• Previously participated in a prior study and expressed willingness to be recontacted or who respond to intramural and extramural adverts.
• We propose three groups: 10 individuals who have NFG/NGT, 10 individuals with prediabetes (IGT) and 10 individuals with type 2 diabetes (T2DM).

• Medications that can affect glucose metabolism (to be determined by PI) or in the case of participants with T2DM taking pioglitazone.
• For female subjects: positive pregnancy test.
• Any active systemic illness.
• Upper gastrointestinal surgery.

Eligibility last updated 8/20/21. Questions regarding updates should be directed to the study team contact.

• Inpatients or outpatients.
• Voluntary clinical patient with the capacity to assent (or consent if 18) to treatment and a parent or legal  guardian with the capacity to consent (if younger than 18).
• Biological female or male (nonbinary or other gender identities are not exclusionary).
• 12-18 years of age.
• Diagnosed with MDD based on Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) criteria with the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) in subjects 12-17 years of age; The Mini-International Neuropsychiatric Interview will be used for subjects who are 18 years of age.
• In a current episode of MDD with duration of at least 4 weeks but less than 3 years.
• Depressive symptom severity as demonstrated by CDRS-R total composite score of forty or greater and a suicidal ideation score of 3 or more on item 13 of the CDRS-R.
• A minimum score of 1 (“wish to be dead”) on the C-SSRS severity of ideation subscale.
• Demonstrating that depressive symptom severity as evaluated at the screening visit does not improve between screening and baseline by 25% or more.
• Eligible for transcranial magnetic stimulation (TMS) based on safety criteria.
• On a medically acceptable form of birth control during the 10 day acute treatment course if female and of child bearing potential.
• Taking an antidepressant medication if recommended by the referring clinician and agreed upon by parents and patients. Please note that patients are not required to take an antidepressant medication for study participation for practical, ethical, and human subject protection concerns. Medication status and prior treatment resistance will be carefully recorded with the Antidepressant Treatment History Form criteria for relevant statistical considerations.

• Diagnosis of a psychotic disorder, bipolar disorder, anorexia nervosa, bulimia nervosa, substance use disorders within the past year (with the exception of caffeine and tobacco).
• Lifetime diagnosis of a psychotic disorder confirmed by a research screening interview (including schizophrenia, major depressive disorder with psychotic features, and bipolar disorder with psychotic features).
• Intelligent quotient less than 70 (if there is a clinical concern, subjects will be psychometrically assessed with the Slosson Intelligence Test, Revised).
• Positive urine drug screen at baseline.
• Patients with a history of epilepsy or unexplained seizures.
• Any family history of epilepsy.
• Patients medicated with drugs lowering the seizure threshold (examples: neuroleptic agents and tricyclic antidepressants).
• History of any treatment with electroconvulsive therapy or TMS.
• Use of any investigational drug within 4 weeks of baseline.
• Prior brain surgery.
• Risk for increased intracranial pressure such as a brain tumor.
• Life-time history of head trauma with loss of consciousness for greater than 5 minutes duration.
• Any true positive findings on the TMS safety screening form (TASS).
• Pregnant or nursing patients.
• Conductive, ferromagnetic, or other magnetic-sensitive metals implanted in the head within. 30 cm of the treatment coil excluding the mouth that cannot be safely removed (examples include cochlear implants, vagus nerve stimulators, deep brain stimulators, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry and hair barrettes).
• Patients with any implanted stimulators or implants controlled by physiologic signals, including VNS, SCS, PNS, defibrillators and pacemakers.
• Patients with neurological conditions that include a history of seizures, cerebrovascular disease, cerebral aneurysm, dementia, movement disorders, having a history of repetitive or severe head trauma, or with primary or secondary tumors in the CNS.
• Patients with a history of increased intracranial pressure, history of severe headaches within the previous 1 year, or severe head trauma.
• Implanted medication pumps and cardiac pacemakers.
• Patients suffering from vascular, traumatic, tumoral, infectious, or metabolic lesions of the brain, even without a history of seizure, or without anticonvulsant medication.
• Patients with an unstable medical illness (other than depression).
• Inability to adhere to the protocol.

Eligibility last updated 1/20/22. Questions regarding updates should be directed to the study team contact.

• Age 3 to 17.5 years.
• If the child wears contact lenses, the child must be able to perform all testing (in office and at home) in spectacle correction without contact lenses.

Eligible families will:

• Have an iPhone 6 or a later version (excluding first generation iPhone SE) with them at the office visit.
• The iPhone screen must not have cracks or damage that would decrease legibility of the letters presented (The screen will be checked by a study team member to assure there is no screen damage that would affect legibility of optotypes).
• Be able to successfully download the age appropriate (ATS-HOTV or e-ETDRS) iPhone application to their iPhone, with assistance from office staff, if needed.
• Successfully perform the phone-based VA test at the enrollment visit with the participant wearing his/her current optical correction (if worn), with assistance from office staff, if needed.
• Be able to use the same iPhone to measure VA at home.
• Be able to have the same adult administer the home VA test for all required home VA tests.
• Be able and willing to test VA at home 3 days after enrollment (Home test 1) and 1 day after Home test 1 (Home test 2).
• Be willing to test VA at home within 2 days prior to a subsequent return office visit 3 months after enrollment.
• Be willing to return for a 3-month office visit.

Participant

• Use of atropine in the last 30 days, including the day of enrollment.
• Use of atropine expected in the upcoming four months.
• Aphakia (one or both eyes).
• Dilation and cycloplegia within 48 hours of the first in-office VA measure.
• Any cognitive or physical limitations of the participant or parent that would limit their.
• Ability to perform the phone-based testing at home or in-office testing.

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

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

• Ability to provide informed consent.
• 40 patients:
  • 20 preoperative THA, 20 postoperative THA;
  • Sex: 20 men, 20 women;
  • Age: 20 patients ≥ 70 years, 10 patients 50-70 years, 10 patients 18-50 years.

• Patients with lumbosacral hardware, contralateral THA.

Eligibility last updated 11/5/21. Questions regarding updates should be directed to the study team contact.

• Pathologically proven diagnosis of extensive stage small cell lung cancer.
• Partial response (PR) or stable disease (SD) after 4-6 cycles of etoposide/platinum (E/P) doublet plus atezolizumab by re-staging scans (positron emission tomography [PET]/computed tomography [CT] scan, diagnostic CT scan, magnetic resonance imaging [MRI] optional per treating physician); atezolizumab should continue through randomization. Patients must be randomized within 9 weeks of last dose of etoposide/platinum or 6 weeks from completion of prophylactic cranial irradiation (PCI).
• At the time of enrollment, patients must have had measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST]) and 3 or fewer observable liver metastases and no evidence of progressive disease (per RECIST) at time of enrollment.
• Patients presenting with a pleural effusion will be eligible if thoracentesis is cytologically negative and non-bloody or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging.
• Appropriate stage for study entry based on the following diagnostic workup:
  • History/physical examination within 14 days prior to registration;
  • Imaging within 42 days prior to registration to include:
    • MRI brain with contrast or CT brain with contrast;
    • CT chest, abdomen and pelvis or whole body PET/CT scan after the fourth cycle of chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of registration.
• Absolute neutrophil count (ANC) ≥ 1,000/cells/mm^3 (within 14 days prior to registration).
• Platelets ≥ 75,000 cells/mm^3 (within 14 days prior to registration).
• Hemoglobin ≥ 8 g/dL (within 14 days prior to registration).
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 14 days prior to registration).
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3.0 x ULN (AST and/or ALT ≤ 5 ULN for patients with liver involvement) (within 14 days prior to registration).
• Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 ULN for patients with documented liver involvement or bone metastases) (within 14 days prior to registration).
• Adequate renal function ≤ 2.0 x ULN.
• Adequate renal function within 30 days prior to registration defined as follows: glomerular filtration rate (GFR) ≥ 40 mL/min/1.73 m^2.
• Upfront central nervous system (CNS) radiotherapy for treatment of brain metastases is permitted provided there is no evidence of CNS progression at the time of randomization and patients are clinically stable on a dose of steroids < 10 mg prednisone a day or equivalent. Upfront radiation therapy of symptomatic metastatic site is permissible if causing patient pain or impending fracture.
• Patients with bone metastases are eligible. However, to assess response after radiation for bone metastases, must order at least diagnostic CT scan to measure response.
• For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to registration.
  • Note: Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
    • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy);
    • Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.

• Metastatic disease invading the liver (> 3 metastases), heart or > 10 metastatic sites detectable after induction systemic therapy. Each visible bone metastasis on radiographic scan count as one site. For site of bony metastases, must order diagnostic CT scan for assessment of response.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 5 years prior to randomization. Cancers with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome are eligible (such as adequately treated carcinoma in situ of the cervix or oral cavity; localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent).
• Prior radiotherapy except in the thorax, where there may be some overlap in the mediastinum and spine, as long as overlap fields meet dose constraints.
• History of autoimmune disease, including, but not limited to: systemic lupus erythematosus; rheumatoid arthritis; inflammatory bowel disease (e.g., Crohn's, ulcerative colitis); vascular thrombosis associated with antiphospholipid syndrome; Wegener's granulomatosis; Sjogren's syndrome; Guillain-Barre syndrome; multiple sclerosis; vasculitis; or glomerulonephritis.
  • Note: the following are eligible:
    • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible;
    • Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible;
• Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must not have ocular manifestations within the past year;
  • Rash must cover less than 10% of body surface area (BSA);
  • Disease is well controlled on topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%).
• No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors or oral steroids).
• Severe, active co-morbidity defined as follows:
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
  • Active tuberculosis;
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.
• Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). (The HCV RNA test must be performed for patients who have a positive HCV antibody test).
• Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL).
• Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have:
  • A stable regimen of highly active anti-retroviral therapy (HAART);
  • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections;
  • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests.
• Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of > 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary.
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months.
• History of recent myocardial infarction within 6 months prior to registration.
• Clinically significant interstitial lung disease.
• Pregnancy:
  • Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 5 months (150 days) after the last dose of study agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately;
  • Women who are breastfeeding and unwilling to discontinue.
• History of allogeneic organ transplant.
• Patients who have had immunotherapy-induced pneumonitis.

• Pathologically proven diagnosis of extensive stage small cell lung cancer.
• Partial response (PR) or stable disease (SD) after 4-6 cycles of etoposide/platinum (E/P) doublet plus atezolizumab by re-staging scans (positron emission tomography [PET]/computed tomography [CT] scan, diagnostic CT scan, magnetic resonance imaging [MRI] optional per treating physician); atezolizumab should continue through randomization. Patients must be randomized within 9 weeks of last dose of etoposide/platinum or 6 weeks from completion of prophylactic cranial irradiation (PCI).
• At the time of enrollment, patients must have had measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST]) and 3 or fewer observable liver metastases and no evidence of progressive disease (per RECIST) at time of enrollment.
• Patients presenting with a pleural effusion will be eligible if thoracentesis is cytologically negative and non-bloody or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging.
• Appropriate stage for study entry based on the following diagnostic workup:
  • History/physical examination within 14 days prior to registration;
  • Imaging within 42 days prior to registration to include:
    • MRI brain with contrast or CT brain with contrast;
    • CT chest, abdomen and pelvis or whole body PET/CT scan after the fourth cycle of chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of registration.
• Absolute neutrophil count (ANC) ≥ 1,000/cells/mm^3 (within 14 days prior to registration).
• Platelets ≥ 75,000 cells/mm^3 (within 14 days prior to registration).
• Hemoglobin ≥ 8 g/dL (within 14 days prior to registration).
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 14 days prior to registration).
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3.0 x ULN (AST and/or ALT ≤ 5 ULN for patients with liver involvement) (within 14 days prior to registration).
• Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 ULN for patients with documented liver involvement or bone metastases) (within 14 days prior to registration).
• Adequate renal function ≤ 2.0 x ULN.
• Adequate renal function within 30 days prior to registration defined as follows: glomerular filtration rate (GFR) ≥ 40 mL/min/1.73 m^2.
• Upfront central nervous system (CNS) radiotherapy for treatment of brain metastases is permitted provided there is no evidence of CNS progression at the time of randomization and patients are clinically stable on a dose of steroids < 10 mg prednisone a day or equivalent. Upfront radiation therapy of symptomatic metastatic site is permissible if causing patient pain or impending fracture.
• Patients with bone metastases are eligible. However, to assess response after radiation for bone metastases, must order at least diagnostic CT scan to measure response.
• For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to registration.
  • Note: Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
    • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy);
    • Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.

• Metastatic disease invading the liver (> 3 metastases), heart or > 10 metastatic sites detectable after induction systemic therapy. Each visible bone metastasis on radiographic scan count as one site. For site of bony metastases, must order diagnostic CT scan for assessment of response.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 5 years prior to randomization. Cancers with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome are eligible (such as adequately treated carcinoma in situ of the cervix or oral cavity; localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent).
• Prior radiotherapy except in the thorax, where there may be some overlap in the mediastinum and spine, as long as overlap fields meet dose constraints.
• History of autoimmune disease, including, but not limited to: systemic lupus erythematosus; rheumatoid arthritis; inflammatory bowel disease (e.g., Crohn's, ulcerative colitis); vascular thrombosis associated with antiphospholipid syndrome; Wegener's granulomatosis; Sjogren's syndrome; Guillain-Barre syndrome; multiple sclerosis; vasculitis; or glomerulonephritis.
  • Note: the following are eligible:
    • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible;
    • Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible;
• Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must not have ocular manifestations within the past year;
  • Rash must cover less than 10% of body surface area (BSA);
  • Disease is well controlled on topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%).
• No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors or oral steroids).
• Severe, active co-morbidity defined as follows:
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
  • Active tuberculosis;
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.
• Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). (The HCV RNA test must be performed for patients who have a positive HCV antibody test).
• Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL).
• Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have:
  • A stable regimen of highly active anti-retroviral therapy (HAART);
  • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections;
  • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests.
• Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of > 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary.
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months.
• History of recent myocardial infarction within 6 months prior to registration.
• Clinically significant interstitial lung disease.
• Pregnancy:
  • Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 5 months (150 days) after the last dose of study agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately;
  • Women who are breastfeeding and unwilling to discontinue.
• History of allogeneic organ transplant.
• Patients who have had immunotherapy-induced pneumonitis.

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

Eligibility last updated 4/12/23. Questions regarding updates should be directed to the study team contact.

• Male and female patients must be at least 18 years of age at the time of signing the informed consent:
  • Male patients and female partners must agree to use contraception starting 4 weeks prior to the first dose of IP, during the treatment period, and for at least 100 days after the last dose of IP. Male patients must refrain from donating sperm during this period;
  • Female patients of childbearing potential must agree to use contraception starting at Screening, during the treatment period, and for at least 4 weeks after the last dose of IP.
• Body mass index (BMI) ≥ 18 kg/m^2 and ≤ 40 kg/m^2.
• Patients with symptomatic PAH belonging to one of the following 2018 Clinical Group 1 Sub-types:
  • Idiopathic PAH;
  • Heritable PAH;
  • Drug- or toxin- induced.
• PAH associated with:
  • Connective tissue disease.
• Congenital systemic to pulmonary shunt (atrial septal defect, ventricular septal defect, patent ductus arteriosus) repaired at least one year prior to Screening.
• Human Immunodeficiency Virus (HIV) infection
  •if diagnosed with HIV, must have stable disease status defined as follows:
  • stable treatment with HIV medications for at least 8 weeks prior to Screening;
  • no active opportunistic infection during the Screening Period;
  • no hospitalizations due to HIV for at least 4 weeks prior to Screening.
• WHO FC II or III.
• Confirmed diagnosis of PAH and meet all the following hemodynamic criteria by means of a screening RHC completed prior to randomization:
  • mPAP of ≥ 20 mmHg;
  • PVR ≥ 350 dyne•sec/cm^5;
  • Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of ≤ 12 mmHg if PVR ≥ 400 and < 500 dyne•sec/cm^5, or PCWP/LVEDP ≤ 15 mmHg if PVR ≥ 500 dyne•sec/cm^5;
  • 6MWD of 100 to 550 meters at Screening.
• Currently on a stable treatment regimen with one or more treatments approved for PAH. Stable therapy is defined as receiving the same medication(s) for ≥ 12 weeks prior to the screening RHC and at a stable dose level for each for ≥ 8 weeks prior to the  screening RHC. Any instances where doses of a medication have been missed prior to RHC must be discussed with the Medical Monitor prior to performing the RHC.
• Meet all of the following criteria determined by pulmonary function tests completed no more than 24 weeks prior to Screening (performed with or without bronchodilation):
  • Forced expiratory volume in one second (FEV1) ≥ 60% of predicted normal; and
  • Total lung capacity (TLC) ≥ 70% of predicted normal or FVC ≥ 70% predicted if TLC is not available; For subjects with CTD associated PAH, if TLC is ≥ 60% of predicted but < 70% of predicted of if FVC ≥ 60% or predicted but < 70% of predicted, high resolution computed tomography [HRCT] obtained within 6 months of screening may be utilized to demonstrate limited interstitial lung disease.
• If participating in an exercise program for pulmonary rehabilitation, the program must have been initiated ≥ 12 weeks prior to Screening, and patient must agree to maintain the current level of rehabilitation for the first 24 weeks of IP. If not participating in an exercise training program for pulmonary rehabilitation, must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 24 weeks of IP.
• Willing and able to give written informed consent and to comply with the requirements of the study for its duration. 

• Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception.
• WHO Pulmonary Hypertension (PH) Group 1 PAH associated with portal hypertension or schistosomiasis; PH due to left heart disease (WHO PH Group 2), lung diseases and/or hypoxia (WHO PH Group 3), chronic thromboembolic pulmonary hypertension (WHO PH Group 4), or PH with unclear multifactorial mechanisms (WHO PH Group 5).
• PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), pulmonary capillary hemangiomatosis, portal hypertension, or unrepaired congenital heart defects (CHD)
• Three or more of the following risk factors for left ventricular disease:
  • BMI > 30 kg/m^2;
  • Diagnosis of essential hypertension that is actively treated;
  • Diabetes mellitus;
  • History of significant coronary artery disease (e.g., chronic stable angina, history of coronary intervention within the last 3 months, or a stenosis > 70% at coronary angiography);
  • Atrial fibrillation;
  • Left atrial volume index > 41 mL/m^2.
• Known genetic hypertrophic cardiomyopathy.
• Known cardiac sarcoidosis or amyloidosis.
• The patient has a history of, or currently has, a constrictive cardiomyopathy.
• Known history of any LVEF < 40% by echocardiogram within 3 years of randomization (Note: a transient decline in LVEF below 40% that occurred and recovered more than 6 months before the start of Screening and was associated with an acute intercurrent condition [e.g., atrial fibrillation] is allowed).
• Hemodynamically significant valvular heart disease as determined by the Investigator, including:
  • greater than mild aortic and/or mitral stenosis; and/or
  • severe mitral and/or aortic regurgitation (> Grade 3).
• Severe arthritis, musculoskeletal problems, or morbid obesity that, in the opinion of the Investigator, is the cause of the patient’s functional limitation and would affect the patient’s ability to perform or complete the 6MWT.
• Planned major surgery within the next 3 months, including lung transplantation, major abdominal or major intestinal surgery
• End stage renal disease defined as receiving peritoneal dialysis, hemodialysis, or status after renal transplantation; or severe liver disease defined as Child-Pugh Class C, with or without cirrhosis
• Known congenital long QT syndrome (LQTS) or known family history of LQTS
• Depression that is currently rated as severe (defined as a score of ≥ 16 on the QIDS-C and/or Hospital Anxiety and Depression Scale [HADS] Depression and/or Anxiety score ≥ 15), recent suicidal behavior (either preparatory acts/behavior, aborted attempt, interrupted attempt, or actual attempt in the past 3 months per the Screening Columbia Suicide Severity Rating Scale [C-SSRS], or active suicidal ideation with intent to act (defined as C-SSRS category score of 4 or 5 in the past month).
• Patients with (during Screening):
  • Severe hypertension (SBP > 180 mmHg and/or Diastolic Blood Pressure [DBP] > 110 mmHg), and patients with severe hypotension (SBP < 90 mmHg and/or DBP < 50 mmHg);
  • Hypertension or hypotension considered not controlled in line with clinical standards.
• Clinically significant electrolyte abnormality (e.g., hypokalemia, hypomagnesemia, or hypocalcemia) in the judgement of the Investigator.
• Current or prior history within the last 5 years of neoplasm (except for treated basal cell or squamous small cell carcinoma of the skin with no evidence of recurrence)
• Any concurrent clinically significant medical condition/disorder which in the Investigator’s opinion would interfere with the patient’s ability to comply with or complete the study or could affect the interpretation of the efficacy and safety variables.
• Use of any of the following medications or supplements within 30 days prior to Screening: 
  • Monoamine oxidase inhibitors (MAOIs);
  • Hydroxytryptophan (5-HTP) or L-tryptophan;
  • Telotristat ethyl.
• Patients currently taking one or more drugs known to prolong the QT interval and which are clearly associated with a known risk of Torsades de Pointe.
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2 at Screening as determined by central laboratory.
• 12-Lead electrocardiogram (ECG) results at Screening demonstrating QTcF interval > 450 ms for males or > 470 ms for females.
• Elevated alanine transaminase (ALT), aspartate transaminase (AST)), or total bilirubin (TBL) > 2 x upper limit of normal (ULN).
• Any ECG or clinical laboratory abnormality which precludes safe participation in the study in the opinion of the Investigator.
• History of active substance abuse disorder (including alcohol) within the past 2 years which, in the option of the Investigator, would limit the ability of the patient to provide adequate informed consent or to comply with study requirements.
• Use of any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to Screening, or 90 days if an investigational drug for PAH, unless local health authority guidelines mandate a longer period, or in consultation with the medical monitor, will not interfere with the safety or efficacy of the study.
• Any history of hypersensitivity to rodatristat ethyl, any of its components, or any components in the placebo preparation (refer to Rodatristat Ethyl IB, 2021).
• Patient is deprived of their liberty by a judicial or administrative decision, or is receiving psychiatric care, and is admitted to a health or social institution.
• Patient is subject to legal protection or is unable to express consent.

Eligibility last updated 5/9/22.  Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 11/23/22. Questions regarding updates should be directed to the study team contact.

• Male or female age ≥ 18 years.
• Prior diagnosis of multiple myeloma according to IMWG criteriaa , and measurable disease.
• Relapsed MM refractory to at least one IMiD, PI, and anti-CD38 antibody; patient does not need to be refractory to all three classes of treatment in the same LOT in order to be eligible.
  • Note: Refractory is defined as having progressive disease (PD) while on therapy or within 60 days following treatment.
  • Note: PD will be defined as one or more of the following based on the 2016 IMWG consensus criteria for response and minimal residual disease assessment in MM:
    • Increase of 25% from lowest confirmed response value in one or more of the following criteria:
    • Serum M-protein (absolute increase must be ≥ 0.5 g/dL);
    • Serum M-protein increase ≥ 1 g/dL, if the lowest M component was ≥ 5 g/dL;
    • Urine M-protein (absolute increase must be ≥ 200 mg/24 h);
    • In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be > 10 mg/dL);
    • In patients without measurable serum and urine M-protein levels and without measurable involved FLC levels, bone marrow plasma-cell percentage irrespective of baseline status (absolute increase must be ≥ 10%);
    • Appearance of a new lesion(s), ≥ 50% increase from nadir in the sum of the products of the maximal perpendicular diameters of measured lesions of > 1 lesion, or ≥ 50% increase in the longest diameter of a previous lesion > 1 cm in short axis; ≥ 50% increase in circulating plasma cells (minimum of 200 cells per µL) if this is the only measure of disease.
• Relapsed or refractory to last anti-MM regimen.
• ECOG performance status ≤ 2.
• Receiving subsequent treatment after becoming TCR (but not necessarily the first subsequent treatment), where initiation of this treatment will define the index date.
• Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
• * If application of International Myeloma Working Group (IMWG) criteria for diagnosis of MM or assessment of response is not available as part of regular clinical practice, clinician assessment may be used. The specific criteria used will be documented in the case report form.

• Diagnosis of current smoldering MM, active plasma cell leukemia, amyloidosis, and Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS) syndrome.
• Prior stem cell transplant within 12 weeks prior to study enrollment or active graft-versus-host-disease (GVHD).
• Any other active malignancy within 3 years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
• No investigational drug within 30 days or 5 half-lives preceding the index date, and throughout course of the study.
• Prior or concomitant treatment with an anti-BCMA bispecific antibody, including PF-06863135.
• Currently pregnant or breastfeeding.
  • Note: Additional inclusion/exclusion criteria may be applied in a sensitivity analysis to more closely match the Phase 2 MagnetisMM-3 (study C1071003) trial population depending on available data.
• The following information will be collected at the time of enrollment to the extent data are available. Laboratory measurements will be based on the most recent reading at the time of enrollment:
  • Left ventricular ejection fraction (LVEF) > 40% by a multigated acquisition (MUGA) scan or echocardiogram (ECHO);
  • Adequate hepatic function;
  • Total bilirubin < 2 x upper limit of normal (ULN) (< 3 x ULN if documented Gilbert’s syndrome);
  • Aspartate transaminase (AST) < 2.5 x ULN; and
  • Alanine aminotransferase (ALT) < 2.5 x ULN;
  • Adequate renal function;
  • Creatinine clearance > 30 mL/min (according to the Cockcroft Gault formula, by 24-hour urine collection for creatinine clearance, or according to local institutional standard method;
  • Adequate bone marrow function o Absolute neutrophil count (ANC) > 1.0 x 10^9 /L;
  • Platelets > 25 x 10^9 /L; and
  • Hemoglobin > 8 g/dL;
  • Resolved acute effects of any prior therapy to baseline severity or Common Terminology Criteria for Adverse Events (CTCAE) Grade < 1.
• History of impaired cardiovascular function or clinically significant cardiovascular diseases (CVD), defined as any of the following within 6 months prior to study enrollment:
  • Acute myocardial infarction (AMI) or acute coronary syndromes (e.g., unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, symptomatic pericardial effusion);
  • Clinically significant cardiac arrhythmias (e.g., uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
  • Thromboembolic or cerebrovascular events (e.g., transient ischemic attack, cerebrovascular accident, deep vein thrombosis [unless associated with a central venous access complication] or pulmonary embolism);
  • Prolonged QT syndrome (or triplicate average QTc corrected using Fridericia’s formula [QTcF] > 470 msec at screening);
  • Presence of ongoing Grade > 2 peripheral sensory or motor neuropathy;
  • History of any grade peripheral sensory or motor neuropathy, collected among patients with prior BCMA-directed therapy;
  • History of Guillain-Barré syndrome (GBS) or GBS variants, or history of any Grade > 3 peripheral motor polyneuropathy.
• Presence of surgical (including major surgery within 14 days prior to study enrollment), medical or psychiatric conditions including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the individual inappropriate for the study.
• Presence of active hepatitis B virus (HBV), hepatitis C virus (HCV), SARS-CoV-2, human immunodeficiency virus (HIV), or uncontrolled infection. Active infections must be resolved at least 14 days prior to study enrollment.
• Prior treatment with investigational drug within 30 days or 5 half-lives preceding the index date.

Eligibility last updated 2/14/22. Questions regarding updates should be directed to the study team contact.

• 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.

• Subject is greater than or equal to 18 years of age.
• Subject has history of persistent or long-standing persistent atrial fibrillation:
  • AF documentation requirement for persistent AF: Physician’s note indicating continuous AF > 7 days but no more than 1 year, and electrocardiographic documentation showing continuous AF within 90 days of the ablation procedure. Documentation can include a 24- hour holter (or equivalent) or two ECGs taken at least seven days apart within 90 days of the ablation procedure;
  • AF documentation requirement for longstanding persistent AF: physician’s note indicating at least 1 year of continuous AF, and electrocardiographic documentation showing continuous AF within 90 days of the ablation procedure. Documentation can include a 24- hour holter (or equivalent) or two ECGs taken at least seven days apart within 90 days of the ablation procedure. The performance of a successful cardioversion (sinus rhythm > 30 seconds) within 12 months of an ablation procedure with documented early recurrence of AF within 30 days should not alter the classification of AF as long-standing persistent.
• Stable Subject that is scheduled to undergo non-emergent cardiac surgical procedure(s) to be performed on cardiopulmonary bypass including open-heart surgery for one or more of the following: Mitral valve repair or replacement, Aortic valve repair or replacement, Tricuspid valve repair or replacement, Coronary artery bypass procedures, patent foramen ovale repair, and/or atrial septal defect.
• Left Ventricular Ejection Fraction ≥ 30% (determined by echocardiography or cardiac catheterization performed within 90 days of enrollment as documented in patient medical history).
• Subject is willing and able to provide written informed consent.
• Subject has a life expectancy of at least 5-years.
• Subject is willing and able to return for scheduled follow-up visits.

• Stand-alone AF without indication(s) for concomitant CABG and/or valve surgery.
• Previous surgical Maze procedure.
• Wolff-Parkinson-White syndrome or other Supra-Ventricular arrhythmia, AV nodal reentry.
• Prior cardiac surgery (Redo).
• Subjects requiring surgery other than CABG and/or cardiac valve surgery and/or patent foramen ovale repair, and/or atrial septal defect repair.
• Class IV NYHA heart failure symptoms.
• Prior history of cerebrovascular accident within 6 months or at any time if there is residual neurological deficit.
• Documented ST elevation MI within the 6 weeks prior to study enrollment.
• Need for emergent cardiac surgery (i.e., cardiogenic shock).
• Known carotid artery stenosis greater than 80%.
• Documented (continuous) AF duration of greater than ten years.
• LA diameter > 7 cm by TTE within 12 weeks (90 days) of procedure.
• Current diagnosis of active systemic infection.
• Severe peripheral arterial occlusive disease defined as claudication with minimal exertion.
• Renal failure requiring dialysis or hepatic failure.
• A known drug and/or alcohol addiction.
• Mental impairment or other conditions which may not allow the subject to understand the nature, significance and scope of the study.
• Pregnancy or desire to get pregnant within 12-months of the study treatment.
• Preoperative need for an intra-aortic balloon pump or intravenous inotropes.
• Requires anti-arrhythmic drug therapy for the treatment of a ventricular arrhythmia.
• Subjects who have been treated with thoracic radiation.
• Subjects in current chemotherapy.
• Subjects on long term treatment with oral or injected steroids (not including intermittent use of inhaled steroids for respiratory diseases).
• Subjects with known connective tissue disorders.
• Subjects with known hypertrophic obstructive cardiomyopathy.
• Subjects with known cold agglutinin.
• Patient has a condition that in the opinion of the investigator, may jeopardize the patient’s wellbeing and/or the soundness of this clinical study.
• Subject has a contraindication to post-operative anticoagulation; Patient has history of blood dyscrasia or clotting disorder (i.e., Idiopathic Thrombocytopenic Purpura [ITP] or Thrombotic Thrombocytopenic Purpura [TTP]).

Eligibility last updated 9/21/21. Questions regarding updates should be directed to the study team contact.

• 18 years of age and older.
• Patient is a good medical candidate for a standard of care or research biopsy or surgical procedure to obtain tissue.

• Individuals < 18 years of age.
• Uncontrolled concurrent illness including psychiatric illness, or situations that would limit compliance with the study requirements or the ability to willingly give written informed consent.
• Inaccessible tumor for biopsy or patient does not have tumor tissue available for research use.
• Biopsy must not be considered to be more than minimal risk to the patient.
• Have a contraindication to percutaneous biopsy including:
  • Significant coagulopathy that cannot be adequately corrected;
  • Severely compromised cardiopulmonary function or hemodynamic instability;
  • Lack of a safe pathway to the lesion per the interventional radiologist;
  • Inability of the patient to cooperate with, or to be positioned for, the procedure.

Eligibility last updated 8/23/21. Questions regarding updates should be directed to the study team contact.

• All patients ≥ 16 years old.
• Scheduled for a primary Hip Arthroscopy at Mayo Clinic (Rochester, MN), and Mayo Clinic Orthopedics and Sports Medicine (Minneapolis, MN). 

• Patients with a medical history of known allergies or intolerance to allergies or intolerance to Motrin, Gabapentin, Tylenol, dexamethasone, tramadol, or Robaxin.
• Substantial alcohol or drug abuse.
• History of narcotics within 6 months of surgery.
• Pregnancy.
• Renal impairment.
• Peptic ulcer disease.
• GI bleeding.

• All patients ≥ 16 years old.
• Scheduled for a primary Hip Arthroscopy at Mayo Clinic (Rochester, MN), and Mayo Clinic Orthopedics and Sports Medicine (Minneapolis, MN). 

• Patients with a medical history of known allergies or intolerance to allergies or intolerance to Motrin, Gabapentin, Tylenol, dexamethasone, tramadol, or Robaxin.
• Substantial alcohol or drug abuse.
• History of narcotics within 6 months of surgery.
• Pregnancy.
• Renal impairment.
• Peptic ulcer disease.
• GI bleeding.

Eligibility last updated 8/17/22. Questions regarding updates should be directed to the study team contact.

• Subjects who have received at least one dose of cilta-cel in a Janssen-sponsored clinical study.
• Subjects who have provided informed consent for Study MMY4002.

• No exclusion criteria are applicable in this study.

Eligibility last updated 11/2/21. Questions regarding updates should be directed to the study team contact.

• Patient must be ≥ 18 years of age.
• Patients must have confirmed diagnosis of AML (excluding acute promyelocytic leukemia) based on World Health Organization classification (Arber 2016).
• Disease characteristics and allowable prior therapy:
  • Patients must be evaluated for any available standard of care therapies (including induction, consolidation chemotherapy and/or transplant) and, in the opinion of the treating physician, be deemed appropriate for this experimental therapy;
  • Treatment-naïve (untreated) patients will be allowed in the Expansion Phase for Regimen C (Triplet) (IMGN632 + azacitidine + venetoclax). No prior treatments with hypomethylating agents (HMAs) for MDS are allowed;
  • Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry [IHC]);
  • Patients may have received prior CD123-targeted therapies, except IMGN632, as long as CD123 remains detectable during screening;
  • Relapsed or refractory CD123-positive AML patients will be allowed to enroll in the Escalation Phase of Regimens A, B, and C (Triplet) (IMGN632 + azacitidine, venetoclax, or azacitidine + venetoclax, respectively) and relapsed CD123-positive AML patients will be allowed to enroll the Expansion Phase of Regimens A-C;
  • Note: Patients may also have received up to 2 prior lines of therapy; e.g., frontline treatment (induction, consolidation [including transplant], and maintenance) and 1 salvage regimen;
  • Patients enrolling in Regimen D must be in CR (CR/CRh/CRp/CRi) and be MRD+ at the time of screening, confirmed by central laboratory testing. Patients may have no more than 2 prior lines of therapy (which may include stem cell transplant); i.e., frontline or first salvage.
  • Note: Fit patients who received intensive treatment (e.g., 3+7, HiDAC, etc.) are eligible for Regimen D Cohort D1. Unfit patients who received non-intensive treatment (e.g., HMA, low dose cytarabine, etc.) are eligible for Regimen D Cohort D2.
• Eastern Cooperative Oncology Group performance status ≤ 1. If non ambulatory due to a chronic disability, must be Karnofsky performance status ≥ 70.
• Previous treatment-related toxicities must have resolved to Grade 1 or baseline (excluding alopecia).
• Total white blood cell count must be less than 25 × 10^9 cells/L. Hydroxyurea may be used to control blood counts before Cycle 1 Day 1, at the discretion of the treating physician, according to institutional practice. During the Escalation Phase in Regimens A-C, hydroxyurea may also be used during Cycle 1.
• Liver enzymes (AST and ALT) ≤ 3 × the upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 × the ULN.
• An estimated glomerular filtration rate (eGFR) of > 30 mL/min/1.73 m^2 or creatinine clearance of > 30 mL/min.
• Left ventricular ejection fraction (LVEF) ≥ 45% based on locally available assessment, eg, echocardiogram or other modality.
• Patients with prior autologous or allogeneic bone marrow transplant are eligible. Patients with an allogeneic transplant must meet the following conditions: The transplant must have been performed more than 120 days before the date of dosing on this study, the patient must not have active ≥ Grade 2 graft versus host disease (GvHD), or extensive chronic GvHD of any severity, and must be off all immunosuppression for at least 2 weeks prior to first dose of IMGN632.
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
• Women of childbearing potential (WCBP), defined as sexually mature women who have not undergone surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who have had menses any time in the preceding 12 consecutive months), must agree to use acceptable contraceptive methods while on study drug and for at least 7 months after the last dose of IMGN632.
• WCBP must have a negative pregnancy test within 3 days before the first dose of study drug.
• Male patients who are able to father children must agree to use acceptable methods of contraception throughout the study and for at least 4 months after the last dose of IMGN632.
• Patients with prior malignancy are eligible; however, the patient must be in remission from the prior malignancy and have completed all systemic chemotherapy and radiotherapy for the prior malignancy at least 6 months before enrollment, and all treatment-related toxicities must have resolved to Grade 1 or less.
• Note: patients with prostate cancer or breast cancer on adjuvant hormonal therapy are eligible.
• Note: patients with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible.

• Patients who have received any anticancer therapy, including investigational agents, within 14 days (or within 28 days for checkpoint inhibitors) before drug administration on this study (hydroxyurea is allowed before beginning study treatment). Patients must have recovered to baseline from all acute toxicity from this prior therapy.
• Patients who have been previously treated with IMGN632. Patients with myeloproliferative neoplasm-related secondary AML are excluded from the Dose Expansion Phase of the study.
• Patients with active central nervous system (CNS) AML will be excluded. A lumbar puncture does not need to be performed unless there is clinical suspicion of CNS involvement per investigator judgement. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS AML is allowed with the approval of the sponsor.
• Patients with a history of sinusoidal obstruction syndrome/venous occlusive disease of the liver.
• Myocardial infarction within 6 months before enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities before study entry.
• Clinically relevant active infection including known active hepatitis B or C, HIV infection, or cytomegalovirus or any other known concurrent infectious disease that, in the judgment of the investigator, would make a patient inappropriate for enrollment into this study (testing not required).
• Patients who have undergone a major surgery within 4 weeks (or longer if not fully recovered) before study enrollment.
• Serious or poorly controlled medical conditions that could be exacerbated by treatment or that would seriously compromise safety assessment or compliance with the protocol, in the judgment of the investigator.
• Women who are pregnant or breastfeeding.
• Prior known hypersensitivity reactions to monoclonal antibodies (≥ Grade 3).
• Prior known hypersensitivity reactions to study drugs and/or any of their excipients.
• Patients who have a history of allergy to IMGN632 (or any of its excipients), azacitidine, or venetoclax.

Eligibility last updated 11/28/22. Questions regarding updates should be directed to the study team contact. 

• Female patient with a diagnosis of Ulcerative Colitis (UC) or Crohn’s Disease (CD) seen in the IBD clinic in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester.
• Who are between 18-64 years of age.
• Ability to provide informed consent.
• Ability to complete all aspects of this trial.

• Female patients with a diagnosis of UC or CD with medical co-morbidity or factor judged by the investigator to preclude participation in the study or which might hinder adherence.
• Participation in another organized wellness program.

• Patients who are 10 to 45 years old and of both sexes.
• Patients with a diagnosis of OCD of the capitellum ICRS Grades 3 or 4 via standard-of-care X-ray CT or MRI, irrespective of the size or location of the lesion.
• Patients who are scheduled to undergo surgery for the treatment of the OCD lesion, irrespective of the procedure.

• Patients with other current or prior elbow pathology.
• Patients with prior history of elbow surgery.
• Patients who do not consent to participate.

Eligibility last updated 9/3/21. Questions regarding updates should be directed to the study team contact.

• Adult and pediatric patients.
• Undergoing surgical resection of their brain AVM.
• Have not undergone previous stereotactic radiosurgery or endovascular embolization.  

• Have undergone previous stereotactic radiosurgery or endovascular embolization.

Eligibility last updated 9/7/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 2/21/23. Questions regarding updates should be directed to the study team contact.

• Male or female patients aged ≥ 18 years.
• A diagnosis of CD with minimum disease duration of 6 months with involvement of the ileum and/or colon documented on colonoscopy
• Have an endoscopically-confirmed active Crohn's disease with active disease defined by SES-CD > 6 (>4 if ileal only), AND active symptoms of Crohn's disease (CDAI score >220) 
• Homozygous for CARD9 SN12 risk allele, without the protective exon 11 polymorphism
• Subjects receiving oral aminosalicylates (at a stable dose for 2 weeks prior to baseline), immunomodulators (at a stable dose for 4 weeks prior to baseline), anti-TNF, anti IL12/23, or anti-integrin therapy (at stable maintenance doses for > 8 weeks) may continue their use during the study.
• Subjects receiving oral corticosteroids may continue their use during the study provided the dose (prednisone up to 20 mg/day, budesonide up to 9 mg/day) has been stable for two weeks prior to screening.
• Have had age-appropriate and disease-duration-appropriate colon cancer screening1 without unresected dysplasia.
• Women of childbearing age, excluding those with prior bilateral tubal ligation or at least one-year post-menopause, must not be pregnant, lactating, or planning to become pregnant. They must agree to use effective contraception throughout the study period.
• Subjects must be able to provide informed consent and understand, agree with, and be able to adhere to daily diary entries, all scheduled visits, tests, procedures, and protocol in English.

• Known hypersensitivity or allergy to posaconazole or other azole antifungal agents
• Concomitant medications primarily metabolized by CY3PA4 including:
  • HMG-CoA inhibitors primarily metabolized by CY3PA4 (increases risk of rhabdomyolysis);
  • Sirolimus;
  • Ergot alkaloids;
  • Vincristine.
• Proarrhythmic conditions.
• Moderate or severe renal impairment (Cr Clearance < 50).
• Current diagnosis of ulcerative colitis, indeterminate colitis, ischemic colitis, infectious colitis, or microscopic colitis.
• Fulminant colitis, toxic megacolon, peritonitis, ileostomy or colostomy.
• Stool sample positive for pathogens including ova and parasites, Salmonella, Shigella, and C. difficile at screening.
• History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease or any other medical condition that, in the Investigators opinion, would prevent the subject from participation in the study.
• Treatment with antibiotics, antifungal agents, probiotics, or prebiotics within two weeks of screening.
• Alcohol or drug abuse (in the opinion of the Investigator) that would interfere with compliance.
• Any other investigational therapy or treatment within four weeks of screening.

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.

Eligibility last updated 8/9/22. Questions regarding updates should be directed to the study team contact.