Janus Kinase (JAK) Inhibitors to Preserve C-Peptide Production in New Onset Type 1 Diabetes (T1D)
a study on Diabetes Diabetes Type 1
Summary
- Eligibility
- for people ages 12-35 (full criteria)
- Location
- at UCSF
- Dates
- study startedcompletion around
Description
Summary
A multi-center, placebo-controlled, double blind, 1:1:1 randomized control clinical trial testing two different JAK Inhibitors abrocitnib, ritlecitinib, and placebo in subjects with recent onset Stage 3 Type 1 Diabetes within 100 days of diagnosis.
Official Title
A Phase 2 Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subtype-Selective JAK Inhibitors for Preservation of Pancreatic Β Cell Function in Newly Diagnosed Type 1 Diabetes Mellitus
Details
This study has a total sample size of 78 participants. Of that 78, 52 participants will receive active treatment, and a total of 26 participants will receive placebo. Participants will receive 12 months of active treatment with abrocitinib, ritlecitinib, or placebo with up to 12 months of additional follow-up. During the study, participants will undergo frequent assessments of their insulin production, immunologic status, overall health and well-being and diabetes care.
Keywords
Diabetes Mellitus, Type 1, TrialNet, T1D, Diabetes Mellitus, Type 1 Diabetes Mellitus, Abrocitinib, Abrocitinib 200 MG Oral Tablet, Ritlecitinib
Eligibility
You can join if…
Open to people ages 12-35
- Provide informed consent or assent as appropriate and, if < 18 years of age have a parent or legal guardian provide informed consent
- Age 12-35 years (both inclusive) at the time of signing informed consent and assent
- Diagnosis of T1D within 100 days of the baseline visit (V0).
- Positive for at least one islet cell autoantibody; Glutamate decarboxylase (GAD)65A, mIAA (if obtained within 10 days of the onset of insulin therapy), IA-2A, ICA, or ZnT8A
- Stimulated C-peptide of ≥0.2 pmol/mL measured during mixed-meal tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes
- HbA1c ≤ 10 %
- Body weight ≥ 35kg at screening
- Willing to comply with intensive diabetes management and wear a Continuous Glucose Monitoring Device (CGM)
- Participants who are Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) seronegative at screening must be CMV and/or EBV Polymerase chain reaction (PCR) negative within 30 days of randomization and may not have had signs or symptoms of a CMV and/or EBV-compatible illness lasting longer than 7 days within 30 days of the baseline visit (V0).
- Participants who are CMV and/or EBV seropositive at screening must be CMV PCR negative and/or EBV PCR <2,000 IU/mL and must have no signs or symptoms of acute infection at the time of the baseline visit (V0).
- Be up to date on recommended vaccinations based on age of participants*
- Participants are required to receive killed influenza vaccination at least 2 weeks prior to the baseline visit (V0) when vaccine for the current or upcoming flu season is available.
Enrollment must be delayed at least 4 weeks from administration of a killed vaccine other than influenza and COVID-19 and 6 weeks from a live vaccination. Live vaccinations and non-live vaccinations (other than influzena and COVID-19) should not be given while on study drug and be postponed at least 3 months after the last dose of study drug.
- If participant is female with reproductive potential, she must have a negative pregnancy test at screening and be willing to avoid pregnancy using a highly-effective contraceptive method for the duration of the study
- Males of reproductive age must use a highly-effective contraceptive method during the treatment phase and for 3 months following last dose of study drug
- For COVID-19 vaccination, all participants will be strongly encouraged to be up-to-date with COVID-19 vaccine (s) as indicated by country-specific guidelines at least 2 weeks prior to the baseline visit (V0).
You CAN'T join if...
- Current or ongoing use of non-insulin pharmaceuticals or medication that affect glycemic control or glucose homeostasis within 7 days prior to screening or any prohibited concomitant medication listed in section 4.8
- Untreated hypothyroidism or active Graves' disease
- Concurrent treatment with other immunosuppressive agents (including biologics or steroids), other than inhaled or topical glucocorticoids
- Active acute or chronic infection requiring treatment with oral antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 1 month prior to Day 0 or superficial skin infection within 1 week prior to Day 0
- Active acute or chronic infection requiring treatment with intravenous therapy (IV) within a minimum 1 month prior to Day 0
- Specific cases should be reviewed by Infectious Disease Committee prior to enrollment
- Have active signs or symptoms of acute infection at the time of the baseline visit (V0).
- Significant trauma or major surgery within 1 month of signing informed consent.
- Considered in imminent need for surgery or with elective surgery scheduled to occur during the study
- History of disseminated herpes zoster or disseminated herpes simplex or a recurrent (more than one episode of) localized, dermatomal herpes zoster
- Have evidence of prior or current tuberculosis infection as assessed by Purified Protein Derivative (PPD), interferon gamma release assay (IGRA) or by history
- Have evidence of current or past HIV or Hepatitis B infection
- Have evidence of active Hepatitis C infection
- Have current, confirmed COVID-19 infection
- Current or history of Deep vein thrombosis (DVT), Pulmonary embolism (PE), or other thromboembolic events or history of inherited coagulopathies
- First degree relative with a history of unprovoked venous thromboembolism (i.e. without known underlying cause such as trauma, surgery, immobilization, prolonged travel, pregnancy, hormone use, or plaster cast), which suggests that a participant may be at increased risk of inherited coagulation disorder
- Any present malignancies or history of malignancy, other than a successfully treated nonmelanoma skin cancer
- History of any lymphoproliferative disorder such as EBV-related lymphoproliferative disorder, history of lymphoma, history of leukemia, or signs and symptoms suggestive of current lymphatic or lymphoid disease
- Known or suspected polymorphism in the Cytochrome P450 2C19 (CYP2C19 gene, resulting in classification as a poor CYP2C19 metabolizer).
- Have renal impairment (eGFR< 60 mL/min)
- Currently on anti-platelet therapies, excluding low dose aspirin
- One or more screening laboratory values as stated
- Neutrophils < 1,500 /μL
- Lymphocytes < 800 /μL
- Platelets < 150,000 / μL
- Hemoglobin < 6.2 mmol/L (10.0 g/dL)
- Potassium > 5.5 mmol/L or <3.0 mmol/L
- Sodium > 150mmol/L or < 130mmol/L
- AST or ALT ≥ 2.5 times the upper limit of normal
- Bilirubin ≥ 1.5 times upper limit of normal unless diagnosed with Gilbert's syndrome
- LDL >160 mg/dL
- Vaccination with a live virus within the last 6 weeks and killed vaccine within 4 weeks (except 2 weeks for flu vaccine and COVID vaccine)
- Be currently pregnant or lactating or anticipate becoming pregnant during the study
- Male participants able to father children and female participants of childbearing potential who are unwilling or unable to use 2 effective methods (at least 1 highly effective method) of contraception, including abstinence, as outlined in this protocol for the duration of the study and for at least 3 months after the last dose of investigational product
- Be currently participating in another T1D treatment study
- Have hearing loss with progression over the previous 5 years, or sudden hearing loss, or middle or inner ear disease such as otitis media, cholesteatoma, Meniere's disease, labyrinthitis, or other auditory condition that is considered acute, fluctuating, or progressive
- Acute coronary syndrome (e.g., myocardial infarction, unstable angina pectoris) and any history of cerebrovascular disease within 24 weeks before screening; Heart failure NYHA (New York Heart Association) III, NYHA IV
- ANY of the following conditions at screening:
- . Screening 12-lead electrocardiogram (ECG) that demonstrates: i. Clinically significant abnormalities requiring treatment (eg, acute myocardial infarction, serious tachy- or brady-arrhythmias) or indicating serious underlying heart disease (eg, cardiomyopathy, Wolff-Parkinson- White syndrome); ii. Confirmed QT corrected using Fridericia's correction factor (QTcF) prolongation (>450 milliseconds).
- . Long QT Syndrome, a family history of Long QT Syndrome, or a history of Torsades de Pointes (TdP).
- History of chronic alcohol abuse or intravenous drug abuse or other illicit drug abuse within 2 years prior to screening
- Current or past use of tobacco or nicotine containing products more than the equivalent of 5 cigarettes per day
- Participant is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the trial
- Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk
- Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results
Locations
- University of California- San Francisco
accepting new patients
San Francisco California 94143 United States - Children's Hospital Orange County
accepting new patients
Orange California 92868 United States - Stanford University
accepting new patients
Palo Alto California 94304 United States
Details
- Status
- accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Links
- TrialNet
- ID
- NCT05743244
- Phase
- Phase 2 research study
- Study Type
- Interventional
- Participants
- Expecting 78 study participants
- Last Updated