JAK Inhibitors for Type 1 Diabetes

Not currently recruiting at 30 trial locations

Overseen By Sandra Lord, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

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 This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two new oral treatments, abrocitinib (a JAK inhibitor) and ritlecitinib, for people with Type 1 Diabetes to determine if they manage the condition better than a placebo. It targets individuals diagnosed with Stage 3 Type 1 Diabetes within the last 100 days. Ideal participants are those newly managing Type 1 Diabetes, willing to actively manage their condition, and without other serious health issues that could interfere with the trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in diabetes care.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abrocitinib has been tested in over 3,800 patients with various conditions. The studies indicate it is generally well-tolerated, though some people experienced side effects like nausea or headaches. Notably, the FDA has already approved abrocitinib for another condition, suggesting it is generally safe.

Previous studies on ritlecitinib examined its safety in more than 340 participants. Some experienced serious side effects, such as infections or allergic reactions, but these were not common.

Both treatments have undergone sufficient testing to suggest they are generally safe for those considering joining a trial. However, individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for Type 1 Diabetes focus on managing insulin levels. However, Abrocitinib and Ritlecitinib are unique because they are JAK inhibitors, which work by targeting specific proteins involved in the immune response that leads to the destruction of insulin-producing cells. Researchers are excited about these treatments because they offer a new way to potentially modify the underlying autoimmune process, rather than just addressing symptoms. This could mean better long-term outcomes and possibly reducing the need for insulin therapy. Additionally, these treatments are administered orally, which is a more convenient option compared to the injectable insulin commonly used today.

What evidence suggests that this trial's treatments could be effective for Type 1 Diabetes?

Research has shown that ritlecitinib, one of the treatments in this trial, has been promising in early studies. It was well tolerated and effective in initial patient groups. In contrast, abrocitinib, another treatment option in this trial, has quickly relieved symptoms in conditions like atopic dermatitis by helping control the immune system. This trial is studying both treatments for their potential to help people with Type 1 Diabetes by preserving insulin production. These findings suggest possible benefits, but further research is needed to confirm their effectiveness for this specific condition. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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

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.

I have tested positive for a type of diabetes-related antibody.

Exclusion Criteria

I have no current cancers except for treated nonmelanoma skin cancer.

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

I haven't needed IV treatment for an infection in the last month.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Abrocitinib 200 MG Oral Tablet
• Placebo
• Ritlecitinib

Trial Overview

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.

How Is the Trial Designed?

Group I: Ritlecitinib Experimental Treatment 1 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: Abrocitinib Experimental Treatment 1 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: Placebo Placebo Group 1 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

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

Ritlecitinib, an oral kinase inhibitor developed by Pfizer, was approved in the USA on June 23, 2023, for treating severe alopecia areata in adults and adolescents aged 12 and older.

The drug has also received approval in Japan for intractable cases of alopecia areata and is undergoing regulatory review in the EU, UK, and China, indicating its potential as a significant treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ritlecitinib: First Approval. Blair, HA.[2023]

Tofacitinib, an oral JAK inhibitor, significantly improved response rates in patients with rheumatoid arthritis (RA) across different serotype subgroups, with notable efficacy in ACR20/50/70 responses and improvements in disease activity measures compared to placebo.

The safety profile of tofacitinib was consistent across seropositive and seronegative RA patients, with similar rates of adverse events, indicating it is a safe treatment option for diverse RA populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib. Bird, P., Hall, S., Nash, P., et al.[2020]

Tofacitinib, an oral JAK inhibitor for rheumatoid arthritis, initially increases absolute lymphocyte counts (ALCs) but these counts stabilize after about 48 months of treatment, indicating a reversible effect on lymphocyte levels.

Patients with ALCs below 500 cells/mm3 are at a higher risk for serious infections, but the study found no strong link between specific T cell counts and infection rates, suggesting that monitoring ALC alone is sufficient to assess infection risk in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Short-, Mid-, and Long-Term Effects of Tofacitinib on Lymphocytes in Patients With Rheumatoid Arthritis. van Vollenhoven, R., Lee, EB., Strengholt, S., et al.[2020]

Ritlecitinib, a selective inhibitor of JAK3 and TEC kinases, was found to be generally safe and well tolerated in participants with hepatic and renal impairments, indicating its potential for use in these populations.

Innovative statistical and in silico simulation methods were successfully used to predict that patients with renal impairment would not need dose modifications for ritlecitinib, demonstrating a new approach for generating reference data in drug studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leveraging Prior Healthy Participant Pharmacokinetic Data to Evaluate the Impact of Renal and Hepatic Impairment on Ritlecitinib Pharmacokinetics. Purohit, V., Huh, Y., Wojciechowski, J., et al.[2023]

ABT-494, a selective JAK 1 inhibitor, demonstrated favorable pharmacokinetics and safety in healthy subjects and those with rheumatoid arthritis, with mild to moderate side effects and no significant drug interactions with methotrexate.

The study involved 56 healthy participants for single dosing and 44 for multiple dosing, showing that ABT-494 had a manageable elimination half-life and dose-proportional exposure, supporting its potential for further testing in phase IIb trials for rheumatoid arthritis and Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety and Tolerability of ABT-494, a Novel Selective JAK 1 Inhibitor, in Healthy Volunteers and Subjects with Rheumatoid Arthritis. Mohamed, MF., Camp, HS., Jiang, P., et al.[2018]

Abrocitinib, an oral JAK1 inhibitor developed by Pfizer, has been approved in the UK and Japan for treating moderate-to-severe atopic dermatitis in adults and adolescents aged 12 and older.

The drug has also received a positive opinion from the European Medicines Agency and is under review in several other countries, indicating its potential as a new systemic therapy option for atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abrocitinib: First Approval. Deeks, ED., Duggan, S.[2022]

Ritlecitinib, an oral Janus kinase inhibitor, is being developed for multiple conditions including alopecia areata and rheumatoid arthritis, with data from 12 clinical trials involving healthy participants and patients collected between 2014 and 2021.

The development of a population pharmacokinetic model for ritlecitinib involved three iterations, leading to a final model that effectively addressed clinical drug development questions and informed the product label, indicating its potential efficacy and safety in various conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development. Wojciechowski, J., S Purohit, V., Huh, Y., et al.[2023]

In a phase II study involving 70 patients with rheumatoid arthritis, PF-06651600 (ritlecitinib) significantly improved disease activity compared to placebo, with a mean change in the Simplified Disease Activity Index (SDAI) score of -26.1 versus -16.8 (P < 0.001).

The treatment was generally well-tolerated, with most adverse events being mild; notably, there were no serious treatment-related adverse events or deaths reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Robinson, MF., Damjanov, N., Stamenkovic, B., et al.[2021]

Tofacitinib significantly reduced the flare rate in patients with polyarticular course juvenile idiopathic arthritis (JIA), with only 29% of patients on tofacitinib experiencing flares compared to 53% on placebo, indicating its efficacy as a treatment.

The safety profile of tofacitinib was comparable to placebo, with serious adverse events occurring in only 1% of patients on tofacitinib and no deaths reported, suggesting it is a safe option for young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial. Ruperto, N., Brunner, HI., Synoverska, O., et al.[2022]

Tofacitinib at doses of 3 mg or higher taken twice daily showed significant efficacy in treating active rheumatoid arthritis, with ACR20 response rates reaching up to 71.9% by week 12, compared to 22.0% for placebo.

The treatment was generally well-tolerated, with manageable side effects, the most common being urinary tract infections and diarrhea, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Fleischmann, R., Cutolo, M., Genovese, MC., et al.[2022]

In a phase 2 trial involving 91 patients with recent-onset type 1 diabetes, baricitinib treatment for 48 weeks significantly preserved β-cell function, as indicated by higher C-peptide levels compared to placebo (0.65 vs 0.43 nmol per liter per minute).

Baricitinib also reduced the mean daily insulin dose required by patients, demonstrating its potential efficacy in managing type 1 diabetes without increasing the frequency or severity of adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib and β-Cell Function in Patients with New-Onset Type 1 Diabetes. Waibel, M., Wentworth, JM., So, M., et al.[2023]

JAK inhibitors are a new class of oral medications that effectively treat autoimmune and autoinflammatory diseases, showing anti-rheumatic effects similar to biologic drugs.

While JAK inhibitors offer convenient administration and strong efficacy, they also come with specific side effects that are common across the class, highlighting the need for careful monitoring in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diagnosis and treatment of rheumatoid arthritis:toward the best practice. Best practice with JAK inhibitors.] Yamaoka, K.[2019]

In a Phase 3 trial involving 797 patients with rheumatoid arthritis who did not respond adequately to methotrexate, tofacitinib (5 or 10 mg twice daily) led to significant improvements in patient-reported outcomes (PROs) after 3 months, which were maintained over 24 months.

Patients receiving tofacitinib reported clinically meaningful enhancements in various aspects of health, including pain and quality of life, compared to those on placebo, with similar improvements observed in patients who switched from placebo to tofacitinib later in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib in combination with methotrexate in patients with rheumatoid arthritis: patient-reported outcomes from the 24-month Phase 3 ORAL Scan study. Strand, V., van der Heijde, D., Tanaka, Y., et al.[2022]

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Cibinqo (abrocitinib) News

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Cibinqo, INN-abrocitinib - EMA

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CIBINQO (abrocitinib) - accessdata.fda.gov

The safety of CIBINQO was evaluated in four randomized, placebo-controlled clinical trials (2 monotherapy,. 1 combination therapy with topical corticosteroid, ...