JAK Inhibitors for Type 1 Diabetes
Recruiting in Palo Alto (17 mi)
+20 other locations
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Must not be taking: Immunosuppressants, Biologics, Steroids, others
Disqualifiers: Infections, Cancer, Heart disease, others
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing two medications, abrocitinib and ritlecitinib, which aim to reduce immune system activity. The study focuses on people who have been recently diagnosed with Stage 3 Type 1 Diabetes. These medications work by calming the immune system to prevent it from attacking insulin-producing cells in the pancreas.
Will I have to stop taking my current medications?
The trial requires that you stop using non-insulin medications that affect blood sugar control within 7 days before screening. Additionally, you cannot be on other immunosuppressive drugs, except for certain inhaled or topical treatments.
What data supports the effectiveness of JAK inhibitors like Abrocitinib for treating Type 1 Diabetes?
JAK inhibitors, such as baricitinib, have been shown to be effective in treating several autoimmune diseases by blocking cytokine signaling, although their specific effect on preserving β-cell function in Type 1 Diabetes is still unclear.
12345Is there safety data available for JAK inhibitors like Abrocitinib and Ritlecitinib?
Abrocitinib has been approved for treating atopic dermatitis in several countries, indicating it has been evaluated for safety in humans. Ritlecitinib has been generally safe and well-tolerated in studies for various conditions, including rheumatoid arthritis and alopecia areata.
678910How is the drug Abrocitinib different from other treatments for type 1 diabetes?
Abrocitinib is a JAK inhibitor, which means it works by blocking certain enzymes (proteins) involved in the immune response, potentially offering a new way to manage autoimmune conditions like type 1 diabetes. Unlike traditional treatments that focus on insulin management, JAK inhibitors target the underlying immune processes, which could help preserve insulin-producing cells.
24111213Eligibility Criteria
This trial is for people aged 12-35 with recent Type 1 Diabetes diagnosis. They must have a certain level of C-peptide, weigh at least 35kg, be vaccinated against COVID-19 and other diseases, not pregnant or planning to become so, and willing to use contraception. Exclusions include current participation in another T1D study, certain medical conditions like heart disease or infections, drug abuse history, and specific medication use.Inclusion Criteria
Provide informed consent or assent as appropriate and, if < 18 years of age have a parent or legal guardian provide informed consent
I am up to date on my vaccinations, including the flu shot received at least 2 weeks before my first visit.
I am fully vaccinated for COVID-19, including all eligible boosters.
+10 more
Exclusion Criteria
I have no current cancers except for treated nonmelanoma skin cancer.
I haven't needed IV treatment for an infection in the last month.
You have HIV or Hepatitis B infection now or had it in the past.
+29 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive daily oral administration of either abrocitinib, ritlecitinib, or placebo for 12 months
52 weeks
Frequent assessments of insulin production, immunologic status, overall health, and diabetes care
Follow-up
Participants are monitored for safety and effectiveness after treatment
up to 12 months
Participant Groups
The trial tests two JAK Inhibitors—Abrocitinib and Ritlecitinib—against a placebo in newly diagnosed Type 1 Diabetes patients. It's randomized and double-blind meaning neither the participants nor the researchers know who gets which treatment until after the results are collected.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: RitlecitinibExperimental Treatment1 Intervention
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.
Group II: AbrocitinibExperimental Treatment1 Intervention
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.
Group III: PlaceboPlacebo Group1 Intervention
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.
Abrocitinib 200 MG Oral Tablet is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Cibinqo for:
- Moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy
🇺🇸 Approved in United States as Cibinqo for:
- Refractory, moderate-to-severe atopic dermatitis in patients twelve years of age and older whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Stanford UniversityPalo Alto, CA
University of South Florida Diabetes CenterTampa, FL
Columbia University-Naomi Berrie Diabetes CenterNew York, NY
Vanderbilt University Medical CenterNashville, TN
More Trial Locations
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Who Is Running the Clinical Trial?
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Lead Sponsor
PfizerIndustry Sponsor
References
Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial. [2022]Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA).
Baricitinib and β-Cell Function in Patients with New-Onset Type 1 Diabetes. [2023]Janus kinase (JAK) inhibitors, including baricitinib, block cytokine signaling and are effective disease-modifying treatments for several autoimmune diseases. Whether baricitinib preserves β-cell function in type 1 diabetes is unclear.
Tofacitinib in combination with methotrexate in patients with rheumatoid arthritis: patient-reported outcomes from the 24-month Phase 3 ORAL Scan study. [2022]Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we present data from the completed Phase 3 randomised controlled trial (RCT) ORAL Scan (NCT00847613), which evaluated the impact of tofacitinib on patient-reported outcomes (PROs) through 24 months in patients with active RA and inadequate responses to methotrexate (MTX-IR).
Pharmacokinetics, Safety and Tolerability of ABT-494, a Novel Selective JAK 1 Inhibitor, in Healthy Volunteers and Subjects with Rheumatoid Arthritis. [2018]ABT-494 is a potent and selective Janus kinase (JAK) 1 inhibitor being developed for the treatment of several autoimmune disorders, with potential for an improved safety profile compared with non-selective JAK inhibitors. This work characterized the pharmacokinetics, safety, and tolerability of ABT-494 following single and multiple dosing of the immediate-release formulation.
Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. [2022]To compare the efficacy, safety, and tolerability of 5 doses of oral tofacitinib (CP-690,550) or adalimumab monotherapy with placebo for the treatment of active rheumatoid arthritis (RA) in patients with an inadequate response to disease-modifying antirheumatic drugs.
Abrocitinib: First Approval. [2022]Abrocitinib (Cibinqo®) is an oral small-molecule inhibitor of Janus kinase 1 (JAK1) being developed by Pfizer for the treatment of moderate-to-severe atopic dermatitis (AD). In September 2021, abrocitinib was approved in the UK and Japan for the treatment of moderate-to-severe AD in adults and adolescents 12 years and older who are candidates for systemic therapy. Abrocitinib has also received a positive CHMP opinion in the EU for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy. Regulatory applications for the drug have also been submitted for review to several other countries, including the USA and Australia. This article summarizes the milestones in the development of abrocitinib leading to this first approval for the treatment of moderate-to-severe AD.
Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development. [2023]Ritlecitinib is an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family inhibitor undergoing parallel clinical development for alopecia areata, vitiligo, ulcerative colitis, Crohn's disease, and rheumatoid arthritis.
Leveraging Prior Healthy Participant Pharmacokinetic Data to Evaluate the Impact of Renal and Hepatic Impairment on Ritlecitinib Pharmacokinetics. [2023]Ritlecitinib is a selective, covalent, irreversible inhibitor of Janus kinase 3 (JAK3) and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinases. Pharmacokinetics and safety of ritlecitinib in participants with hepatic (Study 1) or renal (Study 2) impairment were to be characterized from two phase I studies. Due to a study pause caused by the COVID-19 pandemic, the study 2 healthy participant (HP) cohort was not recruited; however, the demography of the severe renal impairment cohort closely matched the study 1 HP cohort. We present results from each study and two innovative approaches to utilizing available HP data as reference data for study 2: a statistical approach using analysis of variance and an in silico simulation of an HP cohort created using a population pharmacokinetics (POPPK) model derived from several ritlecitinib studies. For study 1, the observed area under the curve for 24-h dosing interval and maximum plasma concentration for HPs and their observed geometric mean ratios (participants with moderate hepatic impairment vs HPs) were within 90% prediction intervals from the POPPK simulation-based approach, thereby validating the latter approach. When applied to study 2, both the statistical and POPPK simulation approaches demonstrated that patients with renal impairment would not require ritlecitinib dose modification. In both phase I studies, ritlecitinib was generally safe and well tolerated. These analyses represent a new methodology for generating reference HP cohorts in special population studies for drugs in development with well-characterized pharmacokinetics in HPs and adequate POPPK models. TRIAL REGISTRATION: ClinicalTrials.gov NCT04037865 , NCT04016077 , NCT02309827 , NCT02684760 , and NCT02969044 .
Efficacy and Safety of PF-06651600 (Ritlecitinib), a Novel JAK3/TEC Inhibitor, in Patients With Moderate-to-Severe Rheumatoid Arthritis and an Inadequate Response to Methotrexate. [2021]To evaluate the efficacy and safety of PF-06651600 (ritlecitinib), an irreversible inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, in comparison with placebo in patients with rheumatoid arthritis (RA).
Ritlecitinib: First Approval. [2023]Ritlecitinib (LITFULO™), an orally administered kinase inhibitor, is being developed by Pfizer for the treatment of alopecia areata, vitiligo, ulcerative colitis and Crohn's disease. On 23 June 2023, ritlecitinib received approval in the USA for the treatment of severe alopecia areata in adults and adolescents 12 years and older. Ritlecitinib was approved in Japan on 26 June 2023 for the treatment of alopecia areata (limited to intractable cases involving widespread hair loss). Ritlecitinib has also received a positive opinion in the EU and is under regulatory review in the UK and China. This article summarizes the milestones in the development of ritlecitinib leading to this first approval for severe alopecia areata.
[Diagnosis and treatment of rheumatoid arthritis:toward the best practice. Best practice with JAK inhibitors.] [2019]Janus kinase(JAK)inhibitor is a new orally available disease modifying anti-rheumatic drug that has shown anti-rheumatic effect resembling biologics. Clinical trials for autoinflammatory and autoimmune diseases are under investigation. Administration route is convenient compared to biologics and possess high anti-rheumatic effect, however specific side effects considered as a class-effect exists. I would like to offer the best conceivable practice with JAK inhibitors based on evidence from clinical trials and real world experiences.
Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib. [2020]Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We examined response to tofacitinib 5 or 10 mg two times a day in patients with seropositive vs seronegative RA.
Evaluation of the Short-, Mid-, and Long-Term Effects of Tofacitinib on Lymphocytes in Patients With Rheumatoid Arthritis. [2020]Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Altered lymphocyte cell counts and a potential association with increased infection rates have been reported in RA patients treated with JAK inhibitors. This analysis was undertaken to evaluate the short-, mid-, and long-term effects of tofacitinib on lymphocytes and infection rates in patients with RA.