Inclusion Criteria - Neurodegenerative Disease and Disorders :

• Age and gender matched to healthy participants with no known neurodegenerative disorder.
• Absence of primary psychoses including schizophrenia, bi-polar disorder or other (patients with co-morbid depression can be included)
• Ability to give, with or without caretaker, verbal or written consent.
• Currently diagnosed with AD, PDD, DLB, or MCI [(McKhann et al., 2011) (Emre et al., 2007), (McKeith et al., 2017), (Albert et al., 2011)] .

Exclusion Criteria
•Neurodegenerative Disease and Disorders:

• Recent (past 5 years) head injury, or older head injury with current symptoms.
• Regular (daily) use of opiate pain medications.
• Any eating disorders (anorexia, bulimia).
• History of marijuana/cannabis use (amount/ times per week).
• Excessive tobacco use (i.e. more than 10 cigarettes a day).
• Excessive alcohol (> 5 drinks daily) or caffeine (>10 cups daily).
• Any known clinically significant pulmonary (lung) disorders.
• Untreated/untreatable vision or hearing problems.
• Pregnant or nursing.
• Inadequate familiarity with the English language.
• Older than 90 years of age or younger than 40 years of age.

Inclusion Criteria
•Healthy Controls:

• Age and gender matched to patients diagnosed with neurodegenerative disorder.
• Absence of a neurological or psychiatric illness.
• Ability to give verbal and written consent.

Exclusion Criteria
•Healthy Controls:

• Any known sleep disorder (e.g., narcolepsy, severe sleep apnea, chronic insomnia).
• Recent (past 5 years) head injury, or older head injury with current symptoms.
• Regular use of opiate pain medications.
• Any eating disorders (anorexia, bulimia).
• Current use or a history of use of stimulants (e.g., amphetamine) or substance abuse.
• History of marijuana/cannabis use (amount/ times per week).
• Excessive tobacco use (i.e. more than 10 cigarettes a day).
• Any known neurological or psychiatric illnesses.
• Excessive alcohol (> 5 drinks daily) or caffeine (> 7 cups daily).
• Any known clinically significant pulmonary (lung) disorders.
• Untreated/untreatable vision or hearing problems.
• Pregnant or nursing.
• Inadequate familiarity with the English language.
• Older than 90 years of age or younger than 40 years of age.

Exclusion Criteria
•All Participants:

• Heart failure (i.e., myocardial infarction).
• Epilepsy (current episodes and medication in the past year).
• Known AIDs (HIV+) diagnosis
• Bipolar disorder.
• Severe/psychotic depression requiring immediate psychiatric hold because of danger to self or others. 

PSG SubStudy Only:

Inclusion Criteria
•REM sleep behavior disorder:

• Fulfill criteria for RBD based on polysomnography according to the standard International Classification of Sleep Disorders diagnostic criteria, 3rd edition (American Academy of Sleep Medicine 2014).
• Age and gender matched to healthy participants with no known neurodegenerative disorder.

Exclusion Criteria - (REM sleep behavior disorder):

• Recent (past 5 years) head injury or older head injury with current symptoms.
• Inadequate familiarity with the English languageepilepsy (current episodes and medication in the past year).
• Known AIDs (HIV+) diagnosis.
• Severe/psychotic depression requiring immediate psychiatric hold because of danger to self or others.

Inclusion Criteria
•Healthy Controls:

• Age and gender matched to patients diagnosed with REM sleep behavior disorder.
• Absence of a neurological illness.
• Ability to give verbal and written consent.

Exclusion Criteria
•Healthy Controls:

• Any known neurological illnesses.
• Iadequate familiarity with the English language.
• Known AIDs (HIV+) diagnosis.
• Severe/psychotic depression requiring immediate psychiatric hold because of danger to self or others. 

• Patients will not be excluded for controlled hypertension, diabetes, high cholesterol, mild to moderate sleep apnea or depression.
• Medical marijuana use will not be a cause for excluding a participant; however, current use will be documented.

• Males and females aged ≥ 18 years (or ≥ 19 years according to local regulatory guidelines) at the time of screening.
• Has adequate organ and marrow function as defined in protocol.
• Measurable disease as per RECIST v1.1.
• ECOG performance status 0-1.
• Adverse events related to any prior chemotherapy, radiotherapy, immunotherapy, other prior systemic anti-cancer therapy, or surgery must have resolved to Grade ≤1, except alopecia and Grade 2 peripheral neuropathy.
• HIV infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease as defined in protocol.

• Has known active CNS metastases and/or carcinomatous meningitis.
• An active second malignancy.
• Has active or a known history of Hepatitis B or known active Hepatitis C virus infection.
• Has active tuberculosis or has a known history of active tuberculosis.
• Active or uncontrolled infections, or severe infection within 4 weeks before study treatment administration.
• History of chronic liver disease or evidence of hepatic cirrhosis, except patients with liver metastasis.
• Has an active autoimmune disease that has required systemic treatment in past 2 years.
• Previous immunotherapies related to mode of action of GI-102.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive medications within 2 weeks prior to Cycle 1 Day 1.
• Administration of prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment.
• Radiotherapy within the last 2 weeks before start of study treatment administration, with exception of limited field palliative radiotherapy.
• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1.
• Known hypersensitivity to any of the components of the drug products and/or excipients of GI-102.

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

• Non-Infectious Active Uveitis of the posterior segment of the eye.

• Females who are pregnant, nursing, or planning a pregnancy.
• Confirmed or suspected infectious uveitis.

Two cohorts of patients are planned to be enrolled in the study:

• “New user”: patients starting osilodrostat at study entry;
• “Prior user”: patients that have started osilodrostat any time prior to study entry.

InclusIon Criteria:

• Written informed consent obtained prior to registration of any patient data.
• Male or female patients, aged 18 years or older
• Diagnosed with endogenous Cushing's Syndrome (CS).
• Treated with osilodrostat. Treatment with osilodrostat can either be initiated at the first visit of the study or can have been initiated before screening.

• Patients with exogenous CS.
• Patients with Pseudo CS.
• Patients participating in an interventional clinical trial with an investigational drug.

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

• Age ≥ 18 years old.
• Clinical and radiographic evidence suggesting CNS malignancy.
• Suspected newly diagnosed, local, or intracranial recurrence of primary brain tumor OR Previously untreated or treated brain metastasis.
• Willing to undergo a neurosurgical resection of CNS lesion at Mayo Clinic Rochester.
• Able to have MRI imaging with gadolinium contrast (e.g., no cardiac pacemaker, defibrillator, renal failure).
• Females of childbearing potential must have a negative pregnancy test done < 14 days prior to registration.
• Provide written informed consent.
• Willing to provide tissue and blood samples for research purposes
• For patients having a study-specific surgical planning MRI only.  The following lab values obtained ≤ 30 days prior to registration:
  • Creatinine (eGFR ≥ 30).

• Vulnerable populations: pregnant women, prisoners, mentally handicapped.
• Unable to undergo a biopsy of CNS lesion.
• Documented drug allergy to cefazolin, levetiracetam, or other study drugs, or other contraindication to use these drugs in the pre-operative setting (e.g., patient is already on another anti-seizure medication which precludes the clinical indication for pre-operative levetiracetam).
• Patients who are unable to swallow tablets if study drug is administered by mouth.
• Patients who are at risk for impaired absorption of oral medication if study drug is administered by mouth. Note: This includes but not limited to, refractory vomiting, gastric resection/bypass, and duodenal/jejunal resection.
• Pregnant or nursing women.
  • Note: Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects with chemotherapy. There is also a potential risk for AEs in nursing infants secondary to treatment of the mother with these drugs, so breastfeeding should be discontinued for the duration of the study.

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

Eligibility last updated10/11/22. Questions regarding updates should be directed to the study team contact.

• Subjects with target disease ONFH and OA.

• ONFH and OA subjects taking the medications statins, steroids, or TZDs will be excluded. 

Pre-Screening Eligibility Criteria:

• Signed written informed consent to permit tissue analysis.
• 18 years of age or older.
• No medical history that is excluded per the study treatment eligibility criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Eligible for or receiving systemic therapy for inoperable or advanced iCCA.
• Not currently eligible for curative local or surgical therapy.
• To be enrolled in the study, once the FGFR2 genomic aberration status is determined, each prospective patient must meet all of the following inclusion criteria and none of the exclusion criteria.

• Signed written informed consent granted prior to initiation of any study-specific procedures.
• 18 years of age or older.
• Histologically or cytologically confirmed locally advanced, inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons), or metastatic iCCA or mixed histology tumors (combined hepatocellular-cholangiocarcinoma [cHCC-CCA]).

Substudy 1:

• FGFR2 fusion status based on the following assessments:
  • If central laboratory designated by the Sponsor: Positive FISH test; and/or
  • If non-central laboratory: *
  • Positive FISH or NGS test: patients may be enrolled and may start dosing, but central confirmation is required.**  
  • * Using standard protocols and approved by local IRB/IEC, CLIA, or other similar agency. For enrollment of patients in the EU, assays must be fully CE-marked. ** The patient must not be enrolled if a negative FISH test is obtained from the central laboratory prior to commencing study treatment. Patients without central confirmation of an FGFR2 fusion by the central FISH test will be assessed on a case-by-case basis.
• Negative FISH or NGS test: tissue may be submitted to the central laboratory designated by the Sponsor, and patients may only be enrolled if the central test is positive.

Substudy 2:

• FGFR2 mutations/amplifications without any concurrent FGFR2 translocations based on NGS testing performed or commissioned by the respective study site (see Section 6.8.2 for further details).
  • Note 1: If the FGFR2 mutation/amplification status is derived from plasma-based NGS testing, a tumor block or slides prepared thereof should be submitted for subsequent correlative tissue-based NGS test at a laboratory identified by the Sponsor.
  • Note 2: If the NGS test used cannot identify FGFR2 translocations, a FISH test is mandatory to confirm that none are present.
• Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression (for Substudy 1), and have no satisfactory treatment alternatives (for Substudy 2)
• Measurable disease by RECIST version 1.1 criteria.
• ECOG performance status ≤ 1.
• Adequate organ functions as indicated by the following laboratory values (based on screening visit values from the central laboratory):
  • Hematological
    • Hemoglobin (Hgb) ≥ 9.0 g/dL;
    • Absolute neutrophil count (ANC)  ≥ 1.5 × 10^9/L;
    • Platelet count ≥ 75 × 10^9/L;
    • International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or ≤ 3 for patients receiving anticoagulant therapy such as warfarin or heparin.
  • Hepatic
    • Total bilirubin ≤ 2 × ULN;
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 ULN (≤ 5 × ULN for patients with liver metastases);
    • Albumin ≥ 2.8 g/dL.
  • Renal
    • Serum creatinine ≤ 1.5 × ULN; or
    • Creatinine clearance of ≥ 30 mL/min as estimated by the Cockcroft-Gault equation.
• Female and male patients of child-producing potential must agree to avoid becoming pregnant or impregnating a partner, respectively, during the study*, and for at least 120 days after the last dose of derazantinib.
• Male patients are considered not to be of child-producing potential if they have azoospermia (whether due to vasectomy or an underlying medical condition). Female patients are considered not to be of child-producing potential if they are:
  • postmenopausal†; or
  • have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; or
  • have a congenital or acquired condition that prevents childbearing.
• Male or female patients of child-producing potential must agree to comply with one of the following until at least 120 days after the last dose of derazantinib:
  • Abstinence from heterosexual activity‡;
  • Using (or having their partner use) a highly effective method of contraception during heterosexual activity.  Highly effective methods of contraception are§:
    • an intrauterine device (IUD);
    • vasectomy of a female patient’s male partner;
    • a contraceptive rod implanted into the skin;
    • combined (estrogen- and progestogen-containing) or progestogen-only hormonal contraception associated with inhibition of ovulation (oral contraceptive pill [estrogen/progestin pill or progestin-only pill] contraceptive skin  patch/implant, vaginal contraceptive ring, or subcutaneous contraceptive injection).
• *From the day of first study medication, or for oral contraception from 14 days before first study medication.
• † Postmenopausal is defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post -menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is not sufficient.
• ‡ Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject’s preferred and usual lifestyle and if it is employed during the entire period of risk associated with the study treatment and if it is considered highly effective by local regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not highly effective methods of contraception.
• § If a contraceptive method listed above is restricted by local regulations/guidelines, then it does not qualify as a highly effecive method of contraception for subjects participating at sites in this country/region.

• Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable:
  • One chemotherapy or biological (e.g., antibody) cycle interval;
  • Five half-lives of any small-molecule investigational or licensed medicinal product;
  • Two weeks, for any investigational medicinal product with an unknown half-life;
  • Four weeks of curative radiotherapy;
  • Seven days of palliative radiotherapy;
  • 28 days of radiotherapy.
• Major surgery or locoregional therapy within 4 weeks of the first dose of derazantinib.
• Previous treatment with any FGFR inhibitor (e.g., Balversa® [erdafitinib], Pemazyre® [pemigatinib], infigratinib, rogaratinib, futibatinib, lenvatinib, ponatinib, dovitinib, nintedanib, AZD4547, LY2784455).
• Unable or unwilling to swallow the complete daily dose of derazantinib capsules.
• Clinically unstable central nervous system (CNS) metastases (to be eligible, patients must have stable disease  ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or have CNS metastases. well controlled by low-dose steroids, antiepileptics, or other symptom-relieving medications).
• Current evidence of clinically signficant corneal or retinal disorder likely to increase the risk of eye toxicity including, but not limited to, bullous/band keratopathy, keratoconjunctivitis (unless keratoconjunctivitis sicca), corneal abrasion, inflammation/ulceration, confirmed by ophthalmologic examination.
• Concurrent uncontrolled or active hepatobiliary disorders, untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, biloma or abscess (to be eligible, the patients have to be treated and disorders/complications should be resolved within 2 weeks prior to the first dose of derazantinib).
• History of significant cardiac disorders:
  • Myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of derazantinib (MI that occurred > 6 months prior to the first dose of derazantinib are permitted);
  • QTcF > 450 msec for men and QTcF > 460 msec for women.
• Serum electrolyte abnormalities defined as follows:
  • Hyperphosphatemia: serum phosphate > institutional ULN;
  • Hyperkalemia: serum potassium > institutional ULN;
  • Hypokalemia: serum potassium < institutional lower limit of normal (LLN);
  • Hypercalcemia: corrected serum calcium > 3.1 mmol/L (> 12.5 mg/dL);
  • Hypocalcemia: corrected serum calcium < 1.75 mmol/L (< 7.0 mg/dL);
  • Hypomagnesemia: < 0.4 mmol/L (< 0.9 mg/dL).
• Significant gastrointestinal disorder(s) that could, in the opinion of the Investigator, interfere with the absorption, metabolism, or excretion of derazantinib (e.g., Crohn’s disease, ulcerative colitis, extensive gastric resection).
• History of additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical cancer.
• Concurrent uncontrolled illness not related to cancer, including but not limited to:
  • Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements;
  • Known uncontrolled human immunodeficiency virus (HIV) infection.
  • Severe bacterial, fungal, viral, and/or parasitic infections under treatment with therapeutic oral or intravenous (IV) medication at the time of first dose of study drug administration.
• Blood or albumin transfusion within 5 days of the blood draw being used to confirm eligibility.
• Pregnant or breast feeding.
• Known hypsersensitivity to derazantinib, or to any of the study drug excipients (starch, lactose, crospovidone, magnesium stearate).

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

Eligibility last updated 9/15/23. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 7/20/22. Questions regarding updates should be directed to the study team contact.

• Adult males and females between 18 and 60 years of age, inclusive at the time of signing the informed consent document.
• Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
• Diagnosis of cyclic vomiting syndrome (CVS) using the Rome IV diagnostic criteria and must have:
  • Stereotypical episodes of acute onset vomiting lasting < 1 week;
  • At least 3 discrete episodes of vomiting in the prior year and 2 episodes in the past 6 months, occurring at least 1 week apart;
  • Absence of vomiting between episodes (but milder symptoms may be present);
  • Symptoms must be present for the past 3 months with onset at least 6 months prior.
• Has a prodrome or pre-emetic symptoms for approximately half of their “typical” CVS episodes.
• If of reproductive age, female participants and female partners of male participants, willing and able to use a medically highly effective form of birth control from at least 4 weeks prior to Baseline until at least 30 days following last dose of study drug. Examples of medically highly effective forms of birth control are:
  • Surgical sterility (hysterectomy or bilateral ligation) or post‑menopausal (cessation of menses for at least 12 months prior to screening);
  • Sexual partner is sterile, or of the same sex;
  • Implants of levonorgestrel in females;
  • Oral contraceptive (combined, patch, vaginal ring, injectable, implant) in females;
  • Double-barrier method (any combination of physical and chemical methods);
  • Intrauterine device with a failure rate less than 1% per year.
• Male participants must:
  • Agree to use, with their partners, one of the highly effective contraceptive methods listed in Inclusion Criterion 5, from Baseline until at least 30 days following last dose of study drug;
  • Refrain from donating sperm during the study and for at least 30 days after the end of the study.
• Otherwise healthy, as determined by the responsible physician, based on a medical evaluation including history, physical examination, vital signs, electrocardiograms (ECGs) and laboratory tests assessed at the screening visit.
• Negative urine tests for selected drugs of abuse and alcohol breath test at Screening.
• Note: Patients with a positive urine drug screen for benzodiazepines or opiates may be allowed in the study provided the drug was prescribed by a physician.
• Willing and able to adhere to overall study visit schedule, procedures and other protocol requirements.

• Any significant medical or psychiatric condition that could, in the Investigator’s opinion, compromise the subject’s safety or interfere with the completion of this protocol.
• Any condition, including the presence of laboratory abnormalities or pulmonary condition, which according to the Investigator places the subject at unacceptable risk if he/she were to participate in the study.
• A diagnosis of any gastrointestinal disorder other than CVS that in the judgement of the Investigator could compromise the subject’s safety or interfere with the interpretation of safety or efficacy data.
• History of clinically significant neurologic (e.g., seizures), cardiac, pulmonary (e.g., asthma, COPD), metabolic, renal, or hepatic conditions.
• Use drugs known to prolong QTc. ECG findings of PR interval > 220 msec or QRS duration > 120 msec or QTcF interval > 450 msec for men and 470 msec for women obtained at screening visit or prior to the first dose of study drug.
• Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), serum creatinine, or total bilirubin > 1.5 upper limit of normal (ULN) at screening or prior to the first dose of study drug. These laboratory tests may be repeated once, if they are abnormal on first screening, and if there is a medical reason to believe the results may be inaccurate. If the repeat test is within the reference range, the subject may be included only if the Investigator considers that the previous finding will not compromise the subject’s safety and will not interfere with the interpretation of safety data.
• Positive blood screen for human immunodeficiency virus (HIV antibody), hepatitis B virus surface antigen, or hepatitis C virus antibody at screening.
• History of alcohol or illicit drug abuse within 1 year before the first dose of study drug.
• Daily use of marijuana.
  • Note: Occasional use of THC/cannabinoid products is allowed in the study.
• Participation in a clinical trial and receipt of an investigational medication or a new chemical entity within 90 days, 5 half-lives, if known, or twice the duration of the biological effect of any medication (whichever is longer) prior to the first dose of current study drug.
• Donation of blood, plasma or other blood products or blood collection in excess of 470 mL within 8 weeks prior to dosing.
• Known history of sensitivity to any of the study drugs or components thereof, or to other 5-HT3 receptor antagonists, or a history of medication allergy or other allergy that, in the opinion of the Investigator, contraindicates study participation.
• Major surgery within 4 weeks of screening that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the Investigator.
• Uncontrolled current illness (i.e., active infection).
• Has a current or a history of cancer, with the exception of basal cell carcinoma.

Eligibility last updated 2/24/22. Questions regarding updates should be directed to the study team contact.

• Adult patients (age 18 and over).
• Active cancer diagnosis.
• Admitted to the inpatient setting.
• Grade 3-4 oral mucositis per the World Health Organization (WHO).
• Grade 3: soreness and erythema, able to eat solid food.
• Grade 4: soreness and erythema, able to tolerate liquid diet only.
• Patient reports oropharyngeal pain.
• Able to provide informed consent.

• Pediatric age (under 18 years old).
• Any contraindication to methylene blue.
• Pregnant women.

Eligibility last updated 10/25/22. Questions regarding updates should be directed to the study team contact.

• Patient must provide written or verbal informed assent and the parent/guardian/LAR must provide written informed consent before the initiation of any study-specific procedures.
• Patient is a male or female outpatient, 12 to 17 years of age inclusive, at the time the patient provides assent for the study and parent/guardian/LAR has provided signed consent.
• Patient is able to read and understand the assessments in the eDiary.
• Female patients of childbearing potential must have a negative serum pregnancy test at Visit 1 (screening) and a negative urine pregnancy test at Visit 3 (randomization) prior to dosing.
• Female patients who have had their first menstrual period and are sexually active must agree to use a reliable form of contraception. Reliable contraception is defined as:
  • Hormonal contraception (eg, oral contraceptive, contraceptive implant, or injectable hormonal contraceptive).
  • Double-barrier method (eg, condom plus intrauterine device, diaphragm plus spermicide).
• Patient has a diagnosis of IBS-D as defined by the modified Rome IV child/adolescent criteria*: Must include all of the following:
  •  Abdominal pain at least 4 days per month over at least 2 months associated with one or more of the following:
    •  Related to defecation
    •  A change in frequency of stool
    •  A change in form (appearance) of stool
  • After appropriate evaluation, the symptoms cannot be fully explained by another medical condition
  • Patient has predominantly diarrheal stool symptoms defined as Bristol stool types 6 or 7 for more than 25% of bowel movements and Bristol stool types 1 or 2 for less than 25% of bowel movements that occur in the absence of laxatives
• All criteria fulfilled for at least 2 months prior to Visit 1 (screening). 
• Patient has been compliant with the eDiary by completing both the morning and evening assessments for at least 8 out of the 14 days immediately preceding Visit 3 (randomization).
• Patient has an average daytime abdominal pain scoreless than or equal to 2.0 over the 2 weeks prior to randomization. 
• Patient has at least 1 daytime bowel movement with a consistency of Type 6 or Type 7 on the pediatric Bristol Stool Form Scale (p-BSFS) on at least 2 days per week during the 2 weeks prior to randomization that occurs in the absence of laxatives. 
• Patient has no clinically significant findings on a physical examination, vital sign assessment, electrocardiogram (ECG), and clinical laboratory tests (clinical chemistry panel, complete blood count, urine drug screen, urinalysis) after providing informed assent and after written consent is obtained, but before receiving the first dose of study treatment. (A central laboratory will be used to evaluate all urine [except urine pregnancy tests] and blood samples and will utilize reference ranges specific to a patient's age and gender. ECGs will be performed and electronically transmitted to a central ECG laboratory for analysis by a pediatric cardiologist in accordance with the instructions provided by the central ECG laboratory. The Investigator will determine if a particular finding is clinically significant. [In making this determination, the Investigator will consider whether the particular finding could represent a condition that would exclude the patient from the study, could represent a safety concern if the patient participates in the study, or could confound the study-specific assessments of safety or efficacy.])

• Patient has no gallbladder, (ie, agenesis of the gallbladder or cholecystectomy). 
• Patient has had any of the following surgeries:
  • Any abdominal surgery within the 3 months prior to Screening; or
  • A history of major gastric, hepatic, pancreatic, or intestinal surgery.  (Note: appendectomy, hemorrhoidectomy, or polypectomy greater than 3 months post-surgery are allowed. For the purposes of this study, laparoscopic surgeries without complication are considered minor and non-exclusionary, provided the condition for which the surgery was performed was not exclusionary.)
• Patient has a history of chronic or severe constipation or sequelae from constipation, or known or suspected mechanical GI obstruction or pseudo obstruction. 
• Patient has a history or current diagnosis of constipation with encopresis. 
• Patient meets the child/adolescent Rome IV criteria of IBS with constipation, IBS with constipation and diarrhea (mixed), unspecified IBS, or Patient has a history of intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation. 
• Patient has a documented history of hepatic impairment as defined by Child-Pugh Classification Grade A, B or C. 
• Patient has a history or current diagnosis of inflammatory or immune-mediated GI disorders including inflammatory bowel disease (ie, Crohn's disease, ulcerative colitis, microscopic colitis). 
• Patient has celiac disease, or a positive serological test for celiac disease and the condition has not been ruled out by endoscopic biopsy.
• Patient has any congenital and/or acquired malabsorption syndrome (eg, Shwachman-Diamond syndrome). 
• Patient has a history of a microbiologically documented (ie, stool culture or medical history) GI infection within 3 months prior to Screening. 
• Patient has a known lactose or fructose intolerance that is associated with diarrhea, abdominal pain or discomfort, and that could confound assessments in the study. 
• Patient has a history of diverticulitis within 3 months prior to Screening.

• Clinical diagnosis of Cerebral Cavernous Angioma (CA).
• Age 18 or older.
• Solitary or multiple.
• Familial or sporadic.
• With or without prior symptoms.

• Prior excision of a solitary CA lesion.
• Prior stereotactic radiosurgery or any brain irradiation.
• Spinal cavernoma without brain lesion.
• Other brain pathology unrelated to CA (demyelinating disease, brain tumor).
• Seizures or stroke unrelated to CA in the prior year.
• Current pregnancy or within 6 months postpartum.
• Reluctance to undergo venipuncture or donate blood specimen, or be called for clinical follow-up for up to one year.

Eligibility last updated 9/2/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 6/15/22.  Questions regarding updates should be directed to the study team contact.

• Patient is male or female and is 2 months to 24 months of age, inclusive.
• Patient has been diagnosed with IS within 6 weeks prior to Screening. Diagnostic criteria include both clinical spasms and an electroencephalogram (EEG) pattern consistent with hypsarrhythmia or significant abnormality compatible with IS.
  • NOTE: If a video EEG is performed at the clinical site within 48 hours prior to the patient's parent/guardian providing written informed consent, and it meets the criteria, this video EEG may be used as the screening/baseline EEG for the study.
• Patient has normal renal function as defined by an estimated glomerular filtration rate (eGFR).
• > 60 mL/min/1.73 m^2, calculated as eGFR = 0.413 x (height [cm]/ serum creatinine [mg/dL]).
• Patient's legally authodzed representative (i.e., parent or guardian) must provide written informed consent obtained per Institutional Review Board policy and requirements, consistent with the International Council for Harmonisation.
• Patient's parent/guardian is able to understand and willing to comply with study procedures and restrictions.

• Patient has been diagnosed with tuberous sclerosis.
• Patient has acute illness considered clinically significant by the Investigator within 30 days prior to Screening.
• Patient has a diagnosis of recent systemic fungal infection; history of ocular herpes simplex; history of or current peptic ulcer; uncontrolled hypertension or congestive heart failure; or any other condition that would be significantly impacted by the study drug.
• Patient has a preplanned surgery or procedurc(s) that would interfere with the conduct of the study.
• Patient has received any prior treatment for IS.
• Patient has been previously treated with adrenocorticotropic honnonc (ACTH), corticosteroids, or vigabatrin for seizures.
• Patient has been previously treated with a course of corticosteroids for an indication other than seizures within 30 days prior to Screening.
• Patient has a known or suspected allergy to ACTH or vigabatrin or any component of AMZ002 or vigabatrin.
• Patient has used any other investigational drug within 30 days or 5 half-lives prior to the first dose of AMZ002 or vigabatrin (whichever is longer).
• Patient's parent/guardian is unable to provide written informed consent and/or to complete the daily diary.
• Patient has any other disease, condition, or therapy that, in the opinion of the Investigator, might compromise safety or compliance, preclude the patient from successfully completing the study, or interfere with the interpretation of the results.

Eligibility last updated 9/15/21. Questions regarding updates should be directed to the study team contact.

• Adult subject, ≥ 18 years old at the time of informed consent.
• Able and willing to give informed consent and comply with all study visits and procedures.
• Presentation with macula-off RRD with a duration ≥ 24 hours up to 14 days from time of central visual decline to the Baseline (Visit 2) visit, inclusive (based on subject reported date of loss of central vision) in the Study Eye (SE).
• Visual acuity with subject's current corrective lenses or pinhole of 20/100 (line scoring) on the Snellen or ETDRS chart to light perception (LP) in the SE.
• Visual acuity with subject's current corrective lenses or pinhole of 20/200 (line scoring) or better in the fellow eye.
• Determination by Investigator of macula-off status by clinical examination with confirmation by SD-OCT or B-scan ultrasound, if available.
• SOC retinal reattachment surgery by means of a pars plana vitrectomy (with or without scleral buckle) is indicated.
• In the opinion of the Investigator, can safely undergo the IVT injection procedure at Baseline (Visit 2).
• Surgical repair scheduled or anticipated to take place >12 hours after IVT injection or sham (Visit 2) and ≤10 days from Screening (Visit 1).

• Presence of a complex retinal detachment (RD) in the SE, identified by one or more of the following:
  • Giant retinal tear, defined as retinal break ≥ 3 clock hours in extent;
  • Proliferative vitreoretinopathy grade C1 or worse on the Retina Society Terminology Committee Classification System;
  • Presence of tractional detachments as seen in proliferative retinopathies;
  • RRD in the setting of open- or closed-globe trauma;
  • RRD following endophthalmitis or infectious retinitis;
  • Similarly complex RD as determined by the Investigator.
• Use of silicone oil tamponade in the primary RD repair without planned removal by end of study.
• Vitreous hemorrhage or cataract in the SE that prohibits adequate examination for other exclusion criteria, per Investigator's discretion.
• Presence of ocular or periocular infection or intraocular inflammation in either eye.
• Uncontrolled glaucoma, as defined by an IOP > 36 mmHg in either eye, at Screening.
• Any other significant ocular disease in the SE that, in the opinion of the Investigator, would preclude a postoperative (post-op) visual acuity of at least 20/30.
• History of previous ocular surgery in the SE for RD (excluding only barrier laser), endophthalmitis, glaucoma tube shunts, trabeculectomy, or ocular trauma.
• Any systemic condition or ocular condition in either eye that, in the opinion of the Investigator, makes the subject unsuitable for treatment with an investigational agent or that would compromise the safety and tolerability of assessments in the trial.
• History of and/or active:
  • Autoimmune disease in active flare (i.e., not well controlled on current medications) with ocular involvement that, in the opinion of the Investigator, would impact ability to participate in the trial and/or alter the outcome of retinal reattachment surgery;
  • Ocular malignancy;
  • Proliferative diabetic retinopathy or diabetic macular edema or uveitis.
• Currently participating in other clinical trials or use of any other investigational drugs or devices within 12 weeks prior to Visit 1.
• Females who are pregnant or lactating, and women of childbearing potential (WOCBP) or men with female partners of childbearing potential who are not using at least one adequate contraceptive precaution (e.g., intrauterine device, oral contraceptive, barrier method, or other contraception deemed adequate by the Investigator).

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

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

• Written informed consent.
• Aged 18 or above.
• Unresectable stage III or stage IV squamous or non-squamous NSCLC not amenable to curative surgery or radiation.
• Documented PD-L1 expression by PD-L1 IHC per local report.
• Confirmed progression during treatment with a CPI-including regimen.
• ECOG performance status of 0 or 1 at enrolment.
• Life expectancy of ≥ 12 weeks at enrolment.
• Adequate bone marrow, liver and kidney function.

• Sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusion.
• Documented test result for any other known genomic alteration for which a targeted therapy is approved in first line per local standard of care (e.g. ROS1, NTRK fusions, BRAF, V600E mutation).
• Previous treatment with an anti-TIGIT therapy.
• Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.
• Primary or secondary resistance after treatment with 2 or more regimens including a CPI.
• Symptomatic central nervous system (CNS) metastasis.
• Thromboembolic event within 3 months prior to enrolment.
• Other invasive malignancy within 2 years prior to screening.

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

• Patients ≥ 18 to ≤ 80 years (at date of signing the informed consent form [ICF]), but at least of legal age in the given country.
• Biopsy confirmed diagnosis of IgAN within the past 8 years prior to signature of the ICF.
• Proteinuria at screening visit ≥ 1.0 g/d.
• Treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB) at maximum doses or maximally tolerated doses for ≥ 3 months prior to date of informed consent and adequate blood pressure (BP) control (recommended BP is < 125 mm Hg systolic and < 75 mm Hg diastolic) In case a patient is intolerant to even a very low dose of either ACEi or ARB therapy, approval for participation in the trial has to be obtained from the Medical Monitor prior to randomization.
• A female of childbearing potential (FCBP) is only eligible to participate if she is not pregnant, not breast feeding, and agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of Felzartamab.

• Secondary forms of IgAN, indicated by the presence of any other systemic disease potentially leading to IgA deposits (e.g., Lupus nephritis, Schönlein-Henoch purpura, ankylosing spondylitis, dermatitis herpetiformis, chronic liver disease, inflammatory bowel disease, celiac disease).
• Severe renal impairment as defined by estimated GFR < 30 mL/min (using chronic kidney disease-epidemiology collaboration [CKD-EPI] formula) or the need for dialysis or renal transplant.
• Rapidly progressive variant of IgAN, defined as eGFR loss by more than 30% per 3 months and not explained by changes in renin angiotensin system (RAS) blockade.
• Minimal change variant of IgAN.
• Concomitant other progressive glomerulonephritis or non-immunologic glomerular disease such as diabetic nephropathy.
• Systemic immunosuppression (e.g. mycophenolate mofetil [MMF], cyclophosphamide, biologics like rituximab [RTX]), in particular corticosteroid therapy exceeding 20 mg/day prednisone-equivalent for more than 7 consecutive days within 180 days prior to signing ICF.
• Any previous treatment with an anti-CD38 antibody.
• Body mass index (BMI) > 35 kg/m^2.
• Hemoglobin < 90 g/L.
• Thrombocytopenia: Platelets < 100.0 x 10^9 /L.
• Neutropenia: Neutrophils < 1.5 x 10^9 /L.
• Leukopenia: Leukocytes < 3.0 x 10^9 /L.
• Diabetes mellitus type 1.
• Diabetes mellitus type 2:
  • Patients with type 2 diabetes mellitus may only enter the clinical trial if a kidney biopsy performed within 6 months prior to signing ICF shows IgAN without evidence of diabetic nephropathy and their disease is controlled, such as:
    • Glycated hemoglobin (HbA1c) < 8.0% or < 64 mmoL/mol.;
    • No diabetic retinopathy known;
    • No peripheral neuropathy known.
• Significant uncontrolled cardiovascular disease (including arterial or venous thrombotic or embolic events) or cardiac insufficiency (New York Heart Association [NYHA] class IV) as judged by the investigator.
• Clinically significant findings on a 12-lead electrocardiogram (ECG) as determined by the investigator at screening.
• History of significant cerebrovascular disease or sensory or motor neuropathy of toxicity ≥ grade 3.
• Aspartate aminotransferase or alanine aminotransferase > 1.5 x ULN, alkaline phosphatase > 3.0 x ULN.
• Known or suspected hypersensitivity to Felzartamab and its excipients (L-histidine, sucrose, polysorbate 20).
• Serologic markers positive for HIV or history of HIV, hepatitis C (patients with positive anti-hepatitis C virus [anti-HCV] antibody but negative HCV RNA polymerase chain reaction [PCR] can enroll) or active or latent hepatitis B (patients with positive hepatitis B surface antigen [HBsAg] are excluded). For patients with positive hepatitis B core antibody [anti-HBc], hepatitis B virus (HBV) DNA test by PCR must be non-detectable to enroll).
• Any malignancy within 5 years prior to screening start, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or other non-melanomatous skin cancer.
• Treatment within 5 terminal half-lives (if known) or within the last 30 days prior to Visit 2, whatever is longer) with investigational drugs.
• Any active infection (viral, fungal, bacterial) requiring systemic therapy.

Eligibility last updated 1/19/22. Questions regarding updates should be directed to the study team contact.

Children under the age of 18 and adults lacking the capacity to consent will not be included in this study.

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

Inclusion Criteria

• All  who have been seen in the Long QT Syndrome Clinic at the Mayo Clinic in Rochester, MN

• Age ≥ 65 years.
• Histologically confirmed newly diagnosed Grade IV malignant glioma.
• Planned radiation treatments at Mayo Clinic Arizona or Mayo Clinic Rochester.
• Willing to sign release of information for any radiation and/or follow-up records.
• Provide informed written consent.
• Patients with eGFR ≥ 60 mg/min/1.72m^2.
• Ability to complete questionnaire(s) by themselves or with assistance.
• ECOG performance status 0, 1, 2.

• Patients diagnosed with Grades I-III glioma.
• Currently on Avastin at time of treatment.
• Unable to undergo MRI scans with contrast (e.g., cardiac pacemaker, defibrillator, kidney failure).
• Unable to undergo an 18F-DOPA-PET scan (e.g., Parkinson’s Disease, taking anti-dopaminergic, or dopamine agonist medication or less than 6 half-lives from discontinuance of dopamine agonists).
  • NOTE: Other potentially interfering drugs: amoxapine, amphetamine, benztropine, buproprion, buspirone, cocaine, mazindol, methamphetamine, methylphenidate, norephedrine, phentermine, phenylpropanolamine, selegiline, paroxetine, citalopram, and sertraline. If a patient is on any of these drugs, list which ones on the On-Study form.
• Pregnant women, nursing women, or men or women of childbearing potential who are unwilling to employ adequate contraception.
  • NOTE: All women enrolled in this study will be age 65 or over, and at the determination of the PI, will not be of childbearing potential.  If the radiology department requires a pregnancy test before administering the 18FDOPA injection, they may perform one per their standard of care.

• Admitted to a hospital with symptoms suggestive of Coronavirus Disease 2019 (COVID-19) and requires ongoing medical care.
• Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
• Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
• Male or non-pregnant female adult ≥ 18 years of age at time of enrollment.
• Illness of any duration and has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g., Nucleic Acid Amplification Test [NAAT], antigen test) in any respiratory specimen, or saliva 5 times the upper limit of normal.
• Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), mechanical ventilation or ECMO (ordinal scale category 5, 6, or 7). 
• Women of childbearing potential must agree to either abstinence or use at least one acceptable method of contraception from time of screening through 5 months post study IP dosing.
  • Note: acceptable methods include barrier contraceptives (condoms or diaphragms) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization. 
• Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID-19 through day 29. 

• ALT or AST > 5 times the upper limit of normal. 
• Subjects with a low glomerular filtration rate (eGFR), specifically:
  • Subjects with a glomerular filtration rate (eGFR) 20-30 mL/min are excluded unless in the opinion of the principal investigator (PI), the potential benefit of participation outweighs the potential risk of study participation;
  • All subjects with a glomerular filtration rate (eGFR) < 20 mL/min (including hemodialysis and hemofiltration) are excluded.
• Pregnancy or breast feeding.
• Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of enrollment.
• Allergy to any study medication.
• Received five or more doses of remdesivir prior to screening.
• Received two or more doses of > 60 mg of prednisone or equivalent in the 7 days prior to screening.
• Received small molecule tyrosine kinase inhibitors, including Janus kinase (JAK) inhibitors (e.g., baricitinib, ibrutinib, acalabrutinib, imatinib, gefitinib), in the 4 weeks prior to screening.
• Received monoclonal antibodies targeting cytokines (e.g., tumor necrosis factor (TNF) inhibitors, anti-IL-1 [e.g., anakinra, canakinumab], anti-IL-6 [e.g., tocilizumab, sarilumab, sitlukimab]), or T-cells (e.g., abatacept) in the 4 weeks prior to screening.
• Received monoclonal antibodies targeting B-cells (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening.
• Received granulocyte-macrophage colony-stimulating factor (GM-CSF) agents (e.g., sargramostim) within 2 months prior to screening.
• Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator, the risk of immunosuppression with lenzilumab is larger than the risk of Coronavirus Disease 2019 (COVID-19).
• Received any live vaccine in the 4 weeks prior to screening.
• Known active tuberculosis.
• Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV) or untreated hepatitis C (HCV) infection.
• History of pulmonary alveolar proteinosis (PAP).
• Has a malignancy currently receiving immunosuppressive chemotherapy, immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis.
• Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results.
• Positive test for influenza virus during the current illness (influenza testing is not required by protocol).
• Previous participation in an ACTIV-5/Big Effect Trial (BET).

• Subjects with DM1 which is genetically proven or clinically diagnosedFamily members of subjects with DM1 who are affected or unaffected by the disease
• Ability to understand and willingness to sign the informed consent documents
• Age ≥18 yrs

• Unable or unwilling to sign or understand the informed consent documents
• Unwilling to participate in the research
• Unwilling to allow genetic testing
• Unwilling to allow samples to be sent to other institutions for testing
• Not meeting the inclusion criteria

• Biopsy proven cutaneous mastocytosis with or without evidence of systemic disease.
• Male and female patients, 18 to 80 years of age.
• No UVB treatment of the skin for 6 months prior to study entry.
• No use of topical or systemic corticosteroids for 1 month prior to study entry.
• Good general health as confirmed by medical history.
• Female patients of child-bearing potential with negative urine pregnancy test who agree to use effective methods of birth control or remain abstinent during treatment. Participants must use birth control for the entire study and for at least 1 week after the last application of the study formulation. Acceptable methods of birth control include ongoing hormonal contraception methods, (such as birth control pills, patches, injections, vaginal ring, or implants), barrier methods (such as a condom (for men) or diaphragm used with a spermicide), intrauterine devices, tubal ligation, or abstinence.
• Patients who are willing and capable of cooperating to the extent and degree required by the protocol.
• Patients who read and sign an approved informed consent for this study.

• Vulnerable study population.
• Exposure to ultraviolet B (UVB) radiation to any region of the skin surface for 6 months.
• Regular use of skin lightening agents within 1 month of study entry, including:
  • Topical corticosteroids;
  • Topical bleaching products;
  • Topical retinoids.
• Use of systemic preparations within 1 month of study entry, including:
  • Systemic corticosteroids;
  • Systemic cyclosporine, interferon;
  • Systemic acitretin, etretinate, isoretinoin;
  • Systemic methotrexate;
  • Systemic photoallergic, phototoxic and/or photosensitizing drugs.
• UV light therapy and sunbathing.
• Inability to communicate or cooperate with the Principal Investigator and/or Investigators due to language problems, poor mental development or impaired cerebral function.
• Pregnant or nursing women.
• Women planning a pregnancy within the study period.