Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 7/18/23. Questions regarding updates should be directed to the study team contact.

Diagnosis of B-cell lymphoma, CLL or B-ALL as described below:  

• B-Cell Lymphoma:
  • Histologically documented lymphomas expected to express CD19;
  • Relapsed/refractory disease following at least 2 prior lines of multi-agent  immunochemotherapy.
• Chronic Lymphocytic Leukemia (CLL):
• Diagnosis of CLL per iwCLL guidelines;
  • Relapsed/refractory disease following at least two prior systemic treatment regimens.
• Precursor B-cell Acute Lymphocytic Leukemia (B-ALL):
  • Diagnosis of B-ALL by flow cytometry, bone marrow histology, and/or cytogenetics;
  • Relapsed/refractory disease after at least 2 cycles of standard multiagent induction  chemotherapy.
  • For subjects with Philadelphia-chromosome positive (Ph+) disease, failure or intolerance to a tyrosine kinase inhibitor therapy-containing regimen.

ALL SUBJECTS

• Capable of giving signed informed consent.
• Age ≥ 18 years old.
• Stated willingness to comply with study procedures and duration.
• Contraceptive use for women and men as defined in the protocol.

ALL SUBJECTS

• Females who are pregnant or breastfeeding.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 2.
• Body weight < 50 kg.
• Evidence of insufficient organ function.
• Receipt of therapy within 2 weeks prior to Day 1 or five half-lives, whichever is  shorter; or any investigational therapy within 28 days prior to Day 1.
• Currently receiving or likely to require systemic immunosuppressive therapy.
• Ongoing requirement for systemic GvHD therapy following prior allogeneic hematopoietic stem cell transplant (HSCT) or allogeneic CAR-T.
• Receipt of an allograft organ transplant.
• Known active central nervous system (CNS) involvement by malignancy.
• Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or  neurodegenerative disease.
• Clinically significant cardiovascular disease.
• Positive serologic test results for HIV infection.
• Positive serologic and polymerase chain reaction (PCR) test results for Hepatitis B  (HBV) infection.
• Positive serologic and PCR test results for Hepatitis C (HCV) infection.
• Live vaccine < 6 weeks prior to start of lympho-conditioning.
• Known allergy to albumin (human) or DMSO.

Eligibility last updated 1/7/22. Questions regarding updates should be directed to the study team contact.

• Over 18 years old.
• Fusion of the MCP joint at Mayo Clinic between January 01, 1990- December 31, 2020.

• Individuals under 18 years old.

Eligibility last updated 2/7/22. Questions regarding updates should be directed to the study team contact.

• A person with one of the identified genetic conditions OR a parent or guardian of a child or young adult previously diagnosed with the condition or otherwise at risk of the condition OR a spouse or primary relative of an individual currently experiencing or who has died as a result of a disease of interest;
  • The diseases of interest are:
    • Tay Sachs;
    • Spinal Muscular Atrophy;
    • Huntington’s;
    • Thalassemia;
    • Sickle Cell;
    • Phenylketonuria;
    • BRCA1 and 2;
    • Alzheimer’s;
    • Autism Spectrum  Disorder;
• Hereditary Deafness or Hearing Loss.
• ≥ 18 years of age.
• English speaker.

• Not affected or not affected by a disease of interest.
• No parental, spousal, or familial relationship to a person with a disease of interest..
• < 18 years of age.
• Not an English speaker.

Eligibility last updated 12/11/23. Questions regarding updates should be directed to the study team contact.

• Male and female subjects, 15
  •70 years of age.
• Previous diagnosis of ADPKD (based on Ravine et al. criteria).
• Class 1 A-E according to imaging classification.
• Estimated GFR > 45 mL/min/1.73 m^2 (CKD-EPI).
• Ability to provide written, informed consent.

• Class 2, according to imaging classification.
• A concomitant systemic disease affecting the kidney.
• Diabetes mellitus.
• Predicted urine protein excretion in > 1 g/24 hrs and/or Abnormal urinalysis.
• Use of antioxidants; i.e., vitamins, Nrf2 activators.
• Patients that are part of an interventional study.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/5/23. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 5/3/23. Questions regarding updates should be directed to the study team contact.

• Adult males and females, 18
  •65 years of age, inclusive, at screening; or be a male or female child age 12 and up whose weight >=50 kg.
• For children: be up to date on childhood vaccinations, specifically varicella vaccine (chicken pox) and Measles, Mumps & Rubella.
• Children's parent or legal guardian has provided written informed consent/Health Insurance Portability and Accountability Act authorization prior to any study-related procedures.
• Subject and parent/guardian are willing and able to comply with scheduled visits, study drug administration plan, study restrictions, and study procedures.
• For adults: Body mass index (BMI) ≤ 36.0 kg/m2 at screening.
• Confirmed genetic diagnosis of CPVT1 and supporting clinical phenotype, including residual ventricular ectopy (i.e. a complexity score >0) on their last exercise stress test on a stable medical regimen.
• Must have a CYP2C8 extensive or intermediate metabolizer genotype.
• Daily use of medicines and dietary supplements need to be approved by the PI and Sponsor, or a drug/supplement-dependent wash-out prior to inclusion.
• For male subjects:
  • is sterile or agrees to use an appropriate method of contraception;
  • including a condom with spermicide, from study drug administration on the first day of dosing until 5 half-lives plus 90 days (approximately 94 days) after the last dose of study drug administration. No restrictions are required for a vasectomized male subject provided the subject is at least 1-year post-bilateral vasectomy procedure prior to study drug administration on first day of the first dose. A male subject whose vasectomy procedure was performed less than 1 year prior to study drug administration on the first day of dosing must follow the same restrictions as a non-vasectomized male. Appropriate documentation of surgical procedure should be provided.
• For male subjects: agrees to not donate sperm from study drug administration on the first day of dosing until 5 half-lives plus 90 days (approximately 94 days) after the last dose of study drug.
• For female subjects of childbearing potential: uses one of the following highly effective birth control methods (from the first dose until 5 half-lives plus 90 days (approximately 94 days):
  • Prescribed hormonal oral contraceptives, vaginal ring, or transdermal patch;
  • Intrauterine device (IUD);
  • Intrauterine hormone-releasing system (IUS);
  • Depot/implantable hormone (e.g., Depo-Provera®, Implanon);
  • Bilateral tubal occlusion/ligation.
• Sexual abstinence:
  • Refraining from heterosexual intercourse during the entire period of risk associated with the study requirements;
  • If the participant decides to become sexually active during the study, then one of the highly effective birth control methods must be used.
• For female subjects of non childbearing potential; defined by at least 1 of the following criteria:
  • Postmenopausal defined as 12 months of spontaneous amenorrhea and follicle stimulating hormone (FSH) serum level > 40mIU/mL. Appropriated documentation of FSH levels is required;
  • Surgically sterile by hysterectomy and/or bilateral oophorectomy with appropriate documentation of surgical procedure;
  • Has a congenital condition resulting in no uterus.
• Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, study restrictions, and study procedures (exercise testing and PK sampling).
• Able to provide written informed consent or assent and understands the study procedures in the informed consent form (ICF) or assent form.

• Patient is mentally or legally incapacitated at the time of the screening visit or during the conduct of the study.
• History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose of study drug.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drug, related compounds, or inactive ingredients.
• Positive urine drug or alcohol results at screening.
• Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
• Patients with baseline ALT or AST levels three times above the upper limits of normal (ULN) (isolated elevations of total bilirubin < 2 X ULN with direct bilirubin below the ULN will be included).
• Patients with a history of documented epileptic seizures (not including febrile or Stokes-Adams events, i.e. cardiovascular syncope).
• Subject has a history of cancer (malignancy)
  • Exceptions: Subjects with adequately treated non-melanomatous carcinoma or carcinoma in situ of the cervix may participate in the trial, subjects with other malignancies who have been successfully treated > 10 years prior to the screening where in the judgment of the investigator has revealed no evidence of recurrence from the time of treatment through the time of the screening except those identified at the beginning of the exclusion criterion, or subjects who in the opinion of the investigator are highly unlikely to sustain a recurrence for the duration of the trial.
• Patients with uncontrolled diabetes defined as HbA1c > 7% or diabetic neuropathy.
• Estimated creatinine clearance < 40 mL/minute at screening.
• Patients with a clinically significant abnormality on their resting ECG other than hypertensive related, or heart failure (ejection fraction <30%) or other clinically significant structural heart disease on echocardiogram.
• Patients with a history of myocardial infarction in the last five years, or evidence of congestive heart failure.
• Pregnant and breastfeeding women.
• Unable to refrain from or anticipates the use of:
  • Any non-approved medicines and/or dietary supplements beginning 14 days prior to the first dose of study drug and throughout the study. Thyroid hormone replacement medication may be permitted if subject has been on same stable dose for the last 3 months prior to the first dose of study drug;
  • Any drugs known to be significant inducers or inhibitors of CYP2C8 enzymes for 28 days prior to the first dose of study drug and throughout the study. Any substrates of breast cancer resistance protein (BCRP).
• Is currently taking any drug which raises gastric pH, including proton pump inhibitors or H2 antagonists. Antacids may be used if taken at night.
• Donation of blood or significant blood loss within 56 days prior to the first dose of study drug.
• Plasma donation within 7 days prior to the first dose of study drug.
• Participation in clinical trials for other therapeutic investigational drugs simultaneously or within the 4 weeks prior to the first dose of study drug.
• Ongoing medical condition that is deemed by the Principal Investigator to interfere with the conduct or assessments of the study or safety of the subject.
• Is unable to take orally administered tablets.
• Have known allergy or intolerance to lactose, present in placebo tablets.
• Is an immediate family member of the sponsor or employee of the clinical site or may consent under duress.

• Patient must have documented T cell ALL and must be in first or later hematologic CR or CRi after a minimum of 2 blocks of intensive chemotherapy.
• Patients in hematologic CR or CRi must have persistent or recurrent MRD ≥ 10-4.
• Institution must have received central MRD status test results confirming persistent or recurrent MRD ≥ 10-4 by flow cytometry.
• Patient may have undergone a prior allogeneic stem cell transplant, but patient may not have Grafts Versus Host Disease (GVHD) that requires ongoing immunosuppressive therapy. Patient may receive prednisone if the dose is ≤ 10 mg per day.
• Patient must have an ECOG performance status 0-2.
• All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 registration to rule out pregnancy.
• Patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and continue to 3 months after the last dose of protocol treatment. Patients must also agree to abstain from donating sperm,beven if they have had a successful vasectomy, or donating eggs while on study treatment and for 3 months after the last dose of protocol treatment.
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
• Patient must have adequate organ and marrow function as defined below (these labs must be obtained ≤ 7 days prior to Step 1 registration).
• Absolute neutrophil count (ANC) ≥ 750/µL.
• Platelets ≥ 75,000/µL.
• Total or Direct bilirubin ≤ 2 mg/dL.
• AST(SGOT)/ALT(SGPT) ≤ 3.0 × institutional ULN.
• Creatinine ≤ 1.5 x institutional ULN or Creatinine Clearance > 30 ml/min.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with prior CNS involvement are eligible as long as they do not have active CNS involvement at time of Step 1 registration.
• 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.

• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria

• Previous TBI NDB enrollees from each TBIMS center who are 5 years post-injury.
• English speaking.
• Not currently incarcerated.
• Not experiencing severe psychosis (other co-morbid psychiatric disorders are acceptable).
• Participants will have completed the BTACT at least two times over the first 5 years post-TBI and are currently able to complete the BTACT. 
• Participants will have, at some point in the first 5 years after TBI, met the empirically-based definition of high suicide risk:
  • a score ≥ 1 on item 9 of previously collected PHQ-9 (“Thoughts you would be better off dead, or thoughts of hurting yourself in some way” on “Several days,” “More than half the days,” or “Nearly every day” in the past 2 weeks; OR
  • past-year suicide attempt; OR
  • past-year suicide  hospitalizations).

• < 18 years of age. 

Eligibility last updated 9/20/22. Questions regarding updates should be directed to the study team contact.

• History of IBD defined by a physician global assessment (PGA) of quiescent, mild, moderate, or severe disease.
• 18 years old or older.
• Access to internet/device such as smart phone, tablet or computer.
• No corticosteroids in the previous 3 months.
• Patient reports stress as a trigger to their GI symptoms.
• No elicit substance use (including medical marijuana).

• < 18 Years of age. 

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.

Inclusion Criteria:

• Patients that come for facial plastic/reconstructive surgery involving facial fat injection or other facial reconstruction surgery.

Exclusion Criteria:

• Patients treated with immunotherapy.
• Patients treated with chemotherapy/radiation therapy.
• Smokers.
• Patients with immuno-suppressed or compromised disease.
• Patients with diabetes.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 6/7/23. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 5/8/23. Questions regarding updates should be directed to the study team contact.

• Postpartum women over the age of 18 years old currently weaning.
• Able to provide informed consent.
• Women willing to provide a survey and breast fluid specimens obtained by pumping and by hand expression.

• Men.
• Women under the age of 18 years.
• Women with a history of cancer (other than non-melanoma skin cancer).
• Women with history of breast surgery.
• Women taking medication to reduce milk production.
• Unable to provide informed consent.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/22/22 Questions regarding updates should be directed to the study team contact.

• Males or females aged 18 to 65 years (inclusive).
• Clinical diagnosis of sAH based on all the following:
  • History of excess alcohol (> 60 g/day [male] or > 40 g/day [female]) use for ≥6 months, with < 60 days of abstinence prior to the onset of jaundice;
  • Serum total bilirubin > 3.0 mg/dL;
  • AST ≥ 50 U/L;
  • AST/ALT ratio ≥ 1.5;
  • Maddrey's Discriminant Factor (MDF) ≥ 32 and ≤ 60;
  • MELD-Na score 18 to 25 (inclusive).
• Onset of jaundice within 8 weeks from the time of admission to the hospital.
• Up to and not more than 7 days since admission to the hospital.
• Female subjects must be postmenopausal, surgically sterile, or, if premenopausal (and not surgically sterile), be prepared to use ≥1 highly effective method of contraception during the study and for 90 days after the last dose of investigational product as follows:
  • Surgical sterilization (bilateral tubal occlusion, etc.);
  • Placement of an intrauterine device (IUD) or intrauterine system (e.g.,  intrauterine hormone-releasing system [IUS]);
  • Combined (estrogen and progesterone containing) hormonal contraceptive associated with inhibition of ovulation:
    • Oral;
    • Intravaginal;
    • Transdermal.
  • Progesterone-only hormonal contraception associated with inhibition of ovulation:
    • Oral;
    • Injectable;
    • Implantable;
    • Sexual abstinence, if in line with the preferred and usual lifestyle of the subject (where true abstinence is defined as refraining from heterosexual contact intercourse during the entire period of risk associated with study treatments).
• Male subjects who are sexually active with female partners of childbearing potential must agree to use a condom with spermicide and to use one other approved method of highly effective contraception from the time of investigational product administration for at least 90 days after the dose of investigational product as listed in Inclusion Criteria #5.
• Male subjects must refrain from sperm donation from Screening through at least 90 days following the last dose of investigational product.
• Must provide written informed consent and agree to comply with the study protocol. In subjects with hepatic encephalopathy which may impair decision-making, consent will be obtained per hospital procedures (e.g., by Legally Authorized Representative).
• Subjects must agree to participate in an alcohol use disorder program during the study period, as recommended by the local institution's addiction medicine specialists, including post-hospitalization.

• Subjects taking systemic corticosteroids or products containing obeticholic acid in the 30 days prior to Screening, up to and including randomization.
• Pregnancy, planned pregnancy, potential for pregnancy (e.g., unwillingness to use effective birth control during the study), or current or planned breast feeding.
• Cessation of alcohol consumption for ≥2 months before Day 1.
• AST or ALT > 400 U/L.
• MDF < 32 or > 60 at Screening.
• MELD-Na score < 18 or > 25 at Screening (confirmed by repeat labs within 48 hours).
• Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen [HBsAg] positive), chronic hepatitis C virus (HCV) RNA positive, acetaminophen hepatotoxicity, biliary obstruction, and autoimmune liver disease.
• Current or previous history of hepatocellular carcinoma (HCC).
• History of liver transplantation or currently listed for liver transplant.
• Untreated sepsis (e.g., has not initiated appropriate medical treatment for infection and/or septic shock).
• Known positivity for human immunodeficiency virus infection.
• Uncontrolled gastrointestinal (GI) bleeding or controlled GI bleeding within 7 days of Screening that was associated with shock or required transfusion of more than 3 units of blood.
• Kidney injury defined as a serum creatinine >133 µmol/L (> 1.5 mg/dL) confirmed by repeat testing within 48 hours or the requirement for renal replacement therapy.
• Portal vein thrombosis.
• Acute pancreatitis or acute gallbladder disease (e.g., cholecystitis).
• Severe associated disease (e.g., cardiac failure, acute myocardial infarction, severe cardiac arrhythmias, severe pulmonary disease, neurologic disease).
• Malignancy within the 2 years prior to Screening, with the exception of specific cancers that have been cured by surgical resection (e.g., basal cell skin cancer).
• Subjects under evaluation for possible malignancy are not eligible.
• Positive urine drug screen (amphetamines, barbiturates, benzodiazepines, cocaine, and opiates) except tetrahydrocannabinol or in the setting of documented prescription medications (e.g., opiates, benzodiazepines, amphetamines, barbiturates), including medications prescribed as part of in-patient management. Subjects being treated for alcohol withdrawal may be exempt, if verified by the Medical Monitor..
• Participated in a clinical research study and received any active investigational product being evaluated for the treatment of sAH within 3 months before Day 1.
• Participation in a study of another investigational medicine or device within 30 days before Screening.
• Any other condition or clinical laboratory result that, in the opinion of the Investigator, might confound the results, or would impede compliance or hinder completion of the study.
• Received a positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test result within 4 weeks of Screening or a SARS-CoV-2 vaccination within 2 weeks of Screening.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/24/23. Questions regarding updates should be directed to the study team contact.

• Male or female.
• Age ≥ 18 years old.
• Biochemically and/or genetically confirmed or confirmed primary mitochondrial myopathy based on published diagnostic criteria.
• Biochemically confirmed mitochondrial disorder would mean that the patient meets clinical criteria and has either biopsy or biochemical testing that supports the diagnosis. Confirmed mitochondrial disorder means that the patient meets published clinical criteria for the diagnosis and has also had confirmatory genetic testing for the disorder type.
• Agreed to avoid vitamin supplementation or nutritional products with vitamin B3 forms 14 days prior to the enrollment and during the study in order to not exceed 200 mg/day of vitamin B3 derivatives intake.
• Female of childbearing potential agreed to use effective contraception throughout the study.
• Written, informed consent to participate in the study.

• Individuals < 18 years old.
• Unwilling to comply with the follow-up schedule.
• Inability or refusal to give informed consent by the patient or a legally authorized representative.
• Known pregnancy or breastfeeding.
• Concurrent participation in another investigational drug study or within washout period of treatment.
• Presence of other medical symptoms or condition, which may interfere with interpretation of outcome measures as determined by the study PI.

Clinical / Laboratory

• Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min.
• Patients in permanent Renal Replacement Therapy.
• Serum alkaline phosphatase 50% above normal limit.
• Serum aspartate transaminase 50% above normal limit.
• Serum Thyroxine (T4) 50% above or below normal limit.
• Serum Thyroid Stimulating Hormone (TSH) 50% above or below normal limit.
• Severe anemia with Hb < 7g/dL.
• Severe leukocytosis with WBC > 15,000/mm^3.

Eligibility last updated 4/18/22. Questions regarding updates should be directed to the study team contact.

• Adolescent patients age 13-17 at the time of clinical evaluation.
• Documented COVID infection (positive PCR, rapid COVID test, or positive antibody testing following suggestive clinical syndrome or known exposure).
• Post-COVID symptoms primarily characterized by fatigue, autonomic dysfunction, or pain persisting > 12 weeks from initial diagnosis.
• Access to both patient portal and Zoom, for virtual coaching sessions.
• English speaking.

• Severe anxiety or depression (defined as psychiatric hospitalization in the past 12 months, current or recent suicidal ideation or plan, or anxiety/depression primarily causing missed school or activities, or clinician assessment).
• Prior medical complexity, as defined by clinician.
• Severe COVID illness, with evidence of end-organ damage or requiring hospitalization.
• Acute COVID-19 infection.
• No prior positive SARS-CoV2 testing.
• Age ≥ 18 years at time of initial clinical evaluation.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 6/9/23. Questions regarding updates should be directed to the study team contact.

• Trauma activation level yellow or red.

• Prisoners, greater than 12 hours from time of injury, current injuries related to suicide attempt.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/10/22. Questions regarding updates should be directed to the study team contact.

• Be able to provide informed consent and be willing to sign an Informed Consent Form (ICF).
• Adults, aged 18-80 years at the time of signing the ICF (minimum representation target of at least 30% per gender).
• History of primary, idiopathic, or secondary, chronic intestinal pseudo-obstruction (CIPO) as confirmed by a physician.
• Capable of oral nutrition (including partial oral nutrition).
• Currently resides in the US.
• Ability to read, speak, and understand English (US English) fluently.
• Be willing and able to participate in up to two interviews lasting approximately 90--minutes in total via a videoconference platform (e.g., MS Teams):
  • Participants may be asked to participate in an additional interview lasting approximately 30 minutes.
• Willing to have the interview audio recorded (Note: no video-recording will be made).
• Have reliable access to high-speed internet.

• History of any serious psychiatric disorder or other condition (e.g., Alzheimer’s disease, dementia, schizophrenia, or other disorders that impair memory or cognitive function) that could interfere with participant providing informed consent or participating in an interview to discuss about their health with particular reference to their health-related quality of life (HRQoL) and CIPO-related symptoms.
• Active malignancy [a malignant cancer (with the exception of treated intraepithelial neoplasia, basal cell or squamous cell carcinoma of the skin), diagnosed within the previous six months, recurrent, invasive/regionally advanced or metastatic cancer for which treatment had been administered within six months, and any form of malignant cancer that is not in complete remission and/or that requires active treatment, including surgery or palliation].
• Recent abdominal or pelvic surgery (i.e., surgery, including laparoscopic surgery) performed within 6 months prior to screening).
• Any type of late-stage disease treated with palliative care (i.e., end-of-life care) that would prevent completion of the study or interfere with analysis of study results, at the discretion of the investigator.
• Physician-confirmed acute infection (i.e., currently on antibiotic therapy at the time of signing the ICF) involving the GI tract (e.g., viral or bacterial gastroenteritis, acute viral hepatitis) or the abdominal cavity (e.g., cystitis, fungal peritonitis).
• Subjects with conditions characterized by actual (unresolved) mechanical intestinal obstruction (e.g., volvulus, adhesions, hernias, Crohn’s disease, diverticulitis, actual presence of fecalith, or fecal impaction).
• Patients who are on Total Parenteral Nutrition (TPN) (100% reliant on parenteral nutrition) at screening.
• Use of opioids [such as narcotics (including, but not limited to, heroin, morphine and analogue molecules/derivates, oxycodone, hydrocodone, hydromorphone, buprenorphine, fentanyl, codeine), μ agonist, δ-opioid receptor antagonist (e.g., eluxadoline), loperamide] within 2 weeks prior to screening and during study participation.
• Pregnant women.
• Failure to be eligible to participate in the study for any reason or circumstance that, according to the Investigator's judgment, would prevent completion of the study or interfere with analysis of study results (e.g., recent history of drug abuse).
• Unwilling or unable to comply with the study procedures.
• Presence of other clinically significant disease(s) that in the Investigator’s opinion could adversely affect the quality of life of the patient or could impair the assessment of the study results.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/20/22. Questions regarding updates should be directed to the study team contact.

• Scheduled for two-stage exchange arthroplasty due to hip or knee periprosthetic joint infection (PJI).
• Signed informed consent.
• 22 to 84 years of age (inclusive).
• Medical clearance for surgery.
• Preoperative diagnosis of PJI of the hip or knee per the International Consensus.
• Meeting of Musculoskeletal Infection (ICMMI) 2018 definition of Periprosthetic Hip and Knee Infection.

• Patients with 2 or more prior exchange arthroplasties (septic or aseptic) of the infected joint. Exchange of modular components only is not considered an exchange arthroplasty.
• Patients with 2 or more prior failed spacers for PJI.
• Patients for whom a Stage 2 procedure within one year is contraindicated.
• Patients with bacteremia or positive bacterial blood culture in the last 30 days.
• Patients with concurrent PJI of more than one joint.
• Patients with ongoing active infection of an IV site.
• Patients who require long-term anticoagulation or antiplatelet therapy, and for whom bridging or withholding therapy is not recommended based on the individual’s clinical condition.
• Patients with advanced renal insufficiency (i.e., CKD Stage 4 or 5 or patients with an estimated glomerular filtration rate (eGFR) 10 mg/day or equivalent).
• Patients who are immunodeficient (e.g., splenectomy, sickle cell anemia, Stage 3 HIV infection, primary immunodeficiency disease), except patients who are immunodeficient due to immunosuppressive therapy.
• Patients who have an allergy to vancomycin hydrochloride or tobramycin sulfate (Note: prior history of red man syndrome is not considered an allergy);
• Patients who have an allergy to titanium, titanium alloys, polymethylmethacrylate, polyethylene, or polyurethane.
• Patients who are pregnant or planning to become pregnant in the next 12 months.
• Patients with a fungal PJI as determined by fluid and/or tissue culture.
• Patients who have a skeletal defect of greater than 150 mm in length in the tibia or femur of the infected joint.
• Patients who have a planned surgical procedure within 6 months of enrollment that can impact the conduct of the study.
• Patients who are breastfeeding.
• Patients who are incarcerated or are facing impending incarceration.
• Patients who have been in treatment or referred to treatment for substance abuse within the past year.
• Patients who have any medical condition including schizophrenia or another psychiatric disorder with hallucinations and/or delusions that would interfere with the interpretation of the study results, the conduct of the study, or study participation would not be in the best interest of the patient in the opinion of the Study Site PI.
• Patients who will participate in another clinical study of an investigational drug or investigational device or have participated in another clinical study of an investigational drug or investigational device within the past 30 days that would interfere with the interpretation of the study results or the conduct of the study.
• Patients who are judged by the Study Site PI to be unsuitable for the study.
• Patients receiving immunosuppressive therapy for bone marrow or another transplant.
• Patients currently or previously enrolled in this study or the APEX study (JPS-0301).
• Patients who receive therapy including any of the following drugs, which will not be withheld for a period beginning at least one dosing cycle (minimum 7 days) prior to planned surgery and ending at least 14 days following planned surgery: Adalimumab (Humira) Tocilizumab (Actemra) Etenercept (Enbrel) Anakinra (Kineret) Golimumab (Simponi) Secukinimab (Cosentyx) Infliximab (Remicade) Ustekinumab (Stelara) Abatacept (Orencia) Rituximab (Rituxan) Certolizumab (Cimzia) Tofacitinib (Xeljanz) Belimumab (Benlysta).

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/21/23. Questions regarding updates should be directed to the study team contact.

• All race/ethnicity categories, English speaking, men and women.
• Age ≥ 21 years.
• Current severe/massive/torrential tricuspid regurgitation (TR), considered symptomatic from TR.
• Goal Age/Sex/Race Distribution: ≥ 20% non-white, 40% women/men, 40% < 65/ ≥ 65 years of age.

• Unwillingness to participate.
• Cognitive barriers which would make it difficult to participate in discussion.
• Non-English speaking.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/10/23. Questions regarding updates should be directed to the study team contact.

• Adult men and women, age 18 or older.
• Previously seen at the Mayo Clinic Fibromyalgia and Chronic Fatigue Clinic (Rochester, MN) and diagnosed with fibromyalgia.
• Able to read and speak English.
• Must be willing and able to provide consent and participate in both portions of the study.

• Minors (under the age of 18).
• Patients not diagnosed with fibromyalgia.
• Patients who cannot provide consent or unwilling to participate in both portions of the study.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 4/27/23. Questions regarding updates should be directed to the study team contact.

• The subject has signed the IRB approved Informed Consent Form (ICF) specific to this study prior to enrollment.
• Male or female, ≥ sixty-five (65) years of age.
• Positive diagnostic imaging by MRI within 9 months of enrollment of the index shoulder indicating a full thickness MRCT:
  • Measuring ≥ 5 cm in diameter;
  • Involving ≥ two tendons.
• Functional deltoid muscle and preserved passive range of motion on physical examination.
• Documented VAS score > 30 mm pain.
• Failed non-operative treatment of at least 3 months from the initial treatment to include one or more of the following:
  • Oral analgesics;
  • Anti-inflammatory medication (e.g., ibuprofen, naproxen);
  • Corticosteroid injection(s);
  • Physical therapy;
  • Activity modification;
  • Rest (sling used) or activity modification.
• Must be able to read and understand the approved Informed Consent Form (written and oral).
• Must be in general good health (as determined by the Investigator) based on screening assessments and medical history.
• Must be independent, ambulatory, and can comply with all postoperative evaluations, visits, and electronic database collection.

Intra-operative

• Full thickness tear.
• Tear size ≥ 5 cm in diameter.
• Tear involving ≥ two tendons.

• Known allergy to the device material (copolymer of PLA (poly (lactic acid) and -ε-caprolactone).
• Evidence of the following conditions:
  • Severe gleno-humeral or acromio-humeral arthritis
  • Full thickness cartilage loss as seen on MRI
  • History within the past 5 years of anterior or posterior shoulder subluxation or dislocation as determined by history, examination, or radiographic findings
  • Pre-existing deltoid defect or deltoid palsy
  • Major joint trauma, infection, or necrosis
  • Partial thickness tears of the supraspinatus
  • Fully reparable rotator cuff tear [tear of less than 5 cm in diameter (or < 4 cm^2) with retractable tendon that can be fully repaired];
  • Known neurovascular compromise;
  • Complete deltoid muscle palsy;
  • Traumatic muscle tears of the pectoralis or deltoid.
• The subject requires concomitant:
  • Subscapularis repair;
  • Labral repair of any type;
  • Biceps tenodesis.
• Previous surgery of the index shoulder in the past 1 year, excluding diagnostic arthroscopy.
• The subject’s condition is bilateral and rotator cuff repair is scheduled or to be scheduled over the course of this study for the contra lateral shoulder.
• Major medical condition that could affect quality of life and influence the results of the study (e.g., rheumatoid arthritis).
• The subject has documented evidence of a history (e.g., liver testing) of drug/alcohol abuse within 12 months of enrollment.
• The subject’s condition represents a worker’s compensation case.
• The subject is currently involved in a health-related litigation procedure.
• Females of child-bearing potential who are pregnant or plan to become pregnant.
• Concurrent participation in an investigational clinical study one month prior to enrollment or during the entire study period.
• The subject is physically or mentally compromised (e.g., currently being treated for a psychiatric disorder, senile dementia, Alzheimer’s disease,etc.), to the extent that the Investigator judges the subject to be unable or unlikely to remain compliant to follow-up.
• The subject is receiving prescription narcotic pain medication for conditions unrelated to the index shoulder condition.
• The subject currently has an acute infection in the area surrounding the surgical site.
• Baseline WORC score less than 420.

Intra-operative

• Rotator cuff is/presents with:
  • Fully reparable with adequate tissue and muscle quality (equivalent to Goutallier stage 1 or 2);
  • Partial thickness tear of the supraspinatus;
  • Evidence of significant osteoarthritis.
• The subject requires concomitant:
  • Subscapularis repair;
  • Labral repair of any type;
  • Biceps tenodesis.
• Coracoacromial ligament functional deficiency or shoulder instability is identified.

All potential subjects screened for eligibility will be listed on the Screening and Enrollment Log. The Screening and Enrollment Log will document the date of screening, the results of screening, and the primary reason for excluding the subject (e.g., does not satisfy eligibility criteria or subject declined).

Subjects who are eligible to enter the study will be provided with an Institutional Review Board (IRB) approved Informed Consent Form (ICF) for review and signature. Each subject will have a physical exam of the index shoulder that incorporates a medical history and injury etiology. Diagnosis of the rotator cuff tear will be confirmed with MRI acquired within 9 months of enrollment.

• Signed informed consent obtained before any trial-related procedures at screening.
• Subject aged ≥ 18 years old at screening.
• Medical record documentation of recurrent Clostridioides difficile infection (rCDI) per the trial definition that includes ≥ 1 recurrence after a primary C. difficile infection (CDI) episode, at screening.
• Stool test positive for the presence of toxigenic C. difficile or C. difficile toxin for the qualifying rCDI episode, documented at the time of CDI diarrhea, at screening.
• Eligible for fecal microbiota transplantation (FMT) as judged by the investigator or current treatment guidelines for rCDI in the United States (US).
• Candidate for colonoscopy as judged by the investigator.
• Currently taking or have just received a prescription for a course of antibiotics to ensure control of CDI-related diarrhea, at screening. The antibiotic course should be for a minimum of 10 consecutive days, and a maximum of 30 days in total (including intermittent dosing/pulse) before the antibiotic washout period.
• Adherence to at least one of the following conditions throughout the trial period:
  • The subject, if female, must:
    • Be post-menopausal (women ≥ 45 years with no menstrual period for ≥ 12 months without an alternative medical cause); or
    • Have been surgically sterilized; or
    • Have had a hysterectomy prior to screening; or
    • Use an adequate method of contraception (i.e., implants, injectables, hormonal intrauterine devices, combined hormonal contraceptives, having a vasectomized sexual partner, or total abstinence from heterosexual relations with no plans of becoming pregnant through insemination or in vitro fertilization).
  • The subject, if male, must:
    • Use a non-hormonal single-barrier contraception (i.e., condom); and
    • Use an adequate method of contraception if his female partner is of childbearing potential (i.e., not post-menopausal) as defined above;
      • This is however not required if the male subject is documented surgically sterile, remains sexually abstinent, when this is in line with his preferred and usual lifestyle, or if he has a female partner who is surgically sterilized, had a hysterectomy, or is post-menopausal. 
• Willing to abstain from consuming probiotics (including over-the-counter and prescription) from screening through 8 weeks after RBX2660 treatment.
• Willing to comply with trial procedures, including attending scheduled visits, completion of the electronic stool diary, providing stool samples for future exploratory research, and adherence to treatment plan.

• Use or planned use of systemic antibiotics for an indication other than the qualifying rCDI episode.
• Current disease symptoms (e.g., diarrhea) caused by a confirmed intestinal pathogen other than C. difficile.
• Current uncontrolled chronic diarrhea not related to CDI.
• Current refractory CDI, i.e., CDI diarrhea not improving with antibiotics used to treat CDI.
• Fecal microbiota transplantation, treatment with other microbiota-based therapies, or treatment with RBX2660 other than the IMP:
  • Within 6 months before screening; or
  • Between screening and baseline.
• Receipt of CDI vaccine or treatment with CDI monoclonal antibodies:
  • Within 12 months before screening; or
  • Between screening and baseline.
• Compromised immune system including, but not limited to, inherited/primary and acquired immune disorders as judged by the investigator.
• Solid-organ transplant recipient.
• Initiation or escalation of systemic immunosuppressive agents, at the discretion of the investigator, for any condition:
  • During the 8 weeks before screening; or
  • Between screening and baseline.
    • Subjects on a stable dose of systemic immunosuppressants (e.g., ≤20 mg/day prednisone equivalent daily dose) may be considered eligible at the discretion of the investigator.
• Current or planned therapy that may cause diarrhea.
• Current or planned systemic cancer treatment (e.g., chemotherapy, radiotherapy, or other).
• Diagnosis of short bowel syndrome.
• Current uncontrolled gastrointestinal motility disorders.
• Evidence of active, severe, or fulminant colitis.
• Diagnosis of toxic megacolon.
• Have a current colostomy or ileostomy.
• Major gastrointestinal tract surgery (this does not include appendectomy or cholecystectomy):
  • Within 60 days before screening; or
  • Between screening and baseline.
• Planned surgery requiring perioperative antibiotics.
• Life expectancy of < 6 months, as judged by the investigator at screening.
• Current abuse of alcohol or drugs, as judged by the investigator at screening.
• Pregnant (as confirmed by a positive pregnancy test), breastfeeding, or intending to become pregnant, during trial participation.
• Participation in any interventional clinical trial during the past 12 weeks before screening.
• Known or suspected hypersensitivity to polyethylene glycol 3350.
• Inability to participate in the trial for other reasons, as judged by the investigator at screening.

Eligibility last updated 10/13/22. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/19/23. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 4/27/23. Questions regarding updates should be directed to the study team contact.

• Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that are not part of standard of care for the patient's disease.
• Age ≥ 18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 12 weeks.
• Measurable disease as per RECIST 1.1 and documented by CT and/or MRI.
• All tumors must have histologically or cytologically confirmed cancer diagnosis.
• Patients must have any of the following cancers to be eligible:
  • Colorectal cancer
    • Histologically or cytologically documented adenocarcinoma of colon or rectum at the time of initial presentation;
    • Metastatic or locally advanced/unresectable disease;
    • Documented disease progression after the last administration of  standard therapies or intolerance to at least 2 prior systemic treatment regimens (CUE-102 will be 3rd line therapy or greater).
  • Gastric cancer (including gastroesophageal junction)
    • Histologically or cytologically documented gastric cancer at the time of initial  presentation;
    • Metastatic or locally advanced/ unresectable disease;
    • Documented disease progression after last administration of standard therapies or intolerance to standard therapies. (CUE-102 will be 2nd line therapy or greater).
  • Pancreatic cancer
    • Histologically or cytologically documented pancreatic adenocarcinoma at the time of initial presentation;
    • Patients with metastatic or locally advanced/unresectable disease;
    • Prior systemic treatment must include either a fluoropyrimidine-based or gemcitabine-based regimen in either the (neo)adjuvant or relapsed setting (CUE-102 will be 2nd line therapy or greater).
  • Ovarian cancer
    • Histologically or cytologically documented ovarian cancer at the time of initial presentation;
    • Metastatic or locally advanced/unresectable disease, with documented disease  progression after last administration of standard therapies or intolerance to standard therapies;
    • Prior systemic treatment must include a platinum-based regimen. (CUE-102 will be 2nd line therapy or greater);
    • For patients determined to have platinum-sensitive disease, treatment with a second platinum-based combination regimen +/- bevacizumab should be considered prior to treatment with CUE-102 (CUE-102 will be 3rd line therapy or greater).
• Patient must have HLA-A*0201 genotype as determined by genomic testing.
• Patient must have histologically and/or cytologically proven tumor(s) that is WT1 positive.
• Acceptable laboratory parameters.
• Female patients of childbearing potential must agree to use acceptable contraceptive measures from the time of main study consent through 90 days after discontinuation of study drug administration.
• Non-vasectomized male patients with partners of childbearing potential must use barrier contraception from the time of main study consent through 90 days after discontinuation of study drug.
• Patients who have previously received an immune CPI (e.g., anti-programmed cell death ligand 1 (anti PD-L1), anti-programmed cell death 1 (anti-PD-1), anti-cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) prior to enrollment must have toxicities related to the CPI resolved to CTCAE ≤ Grade 1 or baseline (level prior to the CPI) to be eligible for enrollment. Patients who have experienced CPI-related endocrinopathies (e.g., diabetes, adrenal insufficiency) may participate if endocrinopathies are controlled (CTCAE ≤ Grade 1) with endocrinology support and appropriate repletion.
  • Note: Patients who experienced previous hypothyroidism toxicity on a CPI are eligible to enter study regardless of CTCAE grade resolution as long as the patient is well controlled on thyroid replacement hormone.

• Female patients who are pregnant or plan to become pregnant during the course of the trial.
• Female patients who are breastfeeding.
• Patients with symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic, and not have any of the following at the time of enrollment:
• Need for concurrent treatment for the CNS disease (e.g., surgery, radiation, corticosteroids > 10 mg prednisone/day or equivalent);
• Progression of CNS metastases on CT or MRI for at least 28 days after last day of prior therapy for the CNS metastases;
• Concurrent leptomeningeal disease or cord compression;
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or  immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is permitted;
• History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation;
• Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 14 days (or 28 days, for antibody drugs), before the first dose of CUE-102;
• Treatment with radiation therapy within 14 days before the first dose of CUE-102;
• Treatment with corticosteroids (> 10 mg per day prednisone or equivalent) or other immune suppressive drugs within 14 days before the first dose of CUE-102. Steroids for topical, ophthalmic, inhaled, or nasal administration are permitted. Physiological replacement with up to a maximum dose of 5 mg equivalence of prednisone per day is permitted;
• History of clinically significant cardiovascular disease; 
• Clinically significant pulmonary compromise (e.g., requirement for supplemental oxygen);
• Clinically significant gastrointestinal (GI) disorders.
• Patients who experienced the following immune CPI-related AEs are ineligible even if the AE resolved to ≤ Grade 1 or baseline:
  • ≥ Grade 3 ocular AE;
  • Changes in liver function tests that met the criteria for Hy's Law (> 3 × ULN of either ALT/AST with concurrent > 2 × ULN of total bilirubin (total and direct) and without alternate etiology);
  • ≥ Grade 3 neurologic toxicity;
  • ≥ Grade 3 colitis;
  • ≥ Grade 3 renal toxicity.
• Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days before the first dose of CUE-102.
• No known history of infection or positive test for HIV, Hepatitis B or Hepatitis C, testing prior to enrollment is not required unless mandated by local authority.
• Second primary invasive malignancy that has not been in remission for > 2 years.
• History of trauma or major surgery within 28 days before the first dose of CUE-102.
• Any serious underlying medical or psychiatric condition that would impair the ability of the patient to receive or tolerate the planned treatment at the investigational site.
• Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the drug formulation for CUE-102.
• Vaccination with any live virus vaccine within 28 days before the first dose of CUE-102. Inactivated annual influenza vaccination is allowed.
• Dementia or altered mental status that would preclude understanding and rendering of informed consent.
• Active or history of significant alcohol or other substance abuse within 1 year before the first dose of CUE-102.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 7/29/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 1/23/23. Questions regarding updates should be directed to the study team contact.

• Able to speak and read English or Spanish (for patients enrolled at MD Anderson and Mayo Clinic), English or Korean (for patients enrolled at Yonsei), and English or Japanese (for patients enrolled at Keio).
• Patients with a biopsy-confirmed diagnosis of non-metastatic gastric or GEJ adenocarcinoma, who are scheduled to undergo MIPG or MITG for curative-intention.
• Age ≥ 18.

• Patients with known malabsorption syndromes or a lack of physical integrity of the upper gastrointestinal tract.
• Patients with known narcotic dependence, with average daily dose > 5 mg oral morphine equivalent.
• Subjects deemed unable to comply with study and/or follow-up procedures, at investigators' discretion.
• Patients who are pregnant (since are excluded from receiving standard-of-care MIPG or MITG).

Eligibility last updated 4/26/22. Questions regarding updates should be directed to the study team contact.

• Any patient with Barrett's Esophagus (BE) and  Low-grade Dysplasia (LGD) who provides informed consent AND meets all the following criteria will be eligible for enrollment.
• Male or female, age ≥ 18 years.
• Subject has endoscopic evidence of BE characterized by the presence of salmon-colored mucosa in the tubular esophagus of at least 1 cm in length as well as endoscopic biopsies from the involved areas demonstrating columnar metaplasia with goblet cells. This inclusion criterion will exclude patients with intestinal metaplasia with dysplasia of the gastric cardia.
• Biopsies within the previous 12 months demonstrating BE and LGD.
• Confirmation of LGD by expert central pathology panel from biopsies obtained within the previous 12 months (including those obtained from the referring physician).
• Demonstrated ability to tolerate PPI therapy based on patient self-report; and;
  • Ability to discontinue antiplatelet and anticoagulant therapy based on standard guideline recommendations prior to and after endoscopic procedures.24.
• We will include non-English speaking patients based on the geographic locations of our sites and the single IRB of record will be responsible for the approval of certified-translated consents.

*

• Pregnancy.
• Prior EET for BE.
• History of HGD or EAC.
• History of esophageal resection or esophagectomy.
• Active erosive esophagitis (Los Angeles Grade B or higher)
  •patients are eligible upon resolution of erosive esophagitis.
• Esophageal strictures precluding passage of the endoscope or treatment catheters – patients are eligible upon resolution of esophageal stricture due to endoscopic dilation or resolution with medical therapy.
• Esophageal varices or known portal hypertension; and;
  • Life expectancy of < 2 years as judged by the site investigator.

*  Patients are eligible for enrollment and randomization if they meet the above eligibility criteria. It should be noted that the presence of a visible lesion (nodularity) at the index endoscopy is not an exclusion criterion.  Those with visible lesions will undergo endoscopic mucosal resection (EMR) to determine pathology. If HGD or EAC pathology is determined, then the subject will exit from the study after a 30-day safety follow up.

Eligibility last updated 7/18/22. Questions regarding updates should be directed to the study team contact.

• ≥ 18 years of age.
• Second or third trimester of healthy pregnancy.
• Meet all tissue donor eligibility criteria (as defined by 21 CFR 1271 donor eligibility criteria).
• Planning to deliver her infant at Mayo Clinic Rochester via Cesarean Section.
• Able and willing to provide written informed consent.

• Failure to meet 21 CFR 1271 donor eligibility criteria based on responses to a Tissue Donor History Questionnaire (administered at the time of enrollment), including but not limited to: history of malignancy (including melanoma and any form of other skin cancer <6 months from diagnosis*), transplant, long-term use of steroids, autoimmune disorders, or chronic infections such as HIV, Hepatitis, TB, MRSA etc.
• Positive infectious disease result on any test in the infectious disease screening panel collected during Visit 1 or post-operatively with the exception of CMV** (including HBsAg Screen, HBc Total Ab, HBV NAT, HCV NAT, HIV-1 NAT, HCV Ab Screen, HIV-1/-2, plus O Ab Screen, HTLV-I/-II Ab Screen, T. cruzi Total Ab, Syphilis Ab Screen, West Nile Virus NAT, ZIKA NAT).
• Abnormal pregnancy that may include:
  • Birth defects of the fetus;
  • Maternal complications with the placenta or umbilical cord anatomy;
  • Any complications during the birthing process.
• Vaginal delivery.
• Excluded after medical records review or physical exam.

NOTE: Enrolled subjects will be excluded from the study if, at the time of delivery, any of the below occur. In these situations, tissue and cord blood will not be collected, and the subject will be withdrawn from the study. Tissue will be given to clinical pathology for review post-delivery as standard procedure.

Exclusion Criteria Post Enrollment:   

• Placentas with Apgar test < 7 at 5 minutes.
• Gestation period of < 37 weeks.
• Multiple gestation (twins or greater).
• Suspected chorioamnionitis.
• Time between membrane rupture and delivery > 18 hours.
• Any significant fetal medical history including: stillborn, respiratory distress, ominous heart tracing, fetal anomaly, oligohydramnios, transfer to NICU, and IUG.
• Any significant maternal medical history including: recurrent reproductive complications, unexplained maternal fever, collagen vascular disease, hypertension/preeclampsia, diabetes, and substance abuse.
• Unusual anatomic findings (placental mass, true knots, or unusual findings per the obstetrician).
• SARS-CoV-2 (COVID-19) infection during pregnancy.

* Melanoma is excluded, any skin cancer diagnosis > 6 months from resection is acceptable.

**Donors who test positive for CMV will remain eligible for participation. Should MSCs and/or derivatives of be successfully isolated and included in the biorepository, a disclaimer disclosing positive CMV status of the tissue donor will be included on the Certificate of Analysis for future considerations. 

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 9/5/23. Questions regarding updates should be directed to the study team contact.