocrine
- Platelet count of <150,000 plts/mcL (within 6 months)
Cohort C
- Vulnerable subjects – pregnant women, children, prisoners, institutionalized individuals
- Benign breast disease
- Male patients
- Platelet count of <150,000 plts/mcL (within 6 months)
MC200505 Phase II Study of Enfortumab Vedotin Treatment for Metastatic Squamous Cell Carcinoma of the Penis
A Study to Evaluate Enfortumab Vedotin to Treat Metastatic Squamous Cell Carcinoma of the Penis
- Male, aged 18 years or older on the day of consent.
- Histologically-proven squamous cell carcinoma of the penis.
- Stage:
- any T, N1 (i.e. a palpable mobile unilateral inguinal lymph node), M0 or;
- any T, N2 (i.e. palpable mobile multiple or bilateral inguinal lymph nodes), M0 or;
- any T, N3 (i.e. fixed inguinal nodal mass or any pelvic lymphadenopathy) M0;
- any T, any N, M1.
- Measurable disease as determined by RECIST (version 1.1) criteria.
- Patients may have received any number of prior anti-cancer treatments or be treatment naïve.
- Performance Status ECOG 0, 1 or 2.
- Required laboratory values:
- Absolute neutrophil count (ANC) ≥ 1.0/mcL
- Platelet count ≥ 100/mcL
- Hemoglobin ≥ 9 g/dL (transfusion of PRBCs allowed).
- Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease.
- Creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards or as measured by 24-hour urine collection (glomerular filtration rate [GFR] can also be used instead of CrCl).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
- Written informed consent.
- Pure verrucous carcinoma of the penis.
- Non-squamous malignancy of the penis.
- Squamous carcinoma of the urethra.
- Preexisting sensory or motor neuropathy ≥ Grade 2.
- Active central nervous system (CNS) metastases.
- Exception: Treated CNS metastases are allowed if all of the following are true:
- CNS metastases are clinically stable for ≥ 6 weeks prior to registration;
- If needed, steroid dose is stable and ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks prior to registration;
- Baseline imaging shows no evidence of new or enlarged brain metastasis;
- No leptomeningeal disease.
- History of uncontrolled diabetes mellitus ≤ 3 months prior to registration.
- NOTE: Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8.0% or HbA1c 7.0-7.9% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
- Any of the following prior therapies:
- Major surgery ≤ 4 weeks prior to registration;
- Radiotherapy, chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy ≤ 2 weeks prior to registration.
- Immunocompromised patients and patients known to be HIV positive.
- Uncontrolled intercurrent illness including, but not limited to:
- ongoing or active infection requiring systemic treatment;
- history of cerebral vascular event (stroke or transient ischemic attack);
- myocardial infarction or symptomatic congestive heart failure (NYHA Class III-IV) ≤ 6 months prior to registration;
- unstable angina pectoris;
- cardiac arrhythmia; or
- psychiatric illness/social situations that would limit compliance with study requirements (e.g., history of substance abuse).
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
- Currently receiving systemic antimicrobial treatment for viral, bacterial or fungal infection.
- NOTE: Routine antimicrobial prophylaxis is allowed.
- Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or active hepatitis C (e.g., hepatitis C virus [HCV] RNA [qualitative] is detected).
- Known active keratitis or corneal ulcerations.
- NOTE: Superficial punctate keratitis is allowed if the disorder is being adequately treated.
- Known hypersensitivity to enfortumab vedotin or to any excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate and polysorbate 20) OR subject has known hypersensitivity to biopharmaceutical produced in Chinese hamster ovary cells.
- Other active malignancy ≤ 2 years prior to registration.
- EXCEPTIONS: Locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, or carcinoma in situ of the breast or low risk Gleason 6 prostate cancer.
- History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
- Patients who are sexually active and unwilling to use effective contraception (if they are not already surgically sterile).
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
- Chemotherapy-naïve patients who are potentially curable (any T, N1 – N3, M0) in the absence of any condition that precludes cisplatin-based chemotherapy, such as low GFR, peripheral neuropathy, hearing impairment, or psychosocial considerations.
Multicenter Prospective Cohort Study on Current Treatments of Legg-Calvé-Perthes Disease (IPSG1)
Multicenter Prospective Cohort Study on Current Treatments of Legg-Calvé-Perthes Disease
- Diagnosed with Legg-Calvé-Perthes disease.
- Between 1-18 years of age.
- Patients with possible secondary femoral osteonecrosis if over the age of 11 due to trauma or corticosteroid therapy are also eligible.
- Patients with previous surgical treatment on the affected hip.
Eligibility last updated to match clinicaltrials.gov 7/22/22. Questions regarding updates should be directed to the study team contact.
Observational Registry study of Patients with Paroxysmal Nocturnal Hemoglobinuria treated with Pegcetacoplan
Paroxysmal Nocturnal Hemoglobinuria treated with Pegcetacoplan Patient Registry
- Enrolled in the core PNH registry or has PNH confirmed by high-sensitivity flow cytometry who will enroll in the core PNH registry.
- Currently receiving pegcetacoplan treatment.
- Patient or legally authorized representative are willing and able to provide written informed consent to participate in the pegcetacoplan PNH registry in a manner approved by the IRB/IEC and local regulations.
- Participating in an interventional PNH clinical trial.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 6/6/23. Questions regarding updates should be directed to the study team contact.
Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura (MAYARI)
• Is a woman of nonchildbearing potential (WONCBP), OR
• Is a woman of childbearing potential (WOCBP) and agrees to use an acceptable contraceptive method during the overall treatment period and for at least 2 months after the last study drug administration. Male participants with female partners of childbearing potential must agree to follow the contraceptive guidance as per protocol during the overall treatment period and for at least 2 months after last study drug administration.
• Clinical evidence of enteric infection with E. coli 0157 or related organism.
• Atypical HUS.
• Hematopoietic stem cell, bone marrow or solid organ transplantation-associated thrombotic microangiopathy.
• Known or suspected sepsis.
• Diagnosis of disseminated intravascular coagulation. Congenital TTP (known at the time of study entry). Clinically significant active bleeding or known co-morbidities associated with high risk of bleeding (excluding thrombocytopenia). Inherited or acquired coagulation disorders. Malignant arterial hypertension. Participants requiring or expected to require invasive procedures immediately (eg, stroke requiring thrombolytic therapy, those who need mechanical ventilation, etc.). Those presenting with severe neurological or cardiac disease. Clinical condition other than that associated with TTP, with life expectancy <6 months, such as end-stage malignancy. Known chronic treatment with anticoagulants and anti-platelet drugs that cannot be stopped (interrupted) safely, including but not limited to:
• vitamin K antagonists.
• direct-acting oral anticoagulants.
• heparin or low molecular weight heparin (LMWH).
• non-steroidal anti-inflammatory molecules other than acetyl salicylic acid. Participants who were previously enrolled in this clinical study (study EFC16521). Participants who received an investigational drug, or device, other than caplacizumab, within 30 days of anticipated IMP administration or 5 half-lives of the previous investigational drug, whichever is longer. Positive result on COVID test. The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
An Early Phase 1, Exploratory Study Evaluating 18F-Sodium Fluoride Positron Emission Tomography and Diffusion Magnetic Resonance Imaging to Assess Baseline Differences Between Adults with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Healthy Subjects, and Disease Progression in Adults with ADPKD
Evaluation of 18F-Sodium Fluoride Positron Emission Tomography and Diffusion Magnetic Resonance Imaging to Assess Baseline Differences Between Autosomal Dominant Polycystic Kidney Disease and Healthy Subjects, and Disease Progression in Adults with ADPKD
- Subject will sign and date an informed consent form (ICF).
- Willing and able to comply with scheduled visits, observation period, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
- Males and females between the ages of 18 and 60 years, inclusive.
- Body mass index (BMI) of 18.0 to 32.0 kg/m^2 , inclusive.
The following Inclusion Criteria apply to subjects in the healthy subject cohort:
- Healthy, as defined by no clinically relevant abnormalities identified by a detailed medical history, full physical examination (PE), including blood pressure and pulse rate measurement, standard 12 lead ECG, and clinical laboratory tests.
- eGFR ≥ 75 to < 120 mL/min/1.73 m^2 based on the Modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation without the race adjustment.
- Subjects will be matched during Screening to subjects in the ADPKD Cohort for age (± 5 years) and gender.
The following Inclusion Criteria apply to subjects in the ADPKD cohort:
- Diagnosis of ADPKD demonstrated by evidence of polycystic kidney disease in one or both biological parents and meeting Pei-Ravine classification noted below.
- Cysts must be > 2.5 mm in diameter and the minimum number of cysts present for each age category are as follows:
- Subjects < 40 years of age: ≥ 3 cysts in between both kidneys;
- Subjects ≥ 40 years of age: ≥ 2 cysts in each kidney.
- Cysts must be > 2.5 mm in diameter and the minimum number of cysts present for each age category are as follows:
- ADPKD subjects with Mayo Imaging Classification of 1C through of 1E.
- eGFR ≥ 45 to < 120 mL/min/1.73 m^2 based on the Modified CKD-EPI equation without the race adjustment.
- Subjects with metallic implants or medical conditions that are contraindicated with MRI.
- Previous significant exposure to ionizing radiation in the investigator’s opinion.
- History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk during the trial. This may include, but is not limited to, risk of compliance, mental disease, and history of cancer, except squamous cell skin cancer, basal cell skin cancer, stage 0 cervical carcinoma in situ (all 3 diagnosed ≥ 3 years ago with no recurrence in the past 3 years).
- Participated in research studies involving ionizing radiation.
- Subjects for whom participation in this study would lead to a yearly radiation exposure greater than the local radiation exposure recommendations.
- Females who are pregnant, nursing, or planning to become pregnant during the study.
- Use of substances, activities, or devices as indicated in Section 9.4 during the specified times.
- Subject, or close (first degree) relative of the subject, is the investigator or a subinvestigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study at that site.
- Uncontrolled hypertension, defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 95 mmHg.
- A diagnosis of cystic fibrosis.
- Ongoing or history of dialysis.
- History of solid organ or bone marrow transplant.
- Immediate genetic relative of an enrolled subject (parent, grandparent, or child).
- Currently enrolled in an interventional trial.
- Has taken tolvaptan or somatostatin analogues within the 12 weeks before Screening and has plans to start taking either of the medications during study participation.
- Previous history of renal cyst infection or ruptured cyst.
- Has had a renal cyst aspiration or fenestration within 12 weeks of Screening.
- Active diuretic use.
The following Exclusion Criterion applies to subjects in the healthy subject cohort:
- History of kidney disease that in the opinion of the investigator could confound study results, including but not limited to PKD, family history of PKD, congenital or acquired (cyst) anomalies of the kidney and urinary tract , previous nephrectomy, kidney stones, and recurrent urinary tract infections.
The following Exclusion Criteria apply to subjects in the ADPKD cohort:
- History of diabetes mellitus or history of kidney disease other than PKD;
- eGFR <45 mL/min/1.73 m^2 based on the modified CKD-EPI equation without the race adjustment.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 11/10/22. Questions regarding updates should be directed to the study team contact.
Treatment of LSCD With DM
• partial LSCD (involving less than 75% of the limbus, or <75% of the corneal surface)
• Visually significant (best-corrected visually acuity 20/100 or worse) Arm 2:
• total/near-total LSCD with recurrent erosions or PEDs (involving more than 75% of the limbus, or more than 75% of the corneal surface)
• Visually significant (best-corrected visually acuity 20/100 or worse) PLUS
• Persistent epithelial defects last >2 weeks despite maximal medical therapy OR
• Recurrent erosions occuring at least once every month
• Pregnant women
• Prisoners (vulnerable population)
• Adults lacking capacity to consent (vulnerable population)
• Adults unable to sign consent due to non-english speaking or illiterate (vulnerable population)
Home Alone: An Intervention for People With Cognitive Impairment Who Live Alone
• 55 years of age or older
• Lives alone in a non-residential setting
• Either 1) provider diagnosis of MCI, 2) Montreal Cognitive Assessment by telephone (T-MoCA) score between 13 and 18, and/or 3) subjective endorsement of memory impairment on screening
• Resides in the US
• Demonstrates capacity to consent
• Live in assisted living, a group care home, or similar residential setting that provides care and services
• Are not English speaking
• Are currently participating in any other type of service that provides one-to-one psychosocial consultation or independent living coaching
• Have a new or worsening mental health condition and are not receiving ongoing treatment
• Have not remained on a stable psychotropic medications dosage, such as antidepressants, anxiolytics, or anti-psychotics, for the prior three months
• Are not willing/interested in participating or cannot actively participate in the intervention, per researcher discretion
Quantification and distribution of Sulfated Glycosaminoglycan (sGAG) Adsorption on Retrieved TMJ Fossa Eminence Implants
Sulfated Glycosaminoglycan Adsorption on Retrieved TMJ Fossa Eminence Implants
- Undergoing TMJ metal fossa implant removal in the normal course of disease treatment.
- Subject refusal to participate.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 7/31/23. Questions regarding updates should be directed to the study team contact.
Comparison of the Fecal Microbiome among Patients with Multiple System Atrophy
Fecal Microbiome with Multiple System Atrophy
- Males or females aged 30-80 years.
- Participants who are willing and able to give informed consent.
- MSA patients fulfill Consensus Criteria for possible or probable MSA and diagnosed by a Mayo neurologist with MSA.
- PD patients diagnosed with PD by a Mayo neurologist.
- Healthy controls without evidence of neurologic disease or autonomic dysfunction.
- Environmental controls residing in the same household as MSA and PD patients.
- Pregnant or breastfeeding women.
- Participants with a clinically significant or unstable medical or surgical condition that, in the opinion of the investigator, might preclude safe completion of the study or might affect the results of the study.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 10/6/23. Questions regarding updates should be directed to the study team contact.
A Phase 1b/2 Dose Escalation and Expansion Study of the Combination of the Bispecific T Cell Redirection Antibodies Talquetamab and Teclistamab in Participants with Relapsed or Refractory Multiple Myeloma (RedirecTT-1)
A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma
- Documented initial diagnosis of multiple myeloma according to International Myeloma
Working Group (IMWG) diagnostic criteria.
- Part 1 and 2: Participant could not tolerate or has disease that is relapsed or
refractory to established therapies, including the last line of therapy. Part 3: (a)
Relapsed or refractory disease, and exposed to a PI, IMiD, and an anti-CD38 mAb; (b)
Documented evidence of progressive disease based on inve.stigator's determination of
response by IMWG criteria on or after their last regimen
Part 1 and Part 2:
- Eastern Cooperative Oncology Group (ECOG) performance status grade
of 0 or 1 at screening and immediately before the start of study drug administration.
Part 3: ECOG performance status grade of 0, 1, or 2 at screening and immediately
before the start of study drug administration.
All Parts:
- Targeted therapy, epigenetic therapy, or treatment with an investigational
treatment or an invasive investigational medical device within 21 days or at least 5
half-lives, whichever is less. Part 3: prior BCMA targeted bispecific antibody
therapy; prior GPRC5D targeted therapy.
- Allogeneic stem cell transplant within 6 months before the first dose of
study treatment.
- Central nervous system involvement or clinical signs of meningeal
involvement of multiple myeloma.
- Active plasma cell leukemia (greater than [>]2.0*10^9/L plasma cells by
standard differential), Waldenstro?m's macroglobulinemia, POEMS syndrome
(polyneuropathy, organomegaly, endocrinopathy, M- protein, and skin changes), or
primary amyloid light chain amyloidosis.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 10/2/23. Questions regarding updates should be directed to the study team contact.
Metabolic and Physiologic Responses to Hormone Therapy in Transgender and Gender Diverse People
Transgender Metabolic and Physiologic Responses to Hormone Therapy
- Transgender men and transgender women:
- Age 18-40yrs;
- BMI 18.5-38 kg/m^2;
- As well as a fasting glucose < 100 mg/dL;
- And with no gender affirming gonadal surgery.
- Pregnancy.
- Use of hormonal forms of birth control.
- Use of glucocorticoids, estradiol, testosterone, progestin, antiandrogens, or antiestrogens besides those received as part of a supervised hormone therapy.
- Gender-affirming gonadal surgery.
- Prior use of gonadotropin releasing hormone (GnRH) analogues during puberty.
- Coronary artery disease or heart failure.
- A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:
- Inpatient psychiatric treatment in the past 6 months;
- Presence of a known adrenal disorder;
- Abnormal liver function test results (Transaminase > 2 times the upper limit of normal); testing required for subjects taking medications known to affect liver function or with diseases known to affect liver function;
- Abnormal renal function test results (calculated GFR <45 mL/min/1.73m^2); testing required for subjects with diabetes duration of greater than 5 years post onset of puberty;
- Active gastroparesis;
- If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study;
- Uncontrolled thyroid disease (TSH undetectable or > 10 mlU/L); testing required within three months prior to admission for subjects with a goiter, positive antibodies, or who are on thyroid hormone replacement, and within one year otherwise;
- Abuse of alcohol or recreational drugs;
- Infectious process not anticipated to resolve prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis);
- Uncontrolled arterial hypertension (Resting diastolic blood pressure >90 mmHg and/or systolic blood pressure > 160 mmHg) at the time of screening.
- A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication, or disease in the judgment of the investigator will affect the completion of the protocol (exercise testing or muscle biopsy);
- Medications that may impact study end points such as mitochondrial biology; e.g., beta blockers;
- Anti-hyperglycemic drugs including metformin;
- Any other medication that the investigator believes is a contraindication to the subject’s participation.
Prevalence of C. albicans and other dysbiosis associated intestinal fungal dysbiosis in patients with eosinophilic asthma and non-eosinophilic asthma
Comparing Gut Bacterial and Fungal Microbiota Profiles of Different Asthma Phenotypes
- Adults ≥ 18 years of age.
- Confirmed diagnosis of chronic asthma (mild, moderate or severe).
- On maintenance therapy with an inhaled corticosteroid or ICS-LABA.
- Use of oral or IV antibiotic or antifungal medication within last 30 days.
- Previous or current treatment with asthma biologic therapy (mepolizumab, benralizumab, omalizumab, or dupilumab).
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 10/6/23. Questions regarding updates should be directed to the study team contact.
Human/Machine Interface: What the HeartMate 3 ® Device Tells Us About the Future
What the HeartMate 3 ® Device Tells Us About the Future
- 18 years of age or older.
- Scheduled Heartmate 3 ® dLVAD implantation.
Exclusion Critieria:
- < 18 years of age.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 5/16/23. Questions regarding updates should be directed to the study team contact.
Improved Training Method for Advanced Rehabilitation of Individuals with Lower Extremity Amputation (Rapid Rehab III)
Rapid Rehab III
- Research participants will be eligible active duty service members and retired veterans.
- Having lower limb trauma (transtibial and transfemoral amputations, bilateral amputations, and limb salvage).
- Are enrolled in conventional rehabilitation at the participating military treatment centers.
- Subjects with dysvascular disease will be excluded because compromised lower limb somatosensation and circulation are independently linked with poor postural stability and a history of frequent falls.
- For subjects with amputations, the individual must be a community ambulator (i.e., K-Level 3 or 4).
- For subjects with limb salvage, they will need to have an IDEO and be entered into the Return-to-Run training program.
- Subjects must not have excessive pain or other neuromuscular problems that preclude them from performing the test protocol.
Eligibility last updated 9/28/21. Questions regarding updates should be directed to the study team contact.
Safety, tolerability and dose limiting toxicity of lacosamide in patients with painful chronic pancreatitis. (STTEPP) (STTEPP)
Lacosamide in Patients With Painful Chronic Pancreatitis
- Written informed consent and HIPAA authorization for release of personal health information.
- ≥ 18 years old at the time of informed consent.
- Suspected (YELLOW 2 or 3) or definite diagnosis of CP, as per CPDPC PROCEED study definition with ongoing symptoms of abdominal pain.
- Patients must be maintained on an opioid (except methadone or suboxone) for 4 weeks prior to enrollment for treatment of abdominal pain related to pancreatitis, with a daily morphine equivalent dose of 20-120mg.
- Ongoing symptoms of abdominal pain even with opioid use (VAS and BPI average score ≥ 4, at enrollment).
- ECOG Performance Status of 0-2; (Oken et al., 1982).
- Ability to swallow and tolerate oral tablets.
- Females of childbearing potential must have a negative pregnancy test.
- The following laboratory parameters must be met: WBC count ≥ 3.0 K/mm^3, absolute neutrophil count ≥ 1.5 K/mm^3, hemoglobin ≥ 9 g/dL, platelets ≥ 75 K/mm^3, creatinine ≤ 1.5 mg/dl, bilirubin ≤ 1.5 x ULN, AST ≤ 3 ´ ULN, ALT ≤ 3 ´ ULN; normal PR interval on baseline 12-lead EKG.
- Subjects with indeterminate CP (YELLOW 1) as per PROCEED criteria.
- Treatment with any investigational agent within 30 days prior to registration, or concurrent participation in a clinical trial which involves another investigational agent.
- Rapidly escalating pain that requires hospitalization or intravenous opioid therapy.
- Known hypersensitivity/allergic reaction to lacosamide, carbamazepine or oxcarbazepine.
- Pregnant or breastfeeding.
- Patient who has a diagnosis of epilepsy and/or is currently taking anti-epileptic drugs.
- Abdominal surgery or pain intervention (ERCP with sphincterotomy/stent/stone removal; celiac plexus block) within 90 days of enrollment.
- Hospitalization for pancreatitis exacerbation or pain management within 90 days of enrollment.
- Patient who currently takes Suboxone, Methadone or uses Marijuana.
- Other factors which might explain the patient’s ongoing symptoms, at the discretion of the enrolling physician.
- History of autoimmune or traumatic pancreatitis, or sentinel attack of acute necrotizing pancreatitis which results in suspected disconnected duct syndrome.
- Primary pancreatic tumors- pancreatic ductal adenocarcinoma, suspected cystic neoplasm (> 1cms in size or main duct involvement), neuroendocrine tumors, and other uncommon tumors.
- Pancreatic metastasis from other malignancies.
- History of solid organ transplant, HIV/AIDS.
- Known isolated pancreatic exocrine insufficiency (e.g,. in the absence of any eligible inclusion criteria).
- Participants must not have medical or psychiatric illnesses or ongoing substance abuse that in the investigator’s opinion would compromise their ability to tolerate study interventions or participate in follow-up.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 10/4/22. Questions regarding updates should be directed to the study team contact.
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NST-6179 in Adult Subjects with Intestinal Failure-Associated Liver Disease (IFALD)
NST-6179 in Adult Subjects with Intestinal Failure-Associated Liver Disease
- Adult subjects aged 18 years or older at the time of informed consent.
- Agree to use appropriate contraceptive methods based on biological sex and child-bearing potential as outlined in Section 12.6.3 of the protocol.
- Agree to abstain from sperm or egg donation through 90 or 30 days, respectively, after administration of the last dose of IP.
- Able to understand the purpose and procedures that are involved in the study and willing to sign a written informed consent form and agrees to comply with the study protocol.
- Negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result obtained from test performed according to site standard of care between Day -3 and Day 1.
- Minimum of 6 months on PN supplementation as part of caloric needs prior to Visit 1 and plan to stay on PN therapy through the Treatment Period.
- Stable PN regimen for 4 weeks prior to and during the Screening Period. Stable regimen is defined as actual PN usage by volume and energy content and composition consistent with the prescribed regimen (± 10%).
- Willingness to maintain current habitual level of physical activity, oral diet, and lifestyle throughout the entire study.
- Part A and Part B: Established clinical diagnosis of IFALD based on a persistent elevation of liver enzymes (ALP, AST, ALT, or GGT ≥ 1.5 × upper limit of normal [ULN]) and/or total bilirubin > ULN for ≥ 6 months.
- Part B only: Presence of elevated ALP values ≥ 1.5 × ULN at Screening Visit 1.
- Part B only: Presence of hepatic steatosis defined as:
- Documented history of hepatic steatosis by liver ultrasound or FibroScan CAP ≥280 dB/m within 3 months of Screening Visit 1; or
- The presence of hepatic steatosis (>5% of hepatocytes) on liver histology within 6 months of Screening Visit 1; or
- FibroScan CAP ≥280 dB/m at Screening Visit 1. If FibroScan is performed during Screening Visit 1, this FibroScan can be used as the baseline measurement and does not need to be repeated at Baseline (Visit 3).
- Laboratory parameters consistent with stable liver disease without cirrhosis as defined by:
- ALT and AST < 5 × ULN;
- TBili ≤ 2.0 mg/dL in the absence of Gilbert’s Syndrome. i. Gilbert’s Syndrome patients are eligible as long as dBili is ≤ 0.5 mg/dL and ≤ 20% of the TBili level;
- Serum albumin ≥ 3 g/dL;
- International normalized ratio (INR) ≤ 1.3 in the absence of anticoagulant therapy;
- Platelet count ≥120,000/mm^3 .
- Intestinal surgery within 12 months of screening or planned during the Study Period.
- Use of feeding tubes for enteral feeding.
- Clinical, laboratory, imaging, or histopathologic evidence of other causes of acute or chronic liver disease, including autoimmune, viral, metabolic, or alcoholic liver disease.
- Clinical evidence of compensated or decompensated hepatic cirrhosis as assessed by historical liver histology, ultrasound-based and/or signs and symptoms of hepatic decompensation (including, but not limited to, jaundice, ascites, variceal hemorrhage, and/or hepatic encephalopathy).
- Presence of hepatic impairment, end-stage liver disease, and/or a model for end-stage liver disease (MELD) score > 12.
- History of solid organ transplant (except for corneal transplant) or planned transplantation during the Study Period.
- Laboratory parameters consistent with unstable or deteriorating liver function as defined by:
- ALP ≥ 10 × ULN;
- ALT and AST ≥ 5 × ULN;
- TBili > 2.0 mg/dL in the absence of Gilbert’s Syndrome.
- Gilbert’s Syndrome patients are eligible as long as dBili is ≤ 0.5 mg/dL and ≤ 20% of the TBili level.
- Transient elastography read >20.0 kPA within 3 months prior to or during the Screening Period.
- Estimated glomerular filtration rate < 45 mL/min based on the 2021 CKD-EPI creatinine equation (Inker, 2021).
- Human immunodeficiency virus (HIV), hepatitis A virus, hepatitis B virus, and/or hepatitis C virus infection, with the exception of those who have been successfully treated for hepatitis C infection and have achieved sustained virologic response for ≥ 1 year.
- History of malignancy within the past 5 years or ongoing malignancy other than basal cell carcinoma, resected noninvasive cutaneous squamous cell carcinoma, or treated cervical carcinoma in situ.
- Active infection that required antibiotic or antifungal therapy within 30 days before Screening Visit 1.
- Clinically significant ECG abnormalities, including, but not limited to, QT interval corrected for heart rate using Fridericia’s formula (QTcF) > 450 msec for males or > 460 msec for females at the Screening Visit (including Day -1) or prior to administration of the initial dose of IP.
- Introduction of Omegaven or other over-the-counter/off-label/investigational treatments for IFALD, including glucagon-like peptide-2 (GLP-2) analogues, in the past 3 months prior to Screening Visit 1. Subjects who are on a stable dose of Omegaven and/or Ursodeoxycholic acid or GLP-2 analogue for at least 12 weeks prior to Screening Visit 1 and still meet all other study criteria are allowed to enter the study.
- Currently receiving and expected to remain on treatment during the study with drugs which have drug-drug interactions with NST-6179.
- Treatment with steatogenic medications for ≥12 weeks in the past 12 months (eg, amiodarone, tamoxifen, methotrexate, tetracycline, glucocorticoids, anabolic steroids, an increase in the usual dose of estrogen for hormone replacement therapy, and valproate).
- Treatment with potential or known hepatotoxic medications that, in the judgement of the Investigator, is causing hepatic abnormalities.
- Any medication used for the treatment of an exclusionary medical condition.
- Hypersensitivity to NST-6719 (or to any of the excipients) or placebo.
- Pregnancy or breastfeeding.
- History of excessive alcohol or illicit drug use or abuse per the Investigator’s assessment.
- Positive urine drug screen at Screening unless the positive result is due to a medical treatment for a comorbid condition.
- Poor nutritional status defined as body mass index (BMI) <17 kg/m^2 .
- Recent or current catheter-related bloodstream infection (CRBSI) with the exception of those who have successfully been treated with antibiotics and CRBSI has been cleared as indicated by a negative blood culture at least 4 weeks prior to Screening Visit 1. Subjects with a history of recurrent CRBSI (3 or more CRBSIs within 2 years of Screening Visit 1) are also excluded.
- Recent or current small bowel bacterial overgrowth (SBBO) with the exception of those who have successfully been treated and cleared of SBBO at least 4 weeks prior to Screening Visit 1.
- Inability to swallow study medication for the duration of the study.
- Unwilling or unable to comply with the study protocol requirements.
- Has any other condition or prior therapy that, in the opinion of the Investigator, would impede competence or compliance or make the subject unsuitable for the study.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 3/22/23. Questions regarding updates should be directed to the study team contact.
Evaluation of human sera and cerebrospinal fluid from patients with autoimmune diseases (with and without autoantibodies) for laboratory based analyses
Laboratory Based Analyses of Human Sera and Cerebrospinal Fluid from Autoimmune Diseases With and Without Autoantibodies
- All ages.
- N/A.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 7/21/23. Questions regarding updates should be directed to the study team contact.
Achieving Equity through Socioculturally-informed, Digitally-Enabled Cancer Pain Management (ASCENT) - Main Trial
Collaborative Care Modle Based Intervention for Pain Contro in Rural Hispanic Cancer Survivors
Incusion Criteria:
- A qualifying liquid or solid cancer diagnosis with visits at a participating Mayo site.
- Age 18+.
- NRS pain score of a 5+ out of 10.
- Pain that developed (onset) or significantly worsened since cancer diagnosis.
- Malignant Hematology including:
- Lymphoma;
- Myeloma;
- Chronic Leukemias.
- PHQ8 score of 14 or more.
- Life expectancy less than 12 months.
- Hospice enrollment.
- SNF/Long term care placement.
- Acute Leukemias.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 8/14/23. Questions regarding updates should be directed to the study team contact.
Long COVID Ultrasound Trial (LOCUS)
A Study Comparing Talquetamab in Combination With Daratumumab or in Combination With Daratumumab and Pomalidomide Versus Daratumumab in Combination With Pomalidomide and Dexamethasone in Participants With Multiple Myeloma That Returns After Treatment or is Resistant to Treatment (MonumenTAL-3)
• Documented multiple myeloma as defined: a) Multiple myeloma diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria and b) Measurable disease at screening as defined by any of the following: i) Serum M-protein level greater than or equal to (>=) 0.5 grams per deciliter (g/dL) (central laboratory); ii) Urine M-protein level >= 200 milligram (mg) per 24 hours (central laboratory); iii) Light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin free light chain >= 10 milligram per deciliter (mg/dL) (central laboratory), and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Received at least 1 prior line of antimyeloma therapy including a proteasome inhibitor (PI) and lenalidomide. Participants who have received only 1 prior line of antimyeloma therapy must be considered lenalidomide-refractory (that is, have demonstrated progressive disease by IMWG criteria on or within 60 days of completion of lenalidomide-containing regimen). Participants who have received >=2 prior lines of antimyeloma therapy must be considered lenalidomide exposed
• Documented evidence of progressive disease based on investigator's determination of response by the IMWG criteria on or after their last regimen
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment
• Contraindications or life-threatening allergies, hypersensitivity, or intolerance to study drug excipients
• Disease is considered refractory to an anti-cluster of differentiation 38 (CD38) monoclonal antibody as defined per IMWG consensus guidelines (progression during treatment or within 60 days of completing therapy with an anti-CD38 monoclonal antibody)
• A maximum cumulative dose of corticosteroids to >=140 milligrams (mg) of prednisone or equivalent within 14-day period before the first dose of study drug
• Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are required
• Plasma cell leukemia (per IMWG criteria) at the time of screening, Waldenström's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS syndrome), or primary amyloid light chain amyloidosis