Janus Kinase (JAK) Inhibitors to Preserve C-Peptide Production in New Onset Type 1 Diabetes (T1D)

NCT05743244 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: TN31 JAK Inhibitors
• Study Type: interventional
• Target: 78
• Locations: 3 countries
• Sites: 30

Brief 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.

Conditions

Diabetes Mellitus, Type 1

Keywords

TrialNet; T1D

Outcome Measures

Primary Outcomes (1)

• The area under the stimulated C-peptide curve (Y_AUC)

  The primary outcome of interest is the area under the stimulated C-peptide curve over the 2-hour mixed meal glucose tolerance test conducted at the 12-month visit (Y\_AUC) over the 2-hour mixed meal glucose tolerance test conducted at the 12-month visit.

  12 Months

Study Arms (3)

Abrocitinib

EXPERIMENTAL

Abrocitinib will be self-administered as 200-milligram (mg) tablet daily for 52 weeks (12 months). The final prepared product is to be labeled to protect the blind.

Drug: Abrocitinib 200 MG Oral Tablet

Ritlecitinib

EXPERIMENTAL

Ritlecitnib will be self-administered via oral administration as a 100-mg capsule daily for 52 weeks (12 months). The final prepared product is to be labeled to protect the blind.

Drug: Ritlecitinib

Placebo

PLACEBO COMPARATOR

200 mg tablet or 100 mg capsule matching either abrocitinib or ritlecitinib will be self-administered via oral administration daily for 52 weeks (12 months). The final product is to be labeled to protect the blind.

Drug: Placebo

Interventions

Abrocitinib 200 MG Oral Tablet DRUG

Abrocitinib

Also known as: CIBINQO

Abrocitinib

Ritlecitinib DRUG

Ritlecitinib

Ritlecitinib

Placebo DRUG

Placebo for Abrocitinib or Ritlecitinib

Placebo

Eligibility Criteria

• Age: 12 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 37 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 37 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

You may not qualify 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
• a. 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

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• Pfizer: collaborator

Study Sites (30)

Children's Hospital Orange County

Orange, California, 92868, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of California- San Francisco

San Francisco, California, 94143, United States

Location

Barbara Davis Center at University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06511, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of South Florida Diabetes Center

Tampa, Florida, 33612, United States

Location

Emory Children's Center

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Louisville Pediatric Endocrinology

Louisville, Kentucky, 40202, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

The Children's Mercy Hospital

Kansas City, Missouri, 64111, United States

Location

UBMD Pediatrics

Buffalo, New York, 14203, United States

Location

Columbia University-Naomi Berrie Diabetes Center

New York, New York, 10032, United States

Location

Joslin Center at SUNY Upsate

Syracuse, New York, 13210, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Benaroya Research Institute

Seattle, Washington, 98101, United States

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

Location

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

Women and Children's Hospital-Adelaide

Adelaide, South Australia, 5006, Australia

Location

The Royal Children's Hospital - Melbourne

Melbourne, Victoria, 3052, Australia

Location

3. Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Perth Children's Hospital

Nedlands, Western Australia, 6009, Australia

Location

Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

Related Links

• TrialNet

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

abrocitinib; Tablets

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The randomization method will be stratified by TrialNet study site. The participants will not be informed regarding the intervention assignment until the end of the study. The investigator and clinic personnel will also be masked as to study assignment. Laboratories performing assays for this protocol will be masked as to the identity of biological material to be studied.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Participants aged 12-35 years will be randomized 1:1:1 to receive abrocitinib, ritlecitinib, and placebo. The planned design is to enroll 26 participants in each of the 3 arms: the abrocitinib arm, the ritlecitinib arm, and the shared placebo arm. Within the shared placebo arm, participants will be randomized 1:1 to receive placebo matched to abrocitinib or placebo matched to ritlecitinib. Randomization will be stratified by the following two age categories: 12-17 years old, and 18 years or above. Within each stratum, participants will be randomized to either the abrocitinib arm, ritlecitinib arm, or the shared placebo arm using random block sizes. The total number of enrolled participants from the older age stratum (18 years or above) will be limited to 33 to replicate the age distribution in previous new-onset trials. Participants will receive 12 months of active treatment with abrocitinib, ritlecitinib, or placebo then enter a follow-up period of up to 12 months.

Study Record Dates

• First Submitted: February 3, 2023
• First Posted: February 24, 2023
• Study Start: October 19, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); AU (6); US (23)