Impact of General Anesthesia vs. Moderate Sedation on Cognitive Function After LAOO: An Observational Study
Impact Of General Anesthesia Vs Moderate Sedation On Cognitive Function After LAAO
- Men and women ≥ 50 years of age.
- The patient has met eligibility criteria and is planned to undergo LAAO with the WATCHMAN FLX device as part of clinical care.
- The patient is able and willing to undergo non-invasive cognitive testing using the Viewmind headset by a trained personal.
- The patient is able to give informed consent for the procedure.
- The patient unwilling or unable to complete cognitive testing using the specialized virtual reality googles.
- Primary language is not English.
Eligibility last updated 3/11/22. Questions regarding updates should be directed to the study team contact.
Artificial Intelligence Enhanced Assessment of Speech Disorders: Prospective Data (NAIP-Speech)
Artificial Intelligence Enhanced Assessment of Speech Disorders
- Adult (18 years or older).
- Able to provide informed consent
- Able to provide samples in English.
- U.S. based patient.
- Age < 18 years of age.
- Unable to provide samples in English (i.e., need for interpreter flag in Epic).
- Nonverbal / No speech.
- HPP (High Profile Patient) status.
- International patient.
Eligibility last updated 3/3/22. Questions regarding updates should be directed to the study team contact.
A Phase 1/1b, Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and/or FGFR3 Gene Alterations
A Study to Evaluate KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and//or FGFR3 Gene Alterations
- Provide written informed consent prior to initiation of any study-specific procedures
- Advanced stage solid tumor
- Known FGFR2 and/or FGFR3 gene alteration, as confirmed by previous genomic analysis of
tumor tissue or ctDNA
- Measurable or evaluable disease according to RECIST v1.1
- ECOG performance status 0 or 1
- Adequate organ function, as measured by laboratory values (criteria listed in
protocol)
- Able to swallow, retain, and absorb oral medications
- Known clinically-active or clinically-progressive brain metastases from non-brain
tumors
- History and/or current evidence of abnormal calcium-phosphorous homeostasis, ectopic
mineralization or calcification, or corneal or retinal disorder/keratopathy
- GI tract disease causing an inability to take oral medication, malabsorption syndrome,
requirement for intravenous alimentation, or uncontrolled inflammatory GI disease
- Active, uncontrolled bacterial, fungal, or viral infection
- Women who are lactating or breastfeeding, or pregnant
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.
A Phase 1 Single Dose Escalation Study of PHIN-214 in Compensated and Decompensated Cirrhotic Patients (PharmaIN)
A Phase 1 Single Dose Escalation Study of PHIN-214 in Compensated Cirrhotic Patients
1. Body mass index within the range 18 to 40 kg/m2 (inclusive) at screening.
2. Females must be non-pregnant, non-lactating or of non-childbearing potential or using
highly efficient contraception for the full duration of the study.
3. Patients with liver cirrhosis confirmed by reliable biopsy (within 12 months) or
reliable Fibroscan >15 kPa at screening.
1. Significant abnormalities in medical history or on physical examination, including:
respiratory disease requiring therapy or history of respiratory failure,
cardiovascular disease or hypertension, electrocardiogram abnormalities or history of
significant EKG abnormalities.
2. History of diabetes insipidus, syndrome of inappropriate antidiuretic hormone
secretion, or any other disorder associated with fluid or sodium imbalance.
3. Significant kidney disease
4. Estimated glomerular filtration rate (eGFR by CKD-Epi) <60 ml/min/1.73 m2 or Cr >2.0
mg/dL.
5. Hepatic encephalopathy ≥ grade 1.
6. Recipient of a transjugular intrahepatic portosystemic shunt (TIPS).
7. Known positive HIV serology confirmed by HIV viral load.
8. Patients with acute hepatitis B; patients with known chronic hepatitis B are eligible
if treatment regimen is not changed in the 4 weeks prior to study inclusion
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 10/18/22. Questions regarding updates should be directed to the study team contact.
A Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for Metastatic HER2+ Breast Cancer (HER2CLIMB-05) (HER2CLIMB-05)
A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer
- Centrally confirmed HER2+ breast carcinoma per 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines.
- Have unresectable locally advanced or metastatic disease.
- If recurrent (after [neo]adjuvant therapy), must be at least 6 month treatment free from any trastuzumab or pertuzumab received for advanced HER2+ disease.
- Have received 4-8 cycles (21 day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression.
- Known hormone receptor status (per local guidelines; may be hormone receptor positive [HR+] or negative [HR-]).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 -CNS Inclusion.
- Based on screening contrast brain magnetic resonance imaging (MRI), participants may have any of the following:
- No evidence of brain metastases;
- Untreated brain metastases which are asymptomatic and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane;
- Previously treated brain metastases which are asymptomatic;
- Brain metastases previously treated with local therapy must not have progressed since treatment.
- Prior treatment with any anti-HER2 and/or anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and ≥ 12 months have elapsed since last neratinib dose prior to start of study drug).
- Unable to undergo contrast MRI of the brain -
CNS Exclusion:
- Based on screening brain MRI and clinical assessment.
- Symptomatic brain metastasis.
- Progression of brain metastases since starting first line trastuzumab, pertuzumab, and taxane.
- Ongoing use of systemic corticosteroids at a total daily dose of > 2 mg of dexamethasone (or equivalent).
- Any untreated brain lesion in an anatomic site which may pose risk to participant.
- Known or suspected leptomeningeal disease (LMD).
- Poorly controlled (> 1/week) seizures, or other persistent neurologic symptoms.
Eligibility last updated 2/28/22. Questions regarding updates should be directed to the study team contact.
A Phase 2 Study for the Evaluation of Safety and Efficacy of Humacyte’s Human Acellular Vessel for Vascular Replacement or Reconstruction in Patients with Life or Limb-threatening Vascular Trauma (CLN-PRO-V005)
Humacyte’s Human Acellular Vessel for Vascular Replacement or Reconstruction in Patients with Life or Limb-threatening Vascular Trauma
- Patients with life or limb threatening traumatic injury to an arterial vessel in the limb or torso, other than the heart, which requires replacement or reconstruction.
- Preoperative imaging or clinical examination indicates the damaged vessel has a defect length of ≤ 38cm and is appropriately size matched to the 6mm Human Acellular Vessel (HAV) per the judgment of the treating surgeon taking into account vasoconstriction and situational inflow and outflow considerations.
- Autologous vein graft is either not feasible in the judgment of the treating surgeon (e.g., because of lack of availability of suitable conduit, presence of severe venous insufficiency) or is not desirable because of the urgency of revascularization.
- Aged 18 to 85 years old, inclusive.
- Able to communicate meaningfully with investigative staff, and able to comply with entire study procedures. If the patient is unconscious, then information from a reliable witness indicates that the patient would normally be able to comply with study procedures.
- Patient or relative is able, willing and competent to give informed consent.
- Life expectancy of at least 1 year.
- Mangled Extremity Severity Score (MESS) of ≥ 7.
- Limb at high risk of amputation despite vascular reconstruction (e.g., because of crush injury).
- Catastrophic injuries that make survival unlikely (e.g., Abbreviated Injury Scale (AIS) > 5 or Injury Severity Score (ISS) > 60).
- HAV may not be used for coronary artery repair.
- Known pregnant women.
- Known medical condition which would preclude long term antiplatelet therapy after resolution of acute injuries.
- Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the HAV.
- Previous exposure to HAV.
- Known participation in any investigational study within the last 30 days.
- Employees of the sponsor or patients who are employees or relatives of the investigator.
Eligibility last updated 3/22/22. Questions regarding updates should be directed to the study team contact.
A Phase 0/Ia Study of BI 907828 Concentrations in Brain Tissue and a Non-randomized Open-label, Dose- escalation Study of BI 907828 in Combination with Radiotherapy in Patients with Newly-diagnosed Glioblastoma (BI 1403-0007)
A Study to Determine How BI 907828 is Taken up in the Tumor and to Determine the Highest Dose of BI 907828 That Could be Tolerated in Combination With Radiation Therapy in People With a Brain Tumor Called Glioblastoma
Inclusion Criteria
•Main Phase 0:
- Histologically (if prior biopsy) or radiologically diagnosed glioblastoma.
- Eligible for neurosurgical tumor resection.
- Patients must be at least 18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Adequate organ function.
- Life expectancy ≥ 3 months at the start of treatment in the opinion of the investigator.
Inclusion Criteria
•Main Phase Ia:
- Histologically demonstrated diagnosis of TP53 wild type glioblastoma harboring unmethylated MGMT promoters (Glioblastoma definition according to 2021 WHO Classification of CNS tumors; i.e., IDH-wild type only).
- Patient has undergone neurosurgical tumor resection and is eligible for standard radiotherapy.
- Formalin-fixed paraffin-embedded tumor blocks or representative H/E (haematoxylin/eosin) slides (preferably both) must be available for retrospective histopathological central review.
- Locally performed histopathological diagnosis will be accepted for entry into this trial.
- Patients must be at least 18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Adequate organ function.
- Life expectancy ≥ 3 months at the start of treatment in the opinion of the investigator.
Exclusion Criteria
•Main Phase 0:
- Known TP53 mutant glioblastoma.
- Note: testing is not mandatory for inclusion.
- Known IDH mutant grade IV astrocytoma.
- Note: testing is not mandatory for inclusion.
- Patients with pacemakers or other metallic implants that can interfere with the magnetic field during MRI investigations.
- Inability to undergo contrast-enhanced MRI (GFR < 30 mL/min).
Exclusion Criteria
•Main Phase Ia:
- Patients who have received previous systemic therapy (with the exception of patients who participated in Phase 0) or radiotherapy for glioblastoma.
- Patients with pacemakers or other metallic implants that can interfere with the magnetic field during MRI investigations.
- Inability to undergo contrast-enhanced MRI (GFR < 30 mL/min).
Eligibility last updated 3/1/22. Questions regarding updates should be directed to the study team contact.
A Phase 3 Randomized, Open-Label, Multicenter Clinical Study of CGT9486+Sunitinib vs. Sunitinib in Subjects With Locally Advanced, Unresectable, or Metastatic Gastrointestinal Stromal Tumors (CGT9486-21-301)
(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
1. Histologically confirmed locally advanced, metastatic, and/or unresectable GIST
2. Documented disease progression on or intolerance to imatinib
3. Have at least 1 measurable lesion according to mRECIST v1.1
4. ECOG
•0 to 2
5. Have clinically acceptable local laboratory screening results (clinical chemistry and
hematology) within certain limits
1. Prior treatment with < 2 Tyrosine Kinase Inhibitors (TKIs) (Part 1b only)
2. Prior treatment with any TKI other than imatinib (Part 2 only)
3. Known PDGFR alpha D842V mutation or known succinate dehydrogenase deficiency
4. Clinically significant cardiac disease
5. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study
drug
6. Gastrointestinal abnormalities including, but not limited to, significant nausea and
vomiting, malabsorption, external biliary shunt, or significant bowel resection that
would preclude adequate absorption
7. Any active bleeding excluding hemorrhoidal or gum bleeding
8. Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis
C virus (HCV) antibody.
9. Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
10. Received strong CYP3A4 inhibitors or inducers
11. Received sunitinib within 3 weeks (Part 1a, Part 1b)
Efficacy of the COronary SInus Reducer in Patients With Refractory Angina II (COSIRA-II) (COSIRA-II)
Efficacy of the COronary SInus Reducer in Patients With Refractory Angina II
1. Subject is older than 18 years of age
2. Symptomatic coronary artery disease (CAD) with greater than or equal to 90 days of
persistent refractory angina pectoris classified as CCS Grade III or IV despite
maximally tolerated guideline directed medical therapy as determined by the local
heart team and confirmed by a Central Screening Eligibility Committee.
Note: subjects may also have exertional dyspnea, but the symptoms that limit activity
must be anginal in nature (including chest pain, pressure, heaviness, discomfort, with
or without radiation to the neck, jaw, shoulders, arms, or other location) and not
dyspnea
3. Must have attempted treatment with the maximally tolerated dose of at least three of
the four (preferably all four) approved classes of anti-anginal agents: long-acting
nitrates, calcium channel blockers (either a dihydropyridine or a
non-dihydropyridine), beta blockers, and ranolazine. The regimen must be stable for at
least 60 days prior to enrollment, must remain stable from enrollment to
randomization, and there must be no intent to change the medical regimen for at least
12 months after randomization Note: If the dose of a medication was increased or
decreased for a temporary period and then returned to the original dose, which will
then be continued for at least 12 months after randomization, the subject may be
immediately enrolled without needing to otherwise requalify.
4. Subject has either no treatment options for revascularization by coronary artery
bypass grafting or by percutaneous coronary intervention, or is otherwise unsuitable
or high risk for revascularization as determined by the local heart team, and
confirmed by a Central Screening Eligibility Committee
5. Evidence of either exercise or pharmacologically induced reversible ischemia severity
by stress echo, nuclear study, PET, perfusion MRI, CT perfusion, FFRCT, FFR, iFR, or
other non-hyperemic FDA approved tests in the distribution of the left coronary artery
(LCA), performed within 12 months prior to enrollment and while the patient is
maintained on their stable regimen of maximally tolerated doses of anti-anginal
medications.
Note: If the subject has evidence of ischemia in both the LCA and RCA distributions,
the extent of ischemia must be greater in the LCA distribution.
Note: The qualifying assessment must be performed after any myocardial infarction,
CABG, or successful PCI within the prior 12 months. If the anti-anginal medication
regimen is permanently changed after the assessment of ischemia, the test must be
repeated. For subjects with multiple assessments, the one performed closest to
enrollment will serve as the qualifying study.
6. Functional limitation due to refractory angina as defined by a modified Bruce exercise
tolerance test duration of greater than or equal to 2 minutes but less than or equal
to 8 minutes, performed while the subject is maintained on their stable regimen of
maximally tolerated doses of anti-anginal medications.
Note: The ETT variability must be less than 20% between last two ETTs performed.
7. Left ventricular ejection fraction (LVEF) greater than or equal to 30% within the
12-months prior to enrollment Note: The LVEF must be reassessed after any intervening
myocardial infarction. For subjects with multiple assessments, the most recent LVEF
assessment is used as the qualifying test.
8. Subject is willing and able to sign informed consent
9. Subject is willing to comply with the specified follow-up evaluations
Angiographic
1) Three-vessel coronary angiography performed within 12 months prior to enrollment
demonstrating obstructive CAD (visually estimated diameter stenosis of ≥70% or ≥50%
•<70%
with fractional flow reserve (FFR) value of ≤0.80 or an iFR or other FDA-approved/cleared
non-hyperemic physiological assessment of ≤0.89 in one or more lesions) in the left
coronary artery (main epicardial vessels or branches) that is not suitable for and will not
be treated with PCI or CABG as determined by the local heart team.
Note: The qualifying 3-vessel angiogram must be performed after any myocardial infarction
or CABG within the 12 months prior to enrollment. For patients with multiple 3-vessel
angiograms, the one performed closest to enrollment will serve as the qualifying study.
1. Recent (within 30 days prior to enrollment) troponin or CKMB positive acute coronary
syndrome (NSTEMI or STEMI).
Note: subjects with an elevated troponin or CKMB without acute coronary syndrome may
still be enrolled
2. Recent successful revascularization by either CABG or PCI within six months prior to
enrollment Note: Successful revascularization is defined as any CABG procedure, or any
PCI procedure with a reduction of one or more lesions to <50% diameter stenosis
3. Recent unsuccessful PCI (e.g., failed attempt to open a chronic total occlusion)
within 30 days prior to enrollment
4. The predominant manifestation of angina is dyspnea. Note: some dyspnea may be present
with exertion, but the predominant symptom that limits activity must be angina (i.e.,
chest pain, pressure, tightness, heaviness, or discomfort, with or without radiation
to the neck, jaw, shoulders, arms, or other location)
5. Has extra-coronary contributory causes of angina
•e.g., untreated hyperthyroidism,
anemia (hgb <10 g/dL), uncontrolled hypertension (systolic blood pressure >160 mmHg or
diastolic blood pressure >100 mmHg despite medications), atrial fibrillation with
rapid ventricular response (consistently >100 bpm despite medications) or other
tachyarrhythmia, severe aortic stenosis, hypertrophic cardiomyopathy with left
ventricular outflow tract obstruction or asymmetric septal hypertrophy (concentric
left ventricular hypertrophy is not an exclusion criterion).
6. NYHA Class III or IV heart failure (HF), decompensated HF or hospitalization due to HF
during the 90 days prior to enrollment
7. Life threatening rhythm disorders or any rhythm disorders that would require future
placement of an internal defibrillator and/or pacemaker
8. Severe chronic obstructive pulmonary disease (COPD) as indicated by a forced
expiratory volume in one second (FEV1) that is less than 55% of the predicted value,
or need for home daytime oxygen or oral steroids
9. Severe valvular heart disease (any valve)
10. Moderate or severe RV dysfunction by echocardiography
11. Pacemaker electrode/lead is present in the coronary sinus
12. A Class I indication is present for an implantable defibrillator or cardiac
resynchronization therapy according to ACCF/AHA/HRS guidelines
13. Recent implantation of a new pacemaker or defibrillator lead with electrode in the
right atrium within 90 days of enrollment
14. Chronic severe renal failure (estimated eGFR less than 30 mL/min/1.73m2 by the MDRD
formula) or subjects on chronic dialysis
15. Known allergy to stainless steel or nickel
16. Any clinical condition that might interfere with the trial protocol or the subject's
ability to be compliant with the trial protocol (e.g., active alcohol or drug abuse,
dementia, magnetic resonances imaging (MRI) planned within 8 weeks of randomization.)
17. Currently enrolled in another investigational device or drug trial that has not
reached its primary endpoint or that might clinically interfere with the current trial
endpoints or procedures
18. Pregnant or planning pregnancy within the next 12 months (women of reproductive
potential must have a negative pregnancy test within 7 days of the randomization
procedure)
19. Subject is part of a vulnerable population who, in the judgment of the investigator,
is unable to give Informed Consent for reasons of incapacity, immaturity, adverse
personal circumstances or lack of autonomy. This may include individuals with mental
disability, persons in nursing homes, children, impoverished persons, persons in
emergency situations, homeless persons, nomads, refugees, and those incapable of
giving informed consent. Vulnerable populations also may include members of a group
with a hierarchical structure such as university students, subordinate hospital and
laboratory personnel, employees of the Sponsor, members of the armed forces, and
persons kept in detention.
20. Inability to tolerate dual antiplatelet therapy for 6 months if not on a chronic oral
anticoagulant, or inability to tolerate a P2Y12 inhibitor for at least 6 months if on
a chronic oral anticoagulant
21. Comorbidities limiting life expectancy to less than one year
22. Subject is currently hospitalized for definite or suspected COVID-19
23. Subject has previously been symptomatic with or hospitalized for COVID-19 and has been
asymptomatic for <8 weeks prior to enrollment or has not returned to his or her prior
baseline (pre-COVID-19) clinical condition
24. Subject is asymptomatic but has had a positive PCR or antigen test for COVID-19 within
the past 4 weeks prior to enrollment
Angiographic/Hemodynamic
1) Coronary anatomy amenable to revascularization of ischemic myocardial territory by
either PCI or CABG with at least moderate likelihood of long-term alleviation of angina or
angina equivalent symptoms, as per the assessment of the local heart team.
Note: If a pathway to coronary revascularization is present which, in the opinion of the
local heart team, is reasonably low risk and reasonably likely to provide long-term symptom
relief and the subject refuses the revascularization procedure, the patient is ineligible
for randomization
Procedural Angiographic/Hemodynamic Randomization
1. Mean right atrial pressure greater than 15 mmHg assessed during the final screening
procedure for eligibility assessment and potential randomization
2. Anomalous or abnormal CS anatomy (e.g., tortuosity, aberrant branch, persistent left
superior vena cava [SVC]) as demonstrated by angiogram
3. The CS diameter at the most proximal end of the planned implant region (2-4 cm distal
to the coronary sinus ostium) is less than 9.5 mm or greater than 13.0 mm
Single Arm Registry
The subject must meet all inclusion and exclusion criteria for the main randomized trial,
except for three possible specific conditions as follows:
1. Subjects with evidence of either exercise or pharmacologically induced reversible
ischemia by stress echo, nuclear study, PET, perfusion MRI, CT perfusion, FFRCT, FFR,
iFR, or other non-hyperemic FDA approved or cleared tests in the predominate (RCA >
LCA ischemia) or sole distribution of the right coronary artery
2. Subjects with evidence of either exercise or pharmacologically induced reversible
ischemia by stress echo, nuclear study, PET, perfusion MRI, CT perfusion, CFR, or IMR
without documented obstructive coronary disease (i.e. estimated diameter stenosis in
all coronary lesions is <50%)
3. Subjects who are unable to complete the required COSIRA-II exercise tolerance test due
to lower limb amputation (above the ankle).
Single-Arm Registry Angiographic Inclusion Criteria
1. Obstructive CAD: Three-vessel coronary angiography performed within the 12 months
prior to enrollment demonstrating obstructive CAD (visually assessed diameter stenosis
of ≥70%) in the RCA if it is single vessel disease, or the ischemia in the territory
of the RCA is greater than the ischemia in the territory of the LCA when it is >2
vessel coronary disease, or a fractional flow reserve (FFR) value of ≤0.80 or an iFR
(or other FDA-approved/cleared non-hyperemic physiologic assessment) of ≤0.89 in an
RCA lesion with a visually assessed diameter stenosis of ≥50% in single RCA coronary
disease, that is not suitable for and will not be treated with PCI or CABG as
determined by the local heart team.
2. Non-obstructive CAD: Patients with non-obstructive CAD (coronary narrowing of <50%,
and/or FFR ≥0.81) Note: The qualifying 3-vessel angiogram must be performed after any
myocardial infarction or CABG within the 12 months prior to enrollment. For patients
with multiple 3-vessel angiograms, the one performed closest to enrollment will serve
as the qualifying study.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 4/18/23. Questions regarding updates should be directed to the study team contact.
Mayo Clinic Digital Menopause Management Study
Testing of a Menopause Management Digital Health Application
- Adult postmenopausal women, aged 45-60 years.
- Menopause symptoms (hot flashes/night sweats) rated moderate or greater or total MRS score ≥ 14.
- Current use of hormone therapy.
Eligibility last updated 3/10/22. Questions regarding updates should be directed to the study team contact.
Tiered Inpatient Telemetry - Validation
Tiered Inpatient Telemetry
- Age 18+.
- Capable of consenting.
- Actively being monitored on Philips inpatient telemetry.
- Under the age of 18.
- Unable to consent.
- Pregnant patients.
Eligibility last updated 4/21/22. Questions regarding updates should be directed to the study team contact.
A Phase 1, Open-Label, Dose-Escalation and Expansion Study of the Bruton Tyrosine Kinase-Targeted Protein-Degrader BGB-16673 in Patients With B-Cell Malignancies
A Phase 1 Dose-Escalation and Expansion Study of BGB-16673 in Patients With B-Cell Malignancies
Inclusion Criteria :
1. Provision of signed and dated written informed consent prior to any study-specific
procedures, sampling, or data collection
2. Age ≥ 18 years
3. Confirmed diagnosis (per World Health Organization [WHO] guidelines, unless otherwise
noted) of one of the following: MZL (Part 1a and 1b only), FL (Part 1a only), MCL,
CLL/SLL, WM (Part 1a and 1b only), DLBCL (Part 1a only), or >2 treatments per the
Richter's transformation to DLBCL (Part 1a only).
4. Patients who have previously received a covalently-binding BTK inhibitor in any line
of therapy must have received treatment with the BTK inhibitor for ≥ 8 weeks (unless
reason for discontinuation is intolerance).
5. For dose-finding and dose-expansion, patients who had previously received a
covalently-binding BTK inhibitor as monotherapy or in combination with other
anticancer agents are eligible for the study if they meet any of the following
criteria: discontinued the previous BTK inhibitor due to disease progression,
experienced disease progression after completing treatment with a BTK inhibitor or
discontinued the BTK inhibitor due to toxicity or intolerance.
6. Measurable disease by radiographic assessment or serum IgM level (WM only)
7. ECOG Performance Status of 0 to 2
8. Patients enrolling in the dose finding phase of the study may be previously treated
with a BTKi or may be naïve to BTKi therapy depending on the diagnosis and country of
enrollment; patients with CLL/SLL or MCL enrolling in the expansion cohorts (Part 2)
must have been treated with a BTKi in a prior line of therapy.
1. Prior malignancy (other than the disease under study) within the past 2 years, except
for curatively treated basal or squamous skin cancer, superficial bladder cancer,
carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate
cancer
2. Requires ongoing systemic treatment for any other malignancy
3. Requires ongoing systemic (defined as ≥ 10 mg/day of prednisone or equivalent)
corticosteroid treatment.
4. Current or history of central nervous system involvement including the brain, spinal
cord, leptomeninges, and cerebrospinal fluid (as documented by imaging, cytology, or
biopsy) by B-cell malignancy, regardless of whether patient had received treatment for
central nervous system disease
5. Known active plasma cell neoplasm, prolymphocytic leukemia, T-cell lymphoma, Burkitt
lymphoma, acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, Castleman
disease, post-transplant lymphoproliferative disorders, hairy cell leukemia, GCB
DLBCL, EBV+ DLBCL NOS, primary DLBCL of the central nervous system (CNS), primary
cutaneous DLBCL
•leg type, DLBCL associated with chronic inflammation, primary
mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, ALK+
large B-cell lymphoma, primary effusion lymphoma, high-grade B-cell lymphoma with MYC
and BCL2 and/or BCL6 rearrangements, high-grade B-cell lymphoma
•NOS, B-cell lymphoma
unclassifiable with features intermediate between DLBCL and classical Hodgkin
lymphoma, or history of or currently suspected Richter's transformation of an indolent
lymphoma to an aggressive histology (only patients with Richter Transformation to
DLBCL are eligible for Part 1a).
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 5/19/23. Questions regarding updates should be directed to the study team contact.
REstrictive versus LIberal Rate of Extracorporeal Volume Removal Evaluation in Acute Kidney Injury ( RELIEVE-AKI)
REstrictive versus LIberal Rate of Extracorporeal Volume Removal Evaluation in Acute Kidney Injury (RELIEVE-AKI)
- Age ≥ 18 years.
- Stage 3 acute kidney injury according to the KDIGO criteria.
- Started or intending to start CKRT for volume management.
- Attending intensivist or nephrologist intending to remove fluid using CKRT for at least 48 hours.
- Respiratory distress due to pulmonary edema or fluid overload.
- Massive volume infusion (i.e., > 200 mL/h for > 6 hours of continuous infusion).
- No intention to remove fluid as determined by attending intensivist or nephrologist.
- Attending intensivist or nephrologist believes that the protocol will not be followed.
- Continuous fluid removal for > 24 hours prior to study enrollment.
- Actual or estimated premorbid body weight > 120 kilograms.
- Patients treated with intermittent hemodialysis during the current admission.
- Patients on chronic outpatient hemodialysis.
- Patients with history of, or current admission for kidney transplantation.
- Do not resuscitate, intubate, or comfort measures only orders (i.e., DNR/DNI/CMO).
- Moribund not expected to survive > 24 hours.
- Confirmed pregnancy.
- Patients treated with extracorporeal membrane oxygenation (ECMO), ventricular assist device (VAD), or intra-aortic balloon pump (IABP).
- Organ donors with neurological determination of death (i.e., brain dead donors).
- Drug overdose requiring CKRT.
- Enrollment in a concurrent interventional clinical trial with direct impact on fluid balance (e.g., > 500 mL study drug administration).
Eligibility last updated 3/9/22. Questions regarding updates should be directed to the study team contact.
Evaluation of C-Scan Capsule in Identifying Subjects With Elevated Risk of Colon Polyps
Evaluation of C-Scan Capsule in Identifying Subjects With Elevated Risk of Colon Polyps
1. Subjects 45-75 years old
2. Able to provide a signed informed consent.
3. Willing and able to comply with the specified study requirements and can be contacted
by telephone.
4. Scheduled for colonoscopy procedure no later than 60 days after C-Scan ingestion
5. Maximal abdominal circumference < 125 cm.
1. Subject who is not a suitable candidate for a colonoscopy
2. Known history of dysphagia or other swallowing disorders.
3. History of the following:
1. Colorectal polyps
2. A personal history of CRC
3. A family history of CRC or adenomatous polyps diagnosed in a relative before 60
years of age
4. A history of inflammatory bowel disease of significant duration
5. One of two (2) hereditary syndromes
4. Known motility disorders:
1. Chronic Constipation: less than three (3) bowel movements/week, without the use
of laxatives within the last 3 months.
2. Ongoing diarrhea defined as passage of loose or watery stools at least three
times within 24-hour
3. Delayed gastric emptying.
5. Known IBD (Crohn's, Ulcerative Colitis)
6. Prior history of gastrointestinal tract surgery.
7. Prior history of abdominal surgery that might cause bowel strictures leading to
capsule retention, as determined by a physician
8. Any condition believed to have an increased risk for capsule retention, known
strictures, known bowel adhesion or 'obstacles' to free passage of the capsule (such
as esophageal diverticulosis, intestinal tumors, radiation enteritis) or incomplete
colonoscopies as determined by a physician.
9. Significant change in diameter and frequency of stool within the last 3 months.
10. GI bleeding within the last 3 months i.e., rectal outlet bleeding, hematochezia or
melena.
11. Implanted cardiac device or any other implanted active device
12. Known sensitivity to iodine
13. Acute kidney failure
14. Known condition which precludes compliance or is contraindicated with study and/or
device instructions.
15. Any procedure requiring contrast agent, or which may introduce electronic interference
(such as magnetic resonance imaging, DEXA scan) or an imaging procedure pre-scheduled
within 14 days of C-Scan ingestion
16. Nuclear imaging procedure within the four (4) weeks preceding the C-Scan procedure.
17. Known condition of opioid use disorder and/or alcoholism.
18. Women who are either pregnant or nursing at the time of screening (to be verified by
urine or serum pregnancy test for woman of child- bearing potential who are not
post-menopausal or undergone surgical sterilization).
19. Concurrent participation in another clinical trail using any investigational drug or
device.
20. Previous colonoscopy performed five (5) years or less before date of enrolment
21. Subjec
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 1/25/23. Questions regarding updates should be directed to the study team contact.
ts who tend to hyperhidrosis in the back area
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Multicenter Study of Itolizumab in Combination With Corticosteroids for the Initial Treatment of Acute Graft Versus Host Disease
A Study of Itolizumab in Combination With Corticosteroids for the First-Line Treatment of Acute Graft Versus Host Disease (EQUATOR)
1. Is willing and able to provide written informed consent/assent and to comply with all
protocol procedures and assessments required for the study.
2. Is age ≥ 12 years and > 40kg at informed consent/assent.
3. Has had an initial allogeneic HSCT for any indication using any graft source, donor
source, conditioning regimen intensity or prophylaxis.
4. Has evidence of myeloid engraftment
5. Has a clinical diagnosis of aGVHD Grades III-IV or Grade II with LGI involvement based
on Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria.
6. Began systemic corticosteroid treatment for aGVHD ≤72 hours prior to the start of
study drug dosing AND must receive 2 mg/kg/day methylprednisolone or equivalent on Day
1. Evidence of morphological relapsed, progressive, persistent, or untreated malignancy,
with the exception of nonmelanoma skin cancer and in situ ductal carcinoma of the
breast.
2. An unplanned donor lymphocyte infusion for persistent or recurrent malignancy after
HSCT.
3. Evidence of persistent molecular disease requiring treatment that was not specified
prior to HSCT.
4. Evidence of cGVHD or overlap syndrome
5. Use of immunosuppressants other than corticosteroids for the treatment of aGVHD.
6. Use of any systemic corticosteroids of > 0.5 mg/kg/day methylprednisolone or equivalent
for any indication other than aGVHD within 7 days before the onset of aGVHD.
Eligibility last updated 7/19/22. Questions regarding updates should be directed to the study team contact.
A Phase 3b, Multicenter, Randomized, Double-blind Extension Study to Evaluate the Continued Efficacy and Safety of Oral Edaravone Administered for an Additional Period of up to 48 Weeks Following Study MT-1186-A02 in Subjects With Amyotrophic Lateral Sclerosis (ALS)
Efficacy and Safety Extension Study of Oral Edaravone Administered in Subjects With ALS
1. Subjects or their legally authorized representative must provide a signed and dated
informed consent form to participate in the study.
2. Subjects must be able (in the judgment of the Investigator) to understand the nature
of the study and all risks involved with participation in the study.
3. Subjects must be willing to cooperate and comply with all protocol restrictions and
requirements.
4. Subjects must have successfully completed all Study MT-1186-A02 visits and have been
compliant with study drug.
1. Subjects of childbearing potential unwilling to use an acceptable method of
contraception from the Day 1/screening visit until 3 months after the last dose of
study medication. Subjects who are sexually active who do not agree to use
contraception during the study period.
2. Subjects who are female, of childbearing potential, and pregnant (a positive pregnancy
test) or lactating at the Day 1/screening visit.
3. Subjects who have a significant risk of suicide. Subjects with any suicidal behavior
or suicidal ideation of type 4 (active suicidal ideation with some intent to act,
without a specific plan) or type 5 (active suicidal ideation with specific plan and
intent) based on the Columbia-Suicide Severity Rating Scale (C-SSRS) at Week 48 of
Study MT-1186-A02.
4. Subjects who are not eligible to continue in the study, as judged by the Investigator
in conjunction with the MTDA medical monitor.
5. Subjects who are unable to take their medications orally or through a PEG/RIG tube.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 12/6/22. Questions regarding updates should be directed to the study team contact.
Furthering Our Understanding of Neurovascular Function in Women with Uterine Fibroids
Neurovascular Function in Women with Uterine Fibroids
- Premenopausal women, ages 18-50 years old.
- Uterine fibroid group (n≈20): These participants will have had a previous or current diagnosis of UF determined by ultrasound, hysteroscopy, or MRI, confirmed with medical documentation within one year of recruitment.
- Control (non-fibroid) group (n≈20): These participants will not have evidence of UF (confirmed by imaging) at the time of study participation.
- History or evidence of:
- hepatic, renal, or hematological disease;
- peripheral vascular disease;
- stroke/neurovascular disease;
- diabetes;
- dyslipoproteinemia;
- hypertension (> 130/80 mmHg brachial cuff pressure);
- lung disease;
- arthritis affecting ability to exercise; or
- a body mass index > 30 kg/m^2.
- Participants also will be excluded if taking antihypertensive medication or medication that alters autonomic or vascular function (e.g., tricyclic antidepressants, alpha-blockers, beta-blockers, etc.).
- Participants will be non-smokers.
- Subjects must have a negative pregnancy test in order to participate in the study.
- Participants who are breastfeeding will be excluded.
- Women who have undergone hysterectomy will be excluded.
Eligibility last updated 3/7/22. Questions regarding updates should be directed to the study team contact.
A Multicenter, Open-Label, Extension Trial to Investigate Long Term Efficacy and Safety of Lonapegsomatropin in Adults With Growth Hormone Deficiency
A Trial to Investigate Long Term Effectiveness and Safety of Lonapegsomatropin in Adults With Growth Hormone Deficiency
- Signing of the trial specific informed consent.
- Completion of the treatment period and Visit 7 assessments of trial TCH-306, including
collection and upload of Visit 7 DXA scan.
- Fundoscopy at Visit 7 in trial TCH-306 without signs/symptoms of intracranial
hypertension or diabetic retinopathy stage 2 / moderate or above.
- Diabetes mellitus if any of the following are met:
1. Poorly controlled diabetes, defined as HbA1C higher than 7.5% according to
central laboratory at Visit 6 in trial TCH-306;
2. Use of diabetes mellitus drugs other than metformin and/or dipeptidyl peptidase-4
(DPP-4) inhibitors.
- Active malignant disease or history of malignancy. Exceptions are:
1. Resection of in situ carcinoma of the cervix uteri;
2. Complete eradication of squamous cell or basal cell carcinoma of the skin.
- Known history of hypersensitivity and/or idiosyncrasy to the investigational product
(somatropin or excipients).
- Female who is pregnant, plans to become pregnant, or is breastfeeding.
- Female participant of childbearing potential (i.e., fertile, following menarche and
until becoming post-menopausal unless permanently sterile) not willing throughout the
trial to use contraceptives as required by local law or practice.
- Male participant not willing throughout the trial to use contraceptives as required by
local law or practice.
- Any disease or condition that, in the judgement of the investigator, may make the
participant unlikely to comply with the requirements of the protocol or any condition
that presents undue risk from the investigational product or trial procedures.
Eligibility last updated 3/31/22. Questions regarding updates should be directed to the study team contact.
Methodology for Examining Elements in the Physical Environment Impacts on Fatigue and Resilient Performance
Examining Elements in the Physical Environment Impacts on Fatigue and Resilient Performance
- Practicing physicians, nurses and allied health staff that participate in surgery process.
- Physicians, Nurses and allied health staff that do not have time to participate in the study.
Eligibility last updated 3/8/22. Questions regarding updates should be directed to the study team contact.
The MCSA Sleep Study: Investigating Associations Between Sleep Characteristics, Cognitive Function, Alzheimer’s Disease and Vascular Pathology Biomarkers in Participants in the Mayo Clinic Study of Aging (MCSA)
Sleep Characteristics, Cognitive Function, Alzheimer’s Disease and Vascular Pathology Biomarkers in Cognitively Unimpaired Older Adults
- Age ≥ 60 years old at time of consent.
- Concurrent enrollment in the Mayo Clinic Study of Aging (MCSA, IRB 14-004401):
- Note: Participants may be but are not required to be concurrently enrolled in Brain Amyloid Imaging with Pittsburgh Compound B in Normal Aging, Mild Cognitive Impairment and Dementia (PiB, IRB 08-005553).
- Normal or mildly impaired cognition with CDR ≤ 1.0.
- History of dementia or major neurological condition (i.e., non-lacunar stroke, TBI, epilepsy, tumor, CNS infection, demyelinating disease, neurodegenerative disease), severe autonomic failure (pure autonomic failure or autonomic neuropathy), major psychiatric disease (i.e., alcohol/drug abuse and schizophrenia),
- Current treatment of OSA. Diagnosed but untreated OSA is acceptable.
- Use of short-acting nitrates within 3 hours of the sleep study.
- Use of selective α1-adrenergic receptor antagonists, for example, tamsulosin (Flomax®), doxazosin (Cardura®), prazosin (Minipress®), and terazosin (Hytrin®) and nonselective α1 and α2 blockers (pentholamine and phenoxybenzamine).
- Finger deformity that precludes adequate sensor application.
- Placement of a permanent pacemaker.
- Persistent atrial fibrillation or other sustained non-sinus cardiac arrhythmias.
- Severe peripheral vascular disease (e.g., status post stent or by-pass surgery in one of the limbs, faint/absent pulses).
- Status post bilateral cervical or thoracic sympathectomy.
- Acute lung or heart disease (e.g., decompensated COPD or heart failure).
Eligibility last updated 9/21/22. Questions regarding updates should be directed to the study team contact.
SGNTUC-029 - An Open-label Randomized Phase 3 Study of Tucatinib in Combination With Trastuzumab and mFOLFOX6 Versus mFOLFOX6 Given With or Without Either Cetuximab or Bevacizumab as First-line Treatment for Subjects With HER2+ Metastatic Colorectal Cancer (MOUNTAINEER-03)
Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer
- Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum
which is metastatic and/or unresectable
- Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE)
tumor tissue blocks (or freshly sectioned slides) obtained prior to treatment
initiation to a central laboratory
- If archival tissue is not available, a newly-obtained baseline biopsy of an
accessible tumor lesion is required within 35 days prior to start of study
treatment
- HER2+ disease as determined by a tissue based assay performed at a central laboratory.
- Participant has rat sarcoma viral oncogene homolog wild-type (RAS WT) disease as
determined by local or central testing
- Radiographically measurable disease per RECIST v1.1 with:
- At least one site of disease that is measurable and that has not been previously
irradiated, or
- If the participant has had previous radiation to the target lesion(s), there must
be evidence of progression since the radiation
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- CNS Inclusion
•based on contrast brain magnetic resonance imaging, participants may
have any of the following:
- No evidence of brain metastases
- Previously treated brain metastases which are asymptomatic
- Prior systemic anticancer therapy for colorectal cancer (CRC) in the metastatic
setting
- May have received chemotherapy for CRC in the adjuvant setting if it was
completed >6 months prior to enrollment
- Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting
of stereotactic radiosurgery)
- Previous treatment with anti-HER2 therapy
- Ongoing Grade 3 or higher neuropathy
- GI perforation within 12 months of enrollment
A Phase 1 Study in Patients with Clinically Node-Positive Breast Cancer to Assess the Safety, Ultrasound Conspicuity, and Migration of an Ultrasound Twinkling Marker Observed for Sonographic Targeting (UTMost Trial) (UTMost)
Assessment of the Safety, Ultrasound Conspicuity, and Migration of Twinkling Markers in Patients With Locally Advanced Breast Cancer Undergoing Neoadjuvant Systemic Therapy and Surgery, UTMOST Trial
- Patient 18 years or older with breast cancer and biopsy-proven malignant involvement of an axillary lymph node.
- Surgical management will be determined by Dr. Mara Piltin, who will decide if preoperative I-125 seed localization of the positive node is necessary or if she will retrieve the positive node with intraoperative ultrasound guidance. During surgery, the targeted node, its associated biopsy markers, I-125 seed if placed, and twinkling marker will be resected. The position of the marker in the lymph node or proximity to the node will be noted from the surgical and pathology documentation.
- Surgery will be performed by Dr. Mara Piltin.
- Patients must be able to understand the study procedures and comply with them for the entire length of the study.
- No contraception is necessary or required.
- Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Inability or unwillingness of individual or legal guardian/representative to give written informed consent.
- Current or past participation within a specified timeframe in another clinical trial, as warranted by the administration of this intervention.
Harnessing the Power of Technology to Transform Delirium Severity Measurement in the ICU
Power of Technology to Transform Delirium Severity Measurement in the ICU
Aim 1-3 Patient Participants
- Age ≥ 50 years old;
- Estimated length of stay ≥ 24 hours in ICU; and
- Are not admitted for acute alcohol intoxication, drug (prescribed or illicit) overdose or withdrawal.
Aim 3 Nurse Clinician Participants
- Age ≥ 18 years old;
- Employed by Mayo Clinic;
- Assigned to care for study patient for > 4 hours.
Aim 3 Care Partner Participants
- Age ≥ 18 years old;
- Proxy decision maker for patient participant;
- Willing to complete survey (verbal consent).
Aim 1-3 Patient Participants
- Admitted for acute alcohol intoxication, drug (prescribed or illicit) overdose or withdrawal;
- Admitted for acute neuronal injury;
- Unable to communicate with research team due to sensory deficits (aphasic, blind, deaf); or
- Language (does not speak English).
Aim 3 Nurse Clinician Participants
- Not assigned to study patient.
Aim 3 Care Partner Participants
- Did not visit patient in ICU during study period;
- Already listed above in previous protocol version, was not copied/mentioned here.
Eligibility last updated 12/1/22. Questions regarding updates should be directed to the study team contact.
A Multicenter, Randomized, Double-blind, Placebo Controlled, Phase 2b/3 Study to Evaluate the Efficacy and Safety of Saroglitazar Magnesium in Subjects With Primary Biliary Cholangitis (EPICS-III)
Saroglitazar Magnesium for Treatment of Primary Biliary Cholangitis
1. Males or females, between 18 and 75 years of age, both inclusive at screening.
2. Subjects on Ursodeoxycholic acid (UDCA) for at least 12 months at a therapeutic dose
(at least 13 mg/kg per day) and a stable dose for 6 months prior to Screening Visit
and having ALP ≥ 1.67 x ULN.
OR Subjects who are unable to tolerate UDCA and did not receive UDCA for at least 3
months prior to the date of screening and having ALP ≥ 1.67 x ULN.
3. History of confirmed PBC diagnosis, based on American Association for the Study of
Liver Disease [AASLD] and European Association for Study of the Liver [EASL] Practice
Guidelines, as demonstrated by the presence of at least ≥ 2 of the following 3
diagnostic factors:
1. History of elevated ALP levels for at least 6 months prior to screening
2. The subjects should have positive anti-mitochondrial antibodies (AMA) titer OR if
AMA is negative or in low titer (< 1:80), then the subjects should have PBC
specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the
major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex])
3. Liver biopsy consistent with PBC
4. ALP ≥ 1.67 x ULN at both Visits 1 and 2 and with < 30% variance between the levels
from Visit 1 to Visit 2
5. Total bilirubin < 2 x ULN at screening (Visit 1)
6. Must provide written informed consent and agree to comply with the trial protocol
1. Consumption of 2 standard alcohol drinks per day if male and 1 standard alcohol drink
per day if female for at least 3 consecutive months (12 consecutive weeks) within 5
year before screening (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce
of spirits/hard liquor).
2. History or presence of other concomitant liver diseases at screening:
1. Chronic hepatitis B or C virus (HBV, HCV) infection. (Note: However, If the
subject has been treated for the HCV infection and has been cured for a duration
of more than 2 years from screening, such subjects can be enrolled in the study)
2. Primary sclerosing cholangitis (PSC).
3. Alcoholic liver disease.
4. Autoimmune hepatitis (AIH) indicative of PBC with overlap syndrome.
Note: The Paris criteria are commonly used to define the presence of PBC with
features of AIH and have been endorsed by EASL and AASLD. According to these
criteria, a diagnosis can be made in a patient with PBC as follows:
At least two of the following:
I. ALP > 2 x ULN or GGT > 5 x ULN. II. AMA > 1:40. III. Florid bile duct lesion
on histology. AND
At least two of the following three features:
I. ALT > 5 x ULN. II. Immunoglobulin G serum levels > 2 x ULN or smooth muscle
autoantibody positive.
III. Moderate to severe interface hepatitis on histology.
5. Hemochromatosis.
6. Non-alcoholic steatohepatitis (NASH) on historical biopsy.
3. Cirrhosis with complications, including history or presence of: spontaneous bacterial
peritonitis, hepatocellular carcinoma, encephalopathy, known large esophageal varices
or history of variceal bleeding and active or history of hepatorenal syndrome at
screening.
4. Clinically silent compensated cirrhosis (at screening), defined as (a) nodular liver
contour by abdominal imaging with at least one sign of liver dysfunction (> ULN INR or
< LLN serum albumin); or (b) prolonged INR (> ULN) and diminished albumin (< LLN); or
(c) platelet count <140x109/L with INR > ULN or serum albumin < LLN.
5. Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease)
or which may diminish life expectancy to < 2 years, including known cancers.
6. Use of thiazolidinediones or fibrates (within 12 weeks prior to screening).
7. Use of obeticholic acid (OCA), azathioprine, cyclosporine, methotrexate,
mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (Note:
Prednisone dose should not be more than 10 mg per day); potentially hepatotoxic drugs
(including ?-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin) (within
12 weeks prior to screening).
8. Use of drugs that are known CYP2C8 inhibitors/substrate within 4 weeks prior to
screening (refer to Appendix 7 for List of Known CYP2C8 Inhibitors/Substrate).
9. History of bowel surgery (gastrointestinal [bariatric] surgery in the preceding 1 year
or undergoing evaluation for gastrointestinal surgery (bariatric surgery for obesity,
extensive small-bowel resection) or orthotopic liver transplant (OLT) or listed for
OLT.
10. Type 1 diabetes mellitus.
11. Unstable cardiovascular disease, including:
1. Unstable angina, (i.e., new or worsening symptoms of coronary heart disease in
the 12 weeks before screening and throughout the Screening Period), acute
coronary syndrome in the 24 weeks before screening and throughout the Screening
Period, acute myocardial infarction in the 12 weeks before screening and
throughout the Screening Period or heart failure of New York Heart Association
class (III
•IV) or worsening congestive heart failure, or coronary artery
intervention, in the 24 weeks before screening and throughout the Screening
Period.
2. History/current unstable cardiac dysrhythmias.
3. Uncontrolled hypertension at screening.
4. Stroke or transient ischemic attack in the 24 weeks before screening.
12. History of intracranial hemorrhage, arteriovenous malformation, bleeding disorder,
coagulation disorders, or screening blood tests that, in the opinion of the
Investigator, indicate altered coagulability (e.g., PT, INR, aPTT) at screening.
13. An uncontrolled thyroid disorder
1. Uncontrolled hyperthyroidism: defined as any history of hyperthyroidism that has
either not been treated with either radioactive iodine and/or surgery or that has
been treated with radioactive iodine and/or surgery, but has required ongoing
continuous or intermittent use of thyroid hormone synthesis inhibitors (i.e.,
methimazole or propylthiouracil) in the 24 weeks before screening.
2. Uncontrolled hypothyroidism: defined as initiation of thyroid hormone replacement
therapy or dose adjustment of replacement therapy in the 12 weeks before
screening.
14. History of myopathies or evidence of active muscle disease demonstrated by CPK ≥ 5 x
ULN at screening.
15. Subjects whose ALT, AST, or ALP exceeds by more than 50% on Visit 2 reading compared
to Visit 1. Note: If the ALT, AST, or ALP values on Visit 2 exceed by more than 50%
from Visit 1, then a third value will be measured (within 1- 2 weeks) to assess for
the trend. If the third value shows continued increase ≥ 10%, then subject is
considered ineligible for randomization.
16. Any of the following laboratory values at screening:
1. Platelets < 100 × 109/L
2. Albumin < 3.2 g/dL
3. eGFR < 60 mL/min/1.73 m2
4. ALP > 10 x ULN
5. ALT or AST > 250 U/L
17. Participation in another interventional clinical study and receipt of any other
investigational medication (within 12 weeks prior to randomization up to end of
study).
18. History of malignancy in the past 5 years and/or active neoplasm with the exception of
resolved superficial non-melanoma skin cancer.
19. Contraindications to Saroglitazar Magnesium or has any conditions affecting the
ability to evaluate the effects of Saroglitazar Magnesium.
20. Known allergy, sensitivity, or intolerance to the study drug, comparator, or
formulation ingredients.
21. Pregnancy-related exclusions, including:
1. Pregnant/lactating female (including positive pregnancy test at screening).
2. Fertile women and men, UNLESS using effective contraceptive methods (such as an
intra-uterine device or other mechanical contraception method with condom or
diaphragm and spermicide) throughout the study. For male subjects, contraception
measures (condom and spermicide) must be taken during the study, either by the
male participant or his female partner. (Note: Enrolled females otherwise must be
surgically sterilized for at least 24 weeks before screening or postmenopausal,
defined as 52 weeks with no menses without an alternative medical cause or
following sexual abstinence.)
22. History or other evidence of severe illness or any other conditions that would make
the subject, in the opinion of the Investigator, unsuitable for the study (such as
poorly controlled psychiatric disease, HIV, coronary artery disease, or active
gastrointestinal conditions that might interfere with drug absorption).
CASCADE-LUNG: Cancer Screening Assay Using DELFI; A Clinical Validation Study in Lung (DELFI-L201)
CASCADE-LUNG: Cancer Screening Assay Using DELFI; A Clinical Validation Study in Lung (DELFI-L201)
- All subjects
1. Ability to understand and provide written informed consent
2. Age ≥ 50 years
3. Current or former smoker
4. ≥ 20 pack-years (pack years = number of packs per day × number of years smoked)
5. An initial or annual follow-up lung cancer screening chest CT planned/scheduled
within 30 days after enrollment (i.e., enrollment chest CT scan)
- All subjects
1. Evidence of any diagnosed cancer (including prior lung cancer) other than
non-melanoma skin cancer or carcinoma in situ within 2 years prior to enrollment
2. Prior systemic therapy, definitive therapy, radiation, or surgical resection for
any cancer diagnosis within 2 years prior to enrollment (with the exception of
surgery for nonmelanoma skin cancer and biopsies)
3. Any history of hematologic malignancy or myelodysplasia within 2 years prior to
enrollment
4. Any history of organ tissue transplantation
5. Any history of blood product transfusion within 120 days prior to enrollment
6. Current pregnancy
7. Any condition that in the opinion of the Investigator should preclude the
participant's participation in the study
8. Past or current participation in any clinical study sponsored by Delfi
Diagnostics or any history of a LDT (Laboratory Developed Test) for early
detection of lung cancer by Delfi Diagnostics
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 4/10/23. Questions regarding updates should be directed to the study team contact.
A Pilot Study to Investigate Non-Invasive Positive Pressure Ventilation on Oxygen Saturations without Supplemental Oxygen at Altitude
Non-Invasive Positive Pressure Ventilation on Oxygen Saturations without Supplemental Oxygen at Altitude
- Healthy male or female participants.
- Between the ages of 18 and 89.
- Must have had experience as a pilot or passenger in an unpressurized general aviation aircraft at altitudes above 8,000 feet and have not experienced any serious adverse effects from this experience (such as serious vertigo, loss of consciousness, any cardiac or respiratory dysfunction, or any other illness requiring medical treatment).
- Participants need to be able to complete cognitive tests.
- Must be fluent in English.
- Patients < 18 years of age or > 89 years of age.
- Pregnant women.
- Unable to read and speak English.
- History of Cardiac disease, Pulmonary disease, Cerebrovascular disease, Neurological disease, Vertigo, or Syncope.
- Any documented incidences of Serious Adverse effects from General Aviation.
Patient Reported Outcomes After Hepatic Artery Infusion Pump Placement
Patient Outcomes after Hepatic Artery Infusion Pump Placement
- Patients who receive a Hepatic Artery Infusion Pump at Mayo Clinic Rochester for localized unresectable liver metastases from colorectal cancer.
- Age ≥ 18 years old.
- Written consent.
- Age < 18 years old.
- Absence of written consent.
- Systemic disease.
- Pregnancy.
A Pivotal Study to Evaluate the Safety and Effectiveness of Exablate Model 4000 Using Microbubble Resonators to Temporarily Mediate Blood-Brain Barrier Disruption (BBBD) for Liquid Biopsy in Subjects with Glioblastoma Brain Tumors
Blood-Brain Barrier Disruption (BBBD) for Liquid Biopsy in Subjects With GlioBlastoma Brain Tumors
- Male or female.
- Between > 18-80 years of age.
- Able and willing to give informed consent
- Subjects with a suspected glioblastoma tumor on pre-operative brain imaging scans.
- Subjects that are scheduled, or will be scheduled within 4 weeks, for surgical resection or biopsy per standard clinical tumor care.
- Karnofsky Performance Score > 70.
- Able to communicate sensations during the Exablate BBBD procedure.
- Tumor originating from the deep midline, thalamus, midbrain, cerebellum or brainstem.
- Multifocal tumors.
- MRI or clinical findings of:
- Active or chronic infection(s) or inflammatory processes;
- Acute or chronic hemorrhages, specifically any lobar microbleeds, and no siderosis, amyloid angiopathy, or macro-hemorrhages;
- Intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis.
- MR non-compatible metallic implants in the skull or the brain or the presence of unknown MR unsafe devices.
- Significant cardiac disease or unstable hemodynamic status:
- Documented myocardial infarction within six months of enrollment;
- Unstable angina on medication;
- Unstable or worsening congestive heart failure;
- Left ventricular ejection fraction below the lower limit of normal;
- History of a hemodynamically unstable cardiac arrhythmia;
- Cardiac pacemaker;
- History of hypersensitivity to Perflutren lipid microsphere or its components; e.g., polyethylene glycol.
- Uncontrolled hypertension (systolic > 180 and diastolic BP > 120 on medication).
- Unable to discontinue use of anti-coagulant/antiplatelet therapy as per local standard.
- History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage or evidence of increased risk of bleeding.
- Abnormal coagulation profile (Platelets < 80,000), PT (> 14) or PTT (> 36), and INR > 1.3.
- Known cerebral or systemic vasculopathy.
- Significant depression and at potential risk of suicide.
- Known sensitivity/allergy to gadolinium or DEFINITY®.
- Active seizures despite medication treatment (defined as > 1 seizure per week) which could be worsened by disruption of the blood brain barrier.
- Active drug or alcohol disorder which have a higher risk for seizures, infection and/or poor executive functioning.
- Positive HIV status, which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis.
- Potential blood-borne infections which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess.
- Any contraindications to MRI scanning, including:
- Large subjects not fitting comfortably into the scanner;
- Difficulty lying supine and still for up to 3 hours in the MRI unit or claustrophobia.
- Impaired renal function with estimated glomerular filtration rate < 30 mL/min/1.73m^2.
- Severe Respiratory Illness: chronic pulmonary disorders; e.g.,severe emphysema, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area, subjects with a history of severe drug allergies, asthma or hay fever, and multiple allergies where the benefit/risk of administering Definity® is considered unfavorable by the study physicians in relation to the product labeling for Definity®.
- Currently in a clinical trial involving an investigational product or non-approved use of a drug or device.
- Pregnancy or lactation.
Bipolar Disorder Measures in Clinical Care - Patient Preferences on Measures
Bipolar Disorder Measures in Clinical Care
- 18 years or older with a clinician diagnosis of bipolar disorder (any bipolar disorder type including bipolar I disorder, bipolar II disorder, cyclothymic disorder, and unspecified bipolar and related disorder).
- Ability to consent to participation in research.
- Patients (n=10) will be recruited from those currently receiving treatment in the included clinics in the Mayo Clinic (Collaborating Institution).
- Additionally, stakeholder partners at the Depression and Bipolar Support Alliance will publicize our research study and identify 10-15 individuals with bipolar disorder currently receiving treatment to participate.
- Among participants recruited from the Mayo Clinic, individuals who are not intending to return to care in that system.
- No exclusion criteria apply to participants recruited from the Depression and Bipolar Support Alliance.
A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Depemokimab in Adults with Hypereosinophilic Syndrome (HES)
A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Depemokimab in Adults With Hypereosinophilic Syndrome (HES)
- Participant must be ≥ 18 years of age, at the time of signing the informed consent.
- Participants who are ≥ 40 kg at Screening Visit 1.
- Participants who have a documented diagnosis of HES prior to Visit 2. HES diagnosis is based on:
- blood eosinophilia of > 1500 eosinophils/µL on at least 2 occasions at ≥ 1-month interval, without a discernible non-haematological secondary cause; and
- signs or symptoms of organ involvement and/or dysfunction that can be directly related to eosinophilia.
- Flare history: A history of 2 or more HES flares within the past 12 months prior to Visit 1. Historical HES flares are defined as documented HES-related worsening of clinical symptoms or blood eosinophil counts requiring an addition or escalation in OCS or cytotoxic/immunosuppressive therapy. At least one HES flare within the past 12 months must not be related to a decrease in HES therapy during the 4 weeks prior to the flare.
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
- Is a woman of non-childbearing potential (WONCBP); OR
- Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, from at least 14 days prior to the first dose of study intervention until at least 30 weeks after the last administered dose of study intervention. The Investigator should evaluate the potential for contraceptive method failure (e.g., non-compliance, recently initiated) in relationship to the first dose of study intervention;
- A WOCBP must have a negative highly sensitive serum pregnancy test at Screening Visit 1 and a negative highly sensitive urine pregnancy test within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention;
- Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies;
- The Investigator should evaluate the potential for contraceptive method failure (e.g., non-compliance, recently initiated in relationship to the first dose of study intervention;
- The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
- HES disease manifestations which in the opinion of the Investigator may put the participant at unacceptable risk from study participation or confound interpretation of efficacy or safety data. Specific consideration should be given to the participant’s ability to comply with protocol requirements, including the list of prohibited therapies; exclusion criteria no. 14
•16. - Participants with chronic or ongoing active infections requiring systemic treatment.
- Participants with a pre-existing parasitic infestation within 6 months prior to Visit 1.
- Participants with a known immunodeficiency (e.g., Human Immunodeficiency Virus [HIV]), other than that explained by the use of OCS or other therapy taken for HES.
- Participants with a history of or current lymphoma.
- Participants with current malignancy or previous history of cancer in remission for less than 5 years prior to Visit 1. Participants that had localized carcinoma (i.e., basal or squamous cell) of the skin which was resected for cure will not be excluded.
- Participants with a haematologic malignancy with hypereosinophilia in which HES is not the primary diagnosis; e.g., chronic myeloid leukaemia, myelodysplastic syndrome, chronic eosinophilic leukaemia-not otherwise specified.
- Cirrhosis or current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice.
- NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C) are acceptable if participant otherwise meets entry criteria.
- Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
- Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at Screening will be evaluated and current vasculitis must be excluded prior to randomization.
- Eosinophilia of unknown significance: Hypereosinophila with no clinical symptoms and/or proof of organ dysfunction.
- Clinical diagnosis of EGPA.
- Participants that, according to the Investigator's medical judgment, are likely to have active COVID-19 infection should be excluded.
- Participants with known COVID-19 positive contacts within the past 14 days must be excluded for at least 14 days following the exposure during which the participant must remain symptom-free.
- Participants who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory, cardiac or any other system abnormalities that are not associated with HES and are uncontrolled with standard treatment.
- Participants with an allergy/ intolerance to a monoclonal antibody or biologic, or any of the excipients of the investigational product.
- Monoclonal antibodies (mAbs) targeting IL-5/5R: Participants who have a previous documented failure with anti-IL-5/5R therapy.
- Participants who have received mAb within 30 days or 5 half-lives, whichever is longer, prior to Visit 1. If a participant has been treated with and responsive to biologics for HES, the participant should not stop the treatment for study eligibility purpose.
- Non-oral systemic corticosteroids: Participants who have received intravenous, intramuscular, or subcutaneous corticosteroids within 4-weeks prior to Visit 2.
- Participants who have received treatment with an investigational agent within 30 days or 5 drug half-lives whichever is longer, prior to Visit 1. The term “investigational” applies to any drug not approved for sale in the country in which it is being used or investigational formulations of marketed products.
- Participants who are currently participating in any other interventional clinical study.
- Note: Any COVID-19 vaccine approved by local government is permitted. Experimental COVID-19 vaccines are not permitted.
- Participants who test positive for the FIP1L1-PDGFRα fusion gene. Blood sampling is required for all participants at Screening (Visit 1) for this test unless the documented result is available.
- ECG Assessment: QTcF ≥ 450 msec or QTcF ≥ 480 msec for participants with Bundle Branch Block at Screening Visit 1.
- Participants who are not responsive to OCS based on clinical response or blood eosinophil counts in the opinion of the Investigator.
- A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
- Participants who are pregnant or breastfeeding.
- Participants must not be randomized if they plan to become pregnant during the time of study participation.
- Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations.