Eligibility last updated 2/20/23. 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.

• Patient must be aged ≥ 18 years at the time of signing the informed consent.  In some countries, parental consent may be required in addition to an assent form for patients who are 18 years of age.
• Patient must have histologically documented diagnosis of B-cell non-Hodgkin lymphoma (B-NHL) as defined by a B-cell neoplasm in the World Health Organisation classification scheme except as noted in the exclusion criteria.
• Patient has relapsed after or failed to respond to at least 2 but no more than 5 prior systemic treatment regimens (including investigational therapy) and for whom there is no available therapy expected to improve survival (e.g., standard chemotherapy, autologous stem cell transplantation (SCT), chimeric antigen receptor T cell (CAR-T) cell therapy).
• Documented active disease requiring treatment that is relapsed or refractory defined as: -Recurrence/relapse of disease after response to prior line(s) of therapy.
• Progressive disease (refractory) on/after completion of the treatment regimen preceding entry into the study.
• Must have at least one measurable, fluorodeoxyglucose positron emission tomography (FDG-PET) avid lesion (except for MZL), based on bi-dimensional assessment on PET and computed tomography (CT)/magnetic resonance imaging (MRI) scan. A measurable lesion is defined as:
  • For nodal lesions: longest diameter > 1.5 cm;
  • For extranodal lesions: longest diameter > 1 cm;
  • Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2. Performance status must not have deteriorated by ≥ 2 levels within 2 weeks after providing informed consent.
• Adequate haematologic, hepatic, and renal function.
• Adequate cardiac function as demonstrated by left ventricular ejection fraction > 50% on screening cardiac multigated acquisition, magnetic resonance imaging, or echocardiogram.
• Women of childbearing potential and men should use protocol defined contraceptive measures.
• Willing and able to participate in all required study evaluations and procedures including receiving IV administration of study intervention and admission to the hospital, when required, for administration of study treatment and monitoring.
• All patients must be willing to undergo an incisional or excisional lymph node or tissue biopsy or to provide a lymph node or tissue biopsy from the most recent available archival tissue.
• For inclusion in the genetic component of the study, patients must fulfil protocol defined criteria.

Inclusion Criteria
•Module 1 Additional Inclusion Criteria for Cohort B1 (R/R mantle cell lymphoma [MCL]):

• Histologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1, as assessed by Investigator or local pathologist.
• Must have relapsed after or failed to respond to at least 2 prior lines of treatment, including one anti-CD20 monoclonal antibody (mAb) and a Bruton's tyrosine kinase inhibitor.

Additional Inclusion Criteria for Cohort B2 (R/R FL or MZL):

• Histologically confirmed diagnosis of FL Grade 1, 2, or 3a OR histologically confirmed MZL including splenic, nodal, and extranodal subtypes, as assessed by Investigator or local pathologist.
• For FL patients: Previously received at least 2 prior systemic treatment regimens (including anti-CD20 mAb and an alkylating agent).
• For MZL patients: Previously received at least 2 prior lines of systemic therapy including at least one anti-CD20 mAb-directed regimen either as monotherapy or as chemoimmunotherapy (Helicobacter pylori eradication and radiation therapy alone will not be considered a systemic treatment regimen).

Additional Inclusion Criteria for Cohort B3 (R/R DLBCL):

• Histologically confirmed DLBCL (including transformed FL) OR FL Grade 3b.
• Must have received 2 lines of systemic therapy including at least one anti-CD20 mAb-directed regimen and must have failed or are ineligible for stem cell transplantation (if indicated per local institutional guidelines).

• Diagnosis of post-transplant lymphoproliferative disease, Richter's transformation, Burkitt's lymphoma, Burkitt-like lymphoma, lymphoblastic lymphoma/leukaemia, chronic lymphocytic leukaemia, small lymphocytic lymphoma.
• High risk of TLS according to Howard modification of Cairo-Bishop criteria and/or the presence of bulky disease.
• Unresolved toxicity from prior anticancer therapy. Patients with Grade 2 neuropathy or Grade 2 alopecia are eligible.
• Active idiopathic thrombocytopenic purpura.
• Active central nervous system (CNS) involvement by lymphoma, leptomeningeal disease or spinal cord compression.
• Known history of infection with human immunodeficiency virus.
• Known serologic status reflecting active hepatitis B or C infection; concurrent infection with cytomegalovirus (CMV).
• Patients must be tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and those with active infection in accordance with local testing guidelines will be excluded. -Any evidence of severe or uncontrolled systemic diseases; current unstable or uncompensated respiratory or cardiac conditions; uncontrolled hypertension; history of, or active, bleeding diatheses; uncontrolled active systemic fungal, bacterial, or other infection.
• Any of the following cardiac criteria at screening: patients with a history of myocarditis within one year of study entry, or heart failure; mean resting corrected QT interval (QTcF) ≥ 470 msec obtained from 3 electrocardiograms (ECGs), in the absence of a cardiac pacemaker; any factors that increase the risk of QTc prolongation or risk of arrhythmic events; any clinically important abnormalities in rhythm, conduction or morphology of resting ECG.
• History of another life-threatening malignancy ≤ 2 years prior to first dose of study intervention.
• Any of the following currently or in the 6 months prior to the first dose of study intervention: coronary artery bypass graft; angioplasty; vascular stent; myocardial infarction; angina pectoris; haemorrhagic or thrombotic stroke, including transient ischaemic attacks or any other CNS bleeding.
• Treatment with any of the following:
  • radiotherapy less than 2 weeks prior to the first dose of study intervention; any investigational agents or study drugs from a previous clinical study within ≤ 14 days or 5 half-lives prior to the first dose of study intervention; any other chemotherapy, immunotherapy, immunosuppressant medication or anticancer agents within 21 days of the first dose of study intervention;
  • prior allogenic haematopoietic stem cell transplantation (HSCT) within 6 months from the first dose of study intervention (patients > 6 months after allogenic HSCT are eligible in the absence of active graft-versus host disease and concomitant immune-suppressive therapy). Eligible patients must have stopped immunosuppression at least 2 months prior to study entry; prior cellular therapies such as CAR-T and/or autologous HSCT within 3 months prior to the first dose of study intervention; major surgery ≤ 21 days, or minor surgical procedures ≤ 7 days, prior to the first dose of study intervention; prescription or non-prescription drugs or other products known to be sensitive substrates of BCRP, OCT2, OAT3, OATP1B1, OATP1B3, CYP2B6, CYP2C8, CYP2C9 or CYP2D6, or reversible moderate or strong cytochrome 3A (CYP3A) inhibitors, which cannot be discontinued within 5 half-lives of the first dose of study intervention and withheld throughout the study until 14 days after the last dose of AZD0466; moderate or strong mechanism-based inhibitors or inducers of CYP3A4 which cannot be discontinued within 5 half-lives plus 12 days of the drug prior to the first dose of study intervention and withheld until 14 days after the last dose of AZD0466; concurrent anticoagulation therapy, including aspirin, which cannot be stopped; medications with known risk of Torsades de Pointes within 5 half-lives of the first dose of study intervention and continuing until 5 half-lives after the last dose of AZD0466.
• Administration of a live, attenuated vaccine within 4 weeks before first dose of study intervention.
• Administration of inactivated vaccines or protein/RNA immunogen vaccines.
• Patients with a known hypersensitivity to polyethylene glycol, pegylated products, or drugs with a similar chemical structure or class to AZD0466 or other BH3 mimetic.

Exclusion Criteria- Module 1 Additional Exclusion Criteria for Cohort B1:

• Patients with known blastoid or pleiomorphic variant at study entry/most recent relapse.

Additional Exclusion Criteria for Cohort B2:

• Histologically confirmed diagnosis of FL grade 3B.
• Known transformation to aggressive lymphoma; e.g., large cell lymphoma.

Eligibility last updated 2/8/22. Questions regarding updates should be directed to the study team contact.

• Must be employed as a Mayo Clinic Physician.

• Any physical condition that might prevent them from sitting for 20-30 minutes in the MindBreaks room.
• Significant hearing loss that they would not be able to hear the audio stimuli.
• Significant vision loss that they would not be able to see the visual stimuli.
• No children will be recruited.
• Unable to consistently use the MindBreaks room on at least a weekly basis during the course of the study.

• Patients ≥ 18 years of age with Hepatocellular Carcinoma (HCC) and SEA American self-report (they or their family members are from/had been from Cambodia, Laos, or Vietnam) are eligible.
• Diagnosis of HCC.

• < 18 years of age. 

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

Eligibility last updated 9/23/22. Questions regarding updates should be directed to the study team contact.

• Adult males and females over the age of 18.
• Subjects living at Acacia Creek Retirement Community who use a Sleep Number® bed.

• Individuals under the age of 18.
• Subjects who do not have a Sleep Number® bed.
• Subjects without an internet connection to transmit nightly SleepIQ® data.

Eligibility last updated 1/31/22. Questions regarding updates should be directed to the study team contact.

• Patients who provide informed consent to participate in the study.
• Subjects: 18 years and older.
• Scheduled to undergo surgery resulting in a complex recovery as evaluated by the treating Department of Surgery surgeon.  This includes, but is not limited to, the following inpatient elective surgery procedures:
  • esophagectomy;
  • pancreatectomy;
  • pancreatectomy;
  • major liver resections;
  • open vascular surgery.
• Subjects are committed to daily exercise as outlined in the protocol.

• < 18 years of age.
• Subject is pregnant.
• Subject is dismissed from the hospital to a nursing home or long term care facility.
• Subject cannot commitment to daily exercise as outlined in the protocol.
• Subjects enrolled in another device or drug study does not necessarily preclude them from participating in this study.  Please check with the PI for inclusion if the subject is on another device or drug study.
• Subject does not have wifi access at home.
• Subject does not have a smartphone in which they can download the app for the watch device data to be downloaded.

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

• All adult patients ≥ 18 years of age.
• Undergoing spinal fusion surgery in which the facet articular cartilage or disc and endplate cartilage is removed and discarded to allow for spinal fusion. Cervical, thoracic, and lumbar.

• < 18 years of age. 

Eligibility last updated 9/19/22. Questions regarding updates should be directed to the study team contact.

• Adult patients with a diagnosis of bilateral moderate-to-profound sensorineural hearing loss who are undergoing unilateral or simultaneous bilateral cochlear implantation at the Mayo Clinic in Rochester MN.

• Patients undergoing revision implantation, completion bilateral cochlear implantation, or implantation for unilateral deafness will be excluded from enrollment.
• Patients unable or unwilling to use a computer or similar device will be excluded from enrollment.
• Patients will be excluded if they speak a language not supported by the Sound Success platform.

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

Eligibility last updated 9/30/22. Questions regarding updates should be directed to the study team contact.

• Males or females 18 years of age or older.
• Meet the requirements for one of the case or control groups.
• MS patients undergoing neurologic evaluation procedures as part of Understanding Sex Differences in Multiple Sclerosis Spectrum of Demyelinating Disorders (IRB# 19-002807) Study or the Mayo Clinic Neurology Multiple Sclerosis Clinic
• Control group (n=100) without inflammatory-demyelinating diseases of the central nervous system (Control group (n=100) will have no MS or related disorder diagnosis).
• Capacity to sign consent

• Participants unable to lie down without moving for 20 minutes.
• Women who are pregnant or cannot stop breast feeding for 24 hours.
• For all patients and controls, any acute glucocorticoid (e.g. IV methylprednisolone or PO prednisolone) use within 2 weeks is an exclusion to limit medication interaction but preserve possible chronic systemic inflammation interaction with microglia activation metrics. Chronic disease modifying treatments in MS are allowed as these medications are not known to impact microglia activation.
• Standard safety exclusionary criteria for MRI such as metallic foreign bodies, pacemaker, etc., since the quantitative PET data analysis is based on anatomic criteria that are established uniquely for each subject by registration to his/her MRI.

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

Eligibility last updated 9/27/23. Questions regarding updates should be directed to the study team contact.

- CHA2DS2-VASc ≥ 4 with age ≥ 65;
- CHA2DS2-VASc ≥ 4 with significant left atrium enlargement or elevated NT-proBNP;
- CHA2DS2-VASc = 3 with age ≥ 75
- CHA2DS2-VASc = 3 with significant left atrium enlargement or elevated NT-proBNP
- CHA2DS2-VASc score = 2 with age ≥ 65 and significant left atrium enlargement or
elevated NT-proBNP.

- Anytime in the past; and
- Documented by an electrocardiographic recording; and
- Episode lasting 6 minutes or longer1*.

- Prior procedure involving opening the pericardium or entering the pericardial space.
- Prior LAA occlusion, exclusion, or removal (surgical or percutaneous).
- Planned cardiac surgical procedure using non-sternotomy approaches.
o Partial sternotomies will be allowed.
- Patients whose planned procedure is a heart transplant or implantation of any
ventricular assist devices.
- Active endocarditis.
- Active systemic infection at the time of cardiac surgery requiring antibiotics,
including known SARS-CoV2 infections regardless of symptoms.
- Known allergy to Nitinol or nickel sensitivity.
- Known medical condition with expected survival of less than 1 year.
- Other comorbidities that in the investigator's opinion make the subject unsuitable
candidate to complete the protocol required visits.
- Current enrollment in an investigation or trial or an investigational devices or
investigational drug that would interfere with this trial.
- Mental impairment or other psychiatric conditions which may not allow the patient to
understand the nature, significance, and scope of the trial.
- Pregnancy.
- Known severe symptomatic carotid disease.

• 18–65 years of age.
• Ability to provide written informed consent..
• Confirmed diagnosed with UC by colonoscopy and histology and suffering from mild to moderate UC as defined by MMDAI with score of 3-9.
• On a stable dose of aminosalicylate (i.e., no change in medication within 4 weeks of study enrollment) and not planning to initiate new medication other than the study drug.
• Fecal calprotectin level > 100 mg/g.
• For women of childbearing potential or men with a partner of childbearing potential, agree to use birth control methods during the study and at least 30 days after dosing (per FDA guidelines).
• For the expansion cohort, a flexible sigmoidoscopy is required, unless an endoscopy completed within 3 months from enrollment is available.

• Pregnancy, planned pregnancy, breastfeeding women.
• Evidence of severe UC disease (MMDAI score greater than or equal to 10).
• Evidence of any active or recent infection including chronic infectious disease such as chronic chest infection with bronchiectasis or sinusitis, or covid-19 infection in the past 3 months.
• Treatment with immunosuppressants or anti-cancer drugs; e.g., anti-TNF-α agents, anti-integrin agents, azathioprine or 6-MP, 6-thioguanine, methotrexate, ozanimod, tofacitinid, upadacitinib, tacrolimus, cyclophosphamide, or cyclosporine or any other therapy that is not an aminosalicylate within the last 3 months.
• Received an investigational drug within 3 months (or 5 half-lives, whichever is longer) before study entry.
• Use of steroidal drugs to treat UC (e.g., prednisone > 20 mg/day).
• Use of probiotics within the last 1 month.
• Treatment with systemic broad-spectrum antibiotics in the past 3 months.
• Major active systemic autoimmune disease other than UC.
• History of anaphylaxis or allergies to probiotics.
• History of alcohol or drug abuse within the past 2 years.
• History of stroke, or any cerebrovascular disease requiring medication/treatment.
• History of cancer, apart from successfully treated basal cell carcinoma or in situ carcinoma of the cervix >1 year prior to enrollment.
• Significant laboratory abnormalities, including liver transaminases (AST or ALT) > 1.5 X the upper limit of normal.
• Second degree higher heart block or clinically significant arrythmia.
• Any other clinically significant renal, hepatic, hematological or other disease or laboratory abnormality which, in the opinion of the investigator, would interfere with the conduct, the interpretation of the safety signals or results of the trial, or would place the subject at unacceptable risk.

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

Eligibility last updated  10/31/22. Questions regarding updates should be directed to the study team contact.

• Between 18 and 85 years of age (inclusive) at the initial screening visit.
• Meets 2011 consensus criteria for svPPA (Gorno-Tempini et al. 2011).
• MRI at screening is consistent with the underlying svPPA with no large strokes or severe white matter disease (Fazekas Grade ≤ 2; Fazekas et al. 1987);
• CDR® plus NACC FTLD (Miyagawa et al. 2020) global score at screening ≤1.
• The following medications are allowed, but must be stable for 2 months prior to the initial screening visit:
  • Food and Drug Administration (FDA)-approved Alzheimer's disease (AD) medications;
  • FDA-approved psychotropic medications;
  • Other medications (except those listed under exclusion criteria) are allowed as long as the dose is stable for 30 days prior to the initial screening visit.
• Has a reliable study partner who agrees to accompany the participant to visits, and spends at least 5 hours per week with the participant.
• Agrees to 2 LPs.
• Signed and dated written informed consent obtained from the participant and the participant's study partner in accordance with local Institutional Review Board (IRB) regulations.
• WOCBP must agree to abstain from sex or use highly effective birth control that includes two methods of contraception (one of which must be a barrier method) for the duration of the screening period, the RDBPC treatment period, and for 30 days after the last dose of study drug (active or placebo).
• Males must agree to abstain from sex with WOCBP or use an adequate method of contraception for the duration of the RDBPC treatment period and for 90 days after the last dose of study drug (active or placebo).
• Able to swallow pills whole without crushing or chewing.

• A clinical diagnosis of probable AD (McKhann et al. 2011) or previous biomarker evidence of AD biology using amyloid positron emission tomography (PET) imaging, CSF amyloid beta (A?)/total tau (t-tau) ratio, CSF/plasma amyloid beta isoform with 40 amino acid residues (Aβ40)/amyloid beta isoform with 42 amino acid residues (Aβ42) ratio, or plasma phosphorylated tau [phosphorylated tau at residue 181 (p-tau181) and phosphorylated tau at residue 217 (p-tau217)] assessments.
• A clinical diagnosis of a comorbid FTLD-associated clinical syndrome other than svPPA, including:
  • logopenic primary progressive aphasia (lvPPA; Gorno-Tempini et al. 2011);
  • non-fluent/agrammatic variant primary progressive aphasia (nfvPPA; Gorno-Tempini et al. 2011);
  • behavioral variant for frontotemporal dementia (bvFTD; Rascovsky et al. 2011). Patients who meet diagnostic criteria for svPPA (Gorno-Tempini et al. 2011) may still be included if they have a secondary diagnosis of bvFTD, so long as the PI can reasonably attribute their disinhibition, dietary changes, compulsions, and/or loss of empathy to anterior temporal lobe atrophy (Seeley et al. 2005) and MRI is consistent with right anterior atrophy (or left temporal atrophy in participants with suspected right hemispheric language dominance);
  • progressive supranuclear palsy (PSP; Höglinger et al. 2017); e. corticobasal syndrome (CBS; Armstrong et al. 2013).
• Any other medical condition other than FTLD that is likely to account for cognitive or behavioral deficits (e.g., uncontrolled seizure disorder, stroke, vascular dementia, substance abuse or alcoholism, Lewy body disease).
• History of uncontrolled thyroid disease or evidence thereof [i.e., abnormal free thyroxine (T4) levels and thyroid stimulating hormone (TSH) > 10 milli-international units (mIU)/liter (L) at screening (confirmed by repeat)].
• Serious autoimmune disease, or ongoing immunocompromised state.
• History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof at screening).
• History or presence of gastrointestinal (GI) or other disease known to interfere with absorption, distribution, metabolism, or excretion of drugs, or a history of surgery known to interfere with absorption or excretion of drugs (i.e., gastric bypass).
• Within 1 year prior to initial screening visit or between screening and baseline (pre-dose Day 1), any of the following: myocardial infarction; hospitalization for congestive heart failure; hospitalization for, or symptoms of, unstable angina; or syncope.
• History of major psychiatric illness or untreated depression that in the opinion of the PI would pose a safety risk or interfere with the appropriate interpretation of study data.
• Neutrophil count <1,500/cubic millimeter (mm3), platelets <100,000/mm3, serum creatinine >1.5 x upper limit of normal (ULN), total bilirubin (TBL) >1.5 x ULN, alanine aminotransferase (ALT) >1.5 x ULN, aspartate aminotransferase (AST) >1.5 x ULN, or international normalized ratio (INR) >1.2 at screening (confirmed by repeat).
• Evidence of any clinically significant findings on screening or baseline evaluations which, in the opinion of the PI would pose a safety risk or interfere with appropriate interpretation of study data.
• Corrected QT interval by Fridericia (QTcF) ≥ 470 milliseconds (msec) or uncontrolled arrhythmia or frequent premature ventricular contractions (PVCs; >5/minute) or Mobitz Type II second or third degree atrioventricular (AV) block or left bundle branch block or right bundle branch block with a QRS duration ≥ 150 msec or intraventricular conduction defect with a QRS duration ≥ 150 msec or evidence of acute or sub-acute myocardial infarction or ischemia or other ECG findings at screening or baseline that, in the PI's opinion, would preclude participation in the study.
• Pathologic renal findings at screening as defined by the presence of either of the following criteria:
  • Estimated glomerular filtration rate (eGFR) [determined by the Modification of Diet in Renal Disease (MDRD) Study equation] < 30 milliliter (mL)/minute/1.73 square meter (m^2). The MDRD Study equation is as follows: eGFR (mL/minute/1.73 m^2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American), where Scr = serum creatinine in mg/deciliter (dL) as measured by a method calibrated to an isotope dilution mass spectrometry (IDMS) reference method;
  • Serum creatinine ≥ 2.5 mg/dL;
  • Hemoglobin A1C > 7.5% at screening (confirmed by repeat);
• Current or recent history (within four weeks prior to initial screening visit) of a clinically significant bacterial, fungal, or mycobacterial infection.
• Current clinically significant viral infection, including "known" positive status for human immunodeficiency virus (HIV) (i.e., based on prior testing; HIV testing will not be performed as part of the screening evaluations for this trial).
• Major surgery within four weeks prior to initial screening visit.
• Blood transfusion within 4 weeks of initial screening visit.
• History of stem cell treatment.
• Any contraindication for MRI or unable to tolerate MRI at screening.
• Any contraindication to or unable to tolerate LP at screening, including the use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to the initial screening visit.
• Participants who, in the opinion of the PI, are unable or unlikely to comply with the dosing schedule or study evaluations.
• Prior treatment with verdiperstat.
• Treatment with another investigational drug within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with investigational drugs other than verdiperstat while on study will not be allowed.
• Treatment with systemic corticosteroids or steroid sparing systemic immunosuppressive agents within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with systemic corticosteroids or other systemic immunosuppressive therapy while on study will not be allowed.
• Treatment with strong inhibitors of CYP1A2 (i.e., ciprofloxacin, enoxacin, fluvoxamine) within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with strong inhibitors of CYP1A2 while on study will not be allowed.
• Known hypersensitivity to the inactive ingredients in the study drug products (active or placebo).
• Known to be pregnant or lactating, or positive pregnancy test at screening or baseline (pre-dose Day 1).
• Cancer within 5 years of initial screening visit, except for basal cell carcinoma.
• History or evidence at screening of known disease-associated mutations associated with FTLD without trans-activation response deoxyribonucleic acid-binding protein of 43 kilodaltons (TDP-43) inclusions [e.g., mutations in the genes encoding chromatin-modifying protein/charged multivesicular body protein B2 (CHMPB2), microtubule-associated protein tau (MAPT), or fused in sarcoma (FUS)].

Eligibility last updated 3/7/23. Questions regarding updates should be directed to the study team contact.

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

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

• Subjects ≥ 18 years age who will undergo clinically indicated stress or non-stress cardiac MRI (CMR) imaging with contrast on a GE scanner in Rochester, MN.

• Patients who would fall outside of the range for normal operating mode. Examples include patients with retained implantable electronic device leads, or those with a legacy device requiring active monitoring by a physicist (with limitation of the whole-body specific absorption rate ‘SAR’ exposure to less than 2W/kg), and patients with a cardiac implantable electronic device (CIED).

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.

Key

• ≥ 18 years or age.
• Undergoing open cubital tunnel release at the level of their elbow will be selected to collect muscle biopsies of their biceps muscle.

• Previous history of peripheral nerve injury involving the musculocutaneous nerve.
• Previous history of surgery at the level of the arm (fractures around the shoulder or elbow).
• Medical history of neurological diseases.

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

Eligibility last updated 11/29/22. Questions regarding updates should be directed to the study team contact.

- Ability to provide written informed consent prior to initiation of any trial-specific procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.

- Biological male subjects who do not agree to avoid donation of sperm from the time of consent through the end of the subject’s participation in the trial and an additional 90 days thereafter.

- Nephrotic syndrome.

- Serum IgG < 600 mg/dL at screening.

- Chronic systemic immunosuppression, including glucocorticoids, within 16 weeks of randomization.

- Participation in another interventional clinical trial and receipt of another investigational drug within 30 days prior to the administration of IMP or 5 half-lives from last investigational drug administration, whichever is longer.

- Chronic infectious disease, or acute infectious disease at time of screening.

- Type 1 diabetes, or poorly controlled Type 2 diabetes.

- Uncontrolled hypertension.

- Subject has kidney biopsy with a MEST or MEST-C score of T2 or C2 from the Oxford IgAN classification schema. If MEST-scoring was not performed, the presence of > 50% tubulo-interstitial fibrosis, or crescents in > 25% of glomeruli is exclusionary.

Note: this criterion does not apply to the exploratory cohort.

Note: The most recent kidney biopsy will take precedence for purposes of eligibility.

- History of a previous hypersensitivity or severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis to any of the ingredients of the sibeprenlimab SC injection formulation.

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

Eligibility last updated 1/8/24. Questions regarding updates should be directed to the study team contact.

• Signed Informed Consent Form).
• Age 18–70 years at time of signing Informed Consent Form.
• Body mass index (BMI) of 18 to 35 (kg/m2 ) at screening.
• Ability to comply with the study protocol, in the investigator’s judgment.
• History of medically diagnosed celiac disease that meets at least one of the following three criteria: ­
  • Any change in duodenal villous architecture consistent with celiac disease (e.g., atrophy, blunting, flattening or effacing of villi) and positive celiac serology (must have both);
  • Increased intraepithelial lymphocytes (IEL), positive celiac serology and symptoms or signs responsive to GFD (must have all three). In the context of positive celiac serology, symptoms or signs responsive to GFD, and a positive HLA-DQ2.5 genotype, a duodenal biopsy that shows IELs alone (without change in villous architecture) is sufficient histologic support of the diagnosis of celiac disease;
  • tTG-IgA > 10x ULN, have had a positive celiac serology (i.e., DGP-IgG, DGP-IgA or EMA (endomysial antibody)-IgA) on a separate blood sample, and symptoms or signs responsive to GFD (must have all three).
• Be on a GFD for at least 12 months prior to screening.
• Willing and able to use the electronic patient-reported outcome (ePRO) device.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two effective methods of contraception, including at least one method with a failure rate of < 1% per year during the treatment period and for at least 5 half-lives of DONQ52 after the last dose of study drug, and agreement to refrain from donating eggs for the same period. ­ A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). ­ Examples of highly effective contraceptive methods with a failure rate of < 1% per year include; bilateral tubal ligation, male partner sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. ­ A barrier method may be used as the second contraceptive method.  The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception.
• Valid results from either central testing or previous testing of blood documenting positive for the HLA-DQ2.5 genotype (HLA-DQA1*05 and HLA-DQB1*02) (homozygous or heterozygous) ­ Previous testing of blood must be performed at a Clinical Laboratory Improvement Amendments (CLIA) or equivalently certified laboratory. The details of the genotype assay methods must be recorded in the CRF. ­ Patients without available previous test results for HLA genotyping must submit a blood sample to determine whether an eligible HLA-DQ2.5 genotype is present by the central testing.
• Experienced at most mild symptoms of celiac disease within the month before screening. At screening patients are required to have either no symptoms or less than 2 mild symptoms on the CDSD scale in the 14 days recording period. ­
  • If the investigator determines that symptoms reported on the CDSD scale at screening are not due to celiac disease, the symptoms can be excluded from the judgment of patient eligibility.;
  • CDSD record reported in the original screening period can be used for eligibility judgement of sponsor-approved selective extension of the screening or rescreening when patient report the CDSD scale for the 14 days within 28 days prior to Day 1 and those frequency and severity of symptoms reported on CDSD during that time meet the criteria.

• Refractory celiac disease according to “The Oslo definitions for coeliac disease and related terms” (i.e., persistent or recurrent malabsorptive symptoms and signs with villous atrophy despite a strict GFD for more than 12 months).
• Positive for any of the 3 serology tests within the month before screening or during screening period ­ Tissue transglutaminase-2 [tTG2-IgA] (≥10 U/mL; normal range: 0–3.99 U/mL), but weak positive (4–10 U/mL) is acceptable. ­ Deamidated gliadin peptide-IgA [DGP-IgA] (≥30 U; normal range: 0–20 U), but weak positive (20–30 U) is acceptable. ­ Deamidated gliadin peptide-IgG [DGP-IgG] (≥30 U; normal range: 0–20 U), but weak positive (20–30 U) is acceptable.
• History of hypersensitivity reactions including anaphylaxis to a biologic medical product or any of the excipients.
• Any medical condition that, in the opinion of the investigator, would impact the immune response (other than celiac disease), confound interpretation of study results, or pose an increased risk to the patient.
• Previous participation in this study.
• Participation in an investigational study involving non-biologic therapy within 30 days or 5 half-lives of the investigational product (whichever is greater) prior to screening.
• Participation in an investigational study involving biologic therapy (including vaccines) within 90 days or 5 half-lives of the investigational product (whichever is greater) prior to screening unless they are known to have only received placebo.
• Participation in immune tolerance study where they received an immune-tolerogenic agent for celiac disease within 12 months prior to screening.
• Helicobacter pylori tests that indicate current infection.
• Any known active infection (with the exception of fungal nail infections or oral herpes).
• Any diseases known to increase the risk of developing serious complications from infectious disease (e.g., severe asthma, uncontrolled type 1 and type 2 diabetes).
• Any major episode of infection requiring hospitalization or treatment with intravenous (IV) anti-microbials within 8 weeks prior to and during screening or treatment with oral anti-microbials within 2 weeks prior to and during screening. ­ Antimicrobials include antifungal, antibacterial, and antiviral agents.
• History of invasive fungal infections such as Candida or Aspergillus (excluding thrush or other superficial fungal infections) within 6 months prior to screening.
• History of any other opportunistic infections within 12 weeks prior to screening.
• History of organ transplant.
• History of or currently active primary or secondary immunodeficiency.
• Positive human immunodeficiency virus (HIV) antibody test at screening.
• Positive hepatitis B surface antigen (HBsAg) test or positive both total hepatitis B core antibody test and hepatitis B virus deoxyribonucleic acid (DNA) test at screening.
• Positive hepatitis C virus (HCV) antibody test at screening, except in patients who have negative results for HCV ribonucleic acid (RNA) test at screening.
• Positive for tuberculosis (TB) during screening or within 3 months prior to screening, as a positive QuantiFERON®-TB Gold test (QFT) or (if QFT is not available) a positive purified protein derivative (PPD) skin test according to Centers for Disease Control and Prevention guidelines, with the following exceptions: ­ Patients with a history of Bacillus Calmette-Guérin (BCG) vaccination who have a positive PPD skin test will not be excluded if they have a negative QFT at screening ­ Patients who have a positive or indeterminate QFT and patients with no history of BCG vaccination who have a positive PPD skin test will not be excluded if they meet all of the following criteria
  • No symptoms consistent with TB;
  • Documented history of a completed course of adequate prophylaxis (completed treatment for latent TB) per local standard of care prior to screening;
  • No known exposure to a case of active TB after most recent prophylaxis;
  • No evidence of active TB on chest X-ray performed during screening or within 3 months prior to screening.
• History or presence of an abnormal ECGs that is clinically significant in the investigator’s opinion (for example, bundle-branch blocks, Mobitz type II second- or third-degree atrioventricular block, symptomatic or intervention-required Mobitz type I- or first degree- atrioventricular block or evidence of prior myocardial infarction).
• Clinically significant ECG abnormalities at screening such as the following: ­ The average QT interval with Fridericia’s correction of triplicate-measurements in supine position at 10-minute rest > 450 msec for male and > 470 msec for female ­ Bradycardia at rest (average heart rate 100 bpm).
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of long QT syndrome.
• Current treatment with medications that are known to cause QT interval prolongation.
• Pregnant or breastfeeding, or intending to become pregnant during the study or for at least 5 half-lives of DONQ52 after the final dose. ­ Women of childbearing potential must have a negative serum pregnancy test result within 30 days prior to initiation of DONQ52/placebo administration.
• History of hyposplenism. ­ Patients with encapsulated bacteria vaccine (e.g., haemophilus influenza type b vaccine, pneumococcal conjugate vaccine) will be permitted.
• History of recurrent bacterial, viral, mycobacterial or fungal infections (defined as > 2 similar episodes requiring anti-microbial treatment within the previous 12 months), with the exception of recurrent oral or genital herpes (HSV1/HSV2) or uncomplicated urinary tract infection (excluding pyelonephritis or urosepsis).
• Patients who have ongoing clinically significant manifestations which are dependent on nutrient deficiencies. (e.g. iron, vitamin D, calcium, vitamin B12/B6, folic acid, magnesium, zinc, vitamin K). 29). Any uncontrolled complications of celiac disease (e.g., enteropathy associated T-cell lymphoma, ulcerative jejunitis, intestinal perforation).
• Any uncontrolled other autoimmune disease. ­ Autoimmune thyroid disease that is euthyroid or stable on thyroid replacement therapy is acceptable.
• Any other chronic, active gastrointestinal disease (e.g., inflammatory bowel disease, microscopic colitis, peptic ulcer, gastroesophageal reflux disease, functional dyspepsia, or irritable bowel syndrome).
• Evidence of clinically significant cardiac, neurologic, psychiatric, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled type 1 and type 2 diabetes mellitus), metabolic, or gastrointestinal disease that, in the investigator’s opinion, would preclude patient participation.
• History of cancer, including hematologic malignancy and solid tumors, within 5 years prior to screening. ­ Basal or squamous cell carcinoma of the skin that has been excised and is considered cured and in situ carcinoma of the cervix treated with apparent success by curative therapy > 1 year prior to screening are not exclusionary.
• History of a live attenuated vaccine within 6 weeks prior to screening or requirement to receive these vaccinations at any time during study drug treatment or for at least 5 half-lives of DONQ52 after the final dose of study drug treatment. ­ For Seasonal influenza, H1N1, if the inactivated vaccine formulation is administered, history of vaccination 7 days prior to initiation of DONQ52/placebo dosing or requirement to receive these vaccinations prior to the timing of judgment on cohort / part transition. For COVID-19 vaccination, history of vaccination 14 days prior to screening/ rescreening or requirement to receive these vaccinations prior to the timing of judgment on cohort/part transition.
• Planned surgery during the study (including tooth extraction).
• Illicit drug, recreational drug (including medical use of marijuana / cannabis) or alcohol abuse within 12 months prior to screening, in the investigator’s judgment.
• Blood donation within 6 weeks prior to screening and plasma donation within 2 weeks prior to screening.
• Blood transfusion within 8 weeks prior to screening.
• Poor peripheral venous access.
• The following exclusion criteria are based on screening laboratory tests. Laboratory tests may be repeated once during the screening period unless otherwise indicated: ­ eGFR 1.5 × upper limit of normal (ULN). chronic hepatitis that may progress to cirrhosis, liver cirrhosis or portal hypertension. ­ Total bilirubin >1.5 × ULN (may be repeated if 1.5–3 × ULN). Total bilirubin >2 × ULN, in case that gilbert’s syndrome can be confidently diagnosed, which is unconjugated hyperbilirubinaemia, accompanied by:
  • Conjugated bilirubin is within the normal range and/or < 20% of total bilirubin;
  • Other liver enzymes and albumin are within the normal range;
  • No additional symptoms or signs which suggest hepatobiliary disease;
  • A negative hemolysis screen (normal hemoglobin and reticulocyte count, and no fragmented or abnormal red cells on blood film);
  • Hemoglobin < 10 g/dL (may be repeated if < 10 g/dL);
  • Absolute Neutrophil count (ANC) < 1.5 × 10^9 /L (may be repeated if 1.0–1.5 × 10^9 /L);
  • Platelet count < 150 × 10^9 /L (may be repeated if 80–150 × 10^9 /L) ­ IgG < 500 mg/dL (should not be repeated);
  • Serum IgA below detectable range;
  • Abnormalities in hepatic synthetic function tests (e.g., prothrombin time [PT], international normalized ratio [INR], partial thromboplastin time [PTT], albumin) judged by the investigator to be clinically significant.
• Use of immune checkpoint inhibitors (e.g., ipilimumab) within 60 months prior to screening.
• Use of agents that deplete B or T cells (e.g., rituximab, alemtuzumab or visilizumab) within 60 months prior to screening.
• Use of immunomodulatory or immune-suppressing medical treatment during the 6 months prior to screening (e.g., azathioprine, methotrexate, Jak inhibitors or biologics).
• Use of oral or parenteral corticosteroids within the 4 weeks prior to screening. ­ Topical or inhaled corticosteroids are acceptable.
• Use of intravenous (or subcutaneous) immunoglobulin G (IVIG) or plasmapheresis within 4 weeks prior to screening.
• History of myeloablative chemotherapy or bone marrow of stem cell transplantation.
• Chronic nonsteroidal anti-inflammatory drugs (NSAIDs) use ­ Occasional use (< 3 times per week) of NSAIDs or acetaminophen (e.g., for headache, arthritis, myalgias, or menstrual cramps) and aspirin up to 325 mg/day is permitted.
• Planning to initiate to take any new oral probiotic supplements (not including probiotics contained in commercially available food preparations) or to terminate any probiotic supplements which have been taken at screening timing during treatment period
• A patient is eligible if his/her oral probiotic regimen is stable for at least 2 weeks prior to randomization.

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

Eligibility last updated 11/16/23. Questions regarding updates should be directed to the study team contact.

• English speaking subjects with a suspected CVF, known CVF, or healthy control subjects.

• Subjects who are not English speaking.

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

 Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation of AFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG) beta > 100 mIU/mL. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers and cytology must be within 21 days prior to enrollment and within 35 days prior to start of protocol therapy [repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be within 7 days prior to enrollment and start of protocol therapy [repeat if necessary]). Basal ganglia or other primary sites are excluded.

- Patients with any of the following pathological elements are eligible: endodermal sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant elements listed above are present. Patients with only mature teratoma are excluded.
Patients with pure germinoma admixed with mature teratoma are excluded (would be eligible for pure germinoma protocols).

- Patients must have a cranial magnetic resonance imaging (MRI) with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post operative brain MRI with and without gadolinium. The post operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not
required (within 14 days prior to study enrollment).

- Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment. Spine MRI with and without gadolinium is recommended (within 14 days prior to study enrollment).

- Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days
following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery.

- Patients must have CSF tumor markers obtained prior to enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first.

- Peripheral absolute neutrophil count (ANC) ≥ 1000/uL (within 7 days prior to enrollment).

- Platelet count ≥ 100,000/uL (transfusion independent) (within 7 days prior to enrollment).

- Hemoglobin ≥ 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days prior to enrollment).

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):

- Age: Maximum serum creatinine (mg/dL);
- 3 to < 6 years: 0.8 (male), 0.8 (female);
- 6 to < 10 years: 1 (male), 1 (female);
- 10 to < 13 years: 1.2 (male), 1.2 (female);
- 13 to < 16 years: 1.5 (male), 1.4 (female)'
- ≥ 16 years: male (1.7), 1.4 (female).

- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment).

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 135 U/L (within 7 days prior to enrollment).

- Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L.

- Central nervous system function defined as:

- Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled;

- Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment.

- Protocol therapy must begin within 31 calendar days of definitive surgery or clinical diagnosis. If a biopsy only was performed, the biopsy date will be considered the date
of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery.

- All patients and/or their parents or legal guardians must sign a written informed consent.

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

- NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:

- English-, Spanish-, or French- speaking;

- Note: Patients who speak a language other than English, Spanish, or French will be allowed to participate in ACNS2021 but will not complete the neurocognitive
and quality of life assessments.

- No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g., Down syndrome, fragile X, William syndrome, intellectual disability). Patients with
NF1 will be allowed to participate.

- Additional eligibility criteria for the COG Standardized Neuropsychological Battery only: must be at a site that has a psychologist to administer the battery.

- Note: If not eligible for the COG Standardized Battery, patients should still complete the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior
Assessment System Third Edition (ABAS-3), and Behavior Assessment System for Children, Third Edition (BASC-3) questionnaires.

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

Eligibility last updated 8/30/22. Questions regarding updates should be directed to the study team contact.

• Subject experienced a severe EoE flare requiring endoscopic intervention and/or concomitant rescue therapy during the Induction Phase and has completed Week 24 of the Induction Phase; OR
• Subject completed the Induction Phase and does not qualify for entry to the Maintenance Phase for reasons other than a severe EoE flare; OR
• Subject experienced a severe EoE flare requiring endoscopic intervention and/or concomitant rescue therapy during the Maintenance Phase and completed Week 48 of the Maintenance Phase; OR
• Subject completed Week 48 of the Maintenance Phase; OR
• Subject must have participated in Study CC-93538-DDI-001 and completed assessments
• through the end of treatment visit.

- Demonstrated ≥ 80% and ≤ 120% overall compliance with required investigational product dosing during the prior studies.

- Did not permanently discontinue investigational product in the prior studies and/or did not experience any clinically significant adverse events related to Investigational Product that would preclude further dosing in the opinion of the
Investigator.

- Female subject of childbearing potential must agree to practice a highly effective method of contraception. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly. A female of childbearing potential (FCBP) is a female who:

• has achieved menarche at some point; and
• has not undergone a hysterectomy or bilateral oophorectomy or bilateral salpingectomy; or
• has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• An FCBP must:
  • Have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy in Study CC-93538-EE-001 or Study CC-93538-DDI-001 and an additional negative result prior to continuing study therapy in the OLE. She must agree to ongoing pregnancy testing during the course of the study and through the Final 16-week Safety Follow-up Visit. This applies even if the subject practices true abstinence* from heterosexual contact;
  • Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, highly effective contraception without interruption throughout the study and for 5 months after the last dose of IP. Acceptable methods of birth control in this study are the following and as applicable per national and local regulations (birth control must be effective by the time the FCBP subject is randomized into the study [e.g., hormonal contraception should be initiated at least 28 days before randomization]):  combined hormonal (estrogen and progestogen containing) contraception, which may be oral, intravaginal, or transdermal Note: Intravaginal and transdermal combined hormonal contraception are not approved in Japan and would therefore not be an acceptable method of contraception for subjects enrolled in this region.
  • progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable Note: progestogen-only hormonal contraception is not approved in Japan and would therefore not be an acceptable method of contraception for subjects enrolled in this region;
  • placement of an intrauterine device (IUD);
  • placement of an intrauterine hormone-releasing system (IUS);
  • bilateral tubal ligation; or bilateral tubal occlusion (if an implantable device was recently placed, the subject must use an additional effective method of birth control until full occlusion has been confirmed and documented);
  • vasectomized partner (vasectomized partner is a highly effective birth control method provided that the partner is the sole sexual partner of the FCBP and has received medical assessment of the surgical success);
  • sexual abstinence.

Eligibility last updated 12/27/23. Questions regarding updates should be directed to the study team contact.

In the study eye since randomization,
new retinal detachment, or retinal tear
that, in the opinion of the investigator,
may preclude successful subretinal
injection of ABBV-RGX-314.

New subfoveal fibrosis or subfoveal atrophy since randomization, as defined in subbullets below, or any condition preventing VA improvement in the study eye.
•Central subfield fibrosis (central 1mm) in the study eye, as determined by the CRC.
•Any central subfield atrophy (central 1mm) in the study eye (eg, incomplete RPE and outer retinal atrophy, or complete RPE and outer retinal atrophy), as determined by the CRC.

3. Ocular or periocular infection or intraocular inflammation in the study eye that may interfere with the surgical procedure.

4. Myocardial infarction, cerebrovascular accident, or transient ischemic attacks since randomization.

5. Uncontrolled hypertension (systolic BP >180 mmHg, diastolic BP > 100 mmHg) despite maximal medical treatment.

History of malignancy or hematologic malignancy that may compromise the immune system requiring chemotherapy and/or radiation since randomization. Localized basal cell carcinoma will be permitted, as will any cancer not being treated with chemotherapy or other therapy that may compromise the immune system.

Polypoidal choroidal vasculopathy in the study eye, as determined by the investigator or the CRC.

7. Any subretinal hemorrhage in the study eye > 50% of the total lesion area or within the parafovea (3-mm center of the macula), as determined by the CRC.

8. Presence of any retinal pigment epithelial tear involving the central subfield (central 1 mm) in the study eye, as determined by the CRC.

9. Any prior nAMD treatment with photodynamic therapy or retinal laser in the study eye.

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

Eligibility last updated 10/25/23. Questions regarding updates should be directed to the study team contact.

- Willing to not start or stop any new medication to treat or prevent migraines during the six months of the trial.

- History fits the definition of migraine:

- Have a history of episodic headache lasting 4-72 hours with at least 2 of the 4 following: unilateral location, pulsating/throbbing quality, moderate-severe
intensity, aggravation by/causing avoidance of routine physical activity; and

- Have a history of at least one of the following: nausea and/or vomiting, photophobia (seek out a dark room during a headache because that feels better), phonophobia (seek out a quiet environment during a headache because that feels
better).

- Barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, cream, or gel that kills sperm);

- Intrauterine device (IUD);

- Total hysterectomy or tubal ligation;

- Abstinence (no sex).

- Allergy or documented contraindication to amide anesthetics (bupivacaine, lidocaine, ropivacaine, prilocaine, mepivacaine, etidocaine or levobupivacaine) or
corticosteroids.

- Previously received peripheral nerve blocks (PNBs).

- Currently anticoagulated.

- Currently receiving Botox for migraine prophylaxis.

- Started on new medication in the prior two months with known migraine-preventive efficacy or planning to start any new medication during the study.

- Currently using opiate medications for pain.

- History of drug or alcohol abuse within the prior two years.

- Have unstable medical or surgical diseases that could impair participation in this study.

- History of craniotomies, burr holes, skull fractures and/or have open skull defects.

- Patients with implanted nerve stimulators or shunts.

- Phobia of needles.

- Active skin or soft tissue infection overlying injection sites.

- Diagnosis of medication overuse, cervicogenic, post-traumatic, or cluster headaches or history on pre-enrollment questionnaire of cluster headache symptoms.

Eligibility last updated 7/24/23. Questions regarding updates should be directed to the study team contact.

• Men or women.
• 22 to 80 years old.
• Unruptured cerebral aneurysm scheduled for flow diverter treatment at St. Marys Hospital.
• Patients who may require pre-treatment with Lorazepam/Ativan prior to MRI scanning provided they have an adult accompanying and driving for them after the scan is completed.

• Any prior stent or coil treatments.
• IVC filter removal in last twelve months.
• Unable to have MRI imaging exams due to coil, filter, stent or wire or an implanted device such as IVC filter, pacemaker, nerve stimulator, medication pump or other on body injector delivery system/sensor or tattoo ink that if it contained metal could heat up and/or or generate image artifact.  
• Not able to return for follow-up MRI imaging and blood collection in three to twelve months post flow diversion (FD) treatment.
• Pregnant or breast-feeding females.
• Cancer diagnosis and having had (last twelve months) or currently undergoing radiation and/or chemotherapy treatments.
• Persons lacking capacity.
• Prisoner.

Eligibility last updated 8/30/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 8/16/22. Questions regarding updates should be directed to the study team contact

Inclusion Criteria - MAD Stage:

• Signed Informed Consent Form.
• Age 18-75 years at time of signing Informed Consent Form.
• Weight of 45-150 kg at screening.
• Ability to comply with the study protocol.
• Diagnosis of SSc, as defined by 2013 ACR/EULAR criteria.
• 10 years disease duration from first non-Raynaud’s sympto.
• For patients with dcSSc, ≥ 15 mRSS units at screening and baseline and with skin available for biopsy preferably on proximal forearms having mRSS ≥ 2 at the biopsy location (alternative sites with relevant mRSS scores may be biopsied).
• For patients with lcSSc, ≥ 9 mRSS units at screening and baseline and with lesional skin available for biopsy preferably on proximal forearms having mRSS ≥ 2 at the biopsy location (alternative sites with relevant mRSS scores may be biopsied).

Inclusion Criteria
•Open-Label Safety Extension Stage:

• Signed OSE Informed Consent Form.
• No clinically significant change in eligibility status The urine drug screen and viral serology need not be repeated unless clinically indicated.
• Completion of the MAD Day 113 (first 5 dose-escalation patients per cohort) or Day 85 (all other patients without withdrawal from treatment) and ability to roll over into the OSE within 5 days.
• Patients on stable doses of MMF, MTX, HCQ, AZA, SSZ, TCZ, and/or oral corticosteroids should not have the prospective intent to discontinue or change the dose over the 52-week duration of the OSE; and patients not already on a stable dose of any of the aforementioned therapies should not have a prospective intent to initiate treatment during the course of the OSE treatment period.

• Active rheumatic autoimmune disease other than SSc requiring treatment with disease-modifying therapy, including, but not limited to, RA, systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, dermatomyositis, eosinophilic fasciitis, primary Sjögren syndrome, eosinophilic myalgia syndrome, and pneumonitis, as determined by the investigator.
• Pulmonary disease with FVC.
• 50% of predicted.
• Known pulmonary arterial hypertension (PAH; WHO Class II or higher), as determined by the investigator.
• Recent history (within 3 months for any of the following) of root canal, unresolved dental infection, poor dentition, Grade ≥ 2 gingival or periodontal disorders (e.g., hyperplasia, inflammation, bleeding), and/or dental implant placement.
• History or clinical manifestations of significant metabolic, hepatic, renal, pulmonary, cardiovascular, hematologic, gastrointestinal, urologic, neurologic, or psychiatric disorders that may impact safe participation for the duration of the trial, as determined by the investigator.
• History of uncontrolled hypertension.
• History of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer.
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies.
• History of solid organ or stem-cell transplantation.
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study.
• History or presence of an abnormal ECG that is deemed clinically significant by the investigator, including complete left bundle branch block, second- or third-degree atrioventricular heart block, or evidence of prior (within last 12 months) myocardial infarction.
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), or family history of sudden unexplained death or long QT syndrome.
• History of aortic disease or any clinically significant abnormality on the screening echo, including evidence of aortic disease (e.g., dissection, aneurysm), or LVEF 50% or below the LLN.
• History of stroke (ischemic or hemorrhagic) or transient ischemic attack or other significant vascular disease (e.g., recent peripheral arterial thrombosis) within 6 months prior to initiation of study treatment.

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

Eligibility last updated 10/5/23. Questions regarding updates should be directed to the study team contact.

• Diagnosis of a DSM-5 restrictive eating disorder (anorexia nervosa or other specified feeding or eating disorder characterized by dietary restriction and/or weight loss or failure to make expected weight gains).
• Eligible patients will have at least one caregiver who is also willing to participate in the study.
• Eligible patients must receive primary care through one of 3 MCHS sites connected to the study: Onalaska/La Crosse, Redwing, and Faribault.

• Patients will be excluded who have received FBT in the past, and/or who report active suicidality.
• Patients who become physically or psychiatrically unstable during the study will be re-evaluated and referred for appropriate treatment.
• Patients will be excluded if their enrolled caregiver has active substance  dependence, mental health concerns that make it difficult to engage in treatment, or are perpetrators of abuse.

Eligibility last updated 11/10/22. Questions regarding updates should be directed to the study team contact.

• > 18 years of age.
• Chronic wound in the course of diabetic foot ulcers and/or lower extremity venous ulcers with duration of at least 6 weeks and the wound surface not less than 2 sq. cm and not greater than 15 sq. cm, without evidence of active infection of the wound at the time of qualification to participate in the study.
• For chronic venous ulcers, ultrasound demonstrates venous reflux >0.5 seconds.
• Satisfactory blood glucose control -, HbA1c < 7.5%.
• Satisfactory blood supply to the wound verified by the measurement of the oxygen level of the foot tissue (TCPO2 > 30mmHg) in patients with neuropathic etiology of diabetic foot syndrome.
• We have duration of at least 6 weeks above.
• Ankle-brachial index (ABI) ≥ 0.8. If vessels are non-compressible and no ABI is therefore able to calculated, then TCPO2 needs to be >30 mmHg.
• Diabetic patients often have calcified non-compressible vessels, need to ensure TcPO2 is adequate.

• ≤ 18 years of age.
• Acute wound with duration less than 6 weeks.
• Evidence of active infection or on antibiotics.
• Smoker.
• For chronic venous ulcers, ultrasound demonstrates venous reflux < 0.5 seconds.
• Unsatisfactory blood glucose control
  •HbA1c > 7.5%.
• Poor blood supply to the wound verified by the measurement of the oxygen level of the foot tissue (TCPO2 < 30mmHg) in patients with neuropathic etiology of diabetic foot syndrome or mixed venous arterial wounds.
• Ankle-brachial index (ABI) < 0.8.
• Pregnancy.
• Known allergy to lidocaine.

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

Eligibility last updated 10/30/23. Questions regarding updates should be directed to the study team contact.

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

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