Ritlecitinib for Celiac Disease

Overseen By Maureen Leonard, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Immunosuppressants

Disqualifiers: Gluten triggered symptoms, Inflammatory GI disorder, TB, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a drug called Ritlecitinib for individuals with celiac disease, an autoimmune condition where gluten consumption damages the small intestine. The trial aims to determine if Ritlecitinib can help manage the disease while participants consume gluten. Eligible participants should have asymptomatic celiac disease, have followed a gluten-free diet for at least six months, and possess specific genetic markers associated with the condition. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on ongoing immunosuppression or treatments that might alter T cell function, you may not be eligible to participate.

Is there any evidence suggesting that Ritlecitinib is likely to be safe for humans?

Research has shown that Ritlecitinib is generally safe for people. This treatment is already approved for alopecia areata, a type of hair loss, indicating its safety. Previous studies did not find any major safety issues, and patients managed side effects without much trouble. This early-stage trial aims to assess the safety of Ritlecitinib when people with celiac disease consume gluten. So far, the treatment appears promising in terms of safety, but further studies are needed for confirmation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for celiac disease?

Unlike standard treatments for celiac disease, which primarily involve a strict gluten-free diet, Ritlecitinib offers a novel approach by directly targeting the immune response. Ritlecitinib is a Janus kinase (JAK) inhibitor, which works by interfering with the signaling pathways that lead to inflammation in response to gluten. This mechanism sets it apart from current options that don't address the underlying immune reaction. Researchers are excited about Ritlecitinib because it could provide relief from symptoms even when accidental gluten exposure occurs, offering potentially more freedom and quality of life for those with celiac disease.

What evidence suggests that Ritlecitinib might be an effective treatment for celiac disease?

Research has shown that Ritlecitinib, a medication affecting certain proteins in the immune system, may help people with celiac disease. In previous studies, Ritlecitinib quickly lowered levels of tTG-IgA, a marker indicating the body's reaction to gluten. This trial will compare Ritlecitinib with a placebo to evaluate its effectiveness in preventing gut damage and symptoms caused by gluten. Although more research is needed, these early results offer promise for those managing celiac disease. ^{1 2 3 5 6}

Who Is on the Research Team?

Alessio Fasano, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

Adults aged 18-75 with confirmed inactive celiac disease, on a gluten-free diet for at least 6 months, and positive for HLA-DQ2.5 or HLA-DQ8 can join this trial. They must not drink too much grapefruit juice, agree to contraception if applicable, avoid strenuous exercise before visits, have no recent surgeries or need for upcoming surgery, and test negative for SARS-CoV-2.

Inclusion Criteria

I agree to not do hard exercise and will stay hydrated during the study.

You should not drink more than 8 ounces of grapefruit juice per day while participating in the study.

I agree to avoid hard exercise and stay hydrated during the study.

Exclusion Criteria

You have a positive or borderline positive blood test for a certain type of antibody called IgA anti-tissue transglutaminase.

I have been diagnosed with an inflammatory bowel condition.

You have had strong or long-lasting symptoms after eating gluten.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 10g gluten + 200mg of Ritlecitinib or placebo daily for 21 days

3 weeks

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Regular monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Ritlecitinib

Trial Overview The trial is testing the safety and effectiveness of Ritlecitinib in people with celiac disease who are in remission. Participants will either receive Ritlecitinib plus gluten or a placebo plus gluten to see how well they tolerate the reintroduction of gluten into their diet.

How Is the Trial Designed?

Group I: Ritlecitinib Active Control 2 Interventions

10g gluten + 200mg of Ritlecitinib

Group II: Placebo Placebo Group 2 Interventions

10g gluten + placebo

Ritlecitinib is already approved in European Union, United States for the following indications:

Approved in European Union as Litfulo for:

• Severe alopecia areata

Approved in United States as Litfulo for:

• Severe alopecia areata

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

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

Tofacitinib, a pan-JAK inhibitor that blocks IL-15 signaling, showed promising efficacy in reversing pathological features of celiac disease in a mouse model, suggesting it could be a potential treatment for patients who do not respond to a gluten-free diet.

The study highlights the role of IL-15 in driving tissue destruction in celiac disease, indicating that targeting this cytokine may be a valuable strategy for developing new therapies for the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib, a janus kinase inhibitor demonstrates efficacy in an IL-15 transgenic mouse model that recapitulates pathologic manifestations of celiac disease. Yokoyama, S., Perera, PY., Waldmann, TA., et al.[2021]

A 14-year-old girl with refractory celiac disease (RCD) showed persistent symptoms and positive celiac-specific antibodies despite following a gluten-free diet, indicating the severity of her condition.

Treatment with infliximab led to complete serological and histological remission, demonstrating its potential efficacy in managing RCD in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission of Refractory Celiac Disease With Infliximab in a Pediatric Patient. Rawal, N., Twaddell, W., Fasano, A., et al.[2020]

Refractory celiac disease (RCD) is a serious condition where patients continue to experience symptoms despite following a strict gluten-free diet, with two types identified: Type I, which is milder, and Type II, which is associated with a severe prognosis due to its link to aggressive lymphoma.

Type II RCD is characterized by abnormal immune cell accumulation and a high risk of transforming into enteropathy-type-associated T cell lymphoma, highlighting the need for careful monitoring and potential new treatment strategies for affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refractory celiac disease: from bench to bedside. Malamut, G., Meresse, B., Cellier, C., et al.[2021]

In a study of 57 patients with refractory celiac disease (RCD) treated with open-capsule budesonide (OB), 92% showed clinical improvement and 89% showed histologic improvement, indicating its efficacy as a treatment option.

OB therapy was particularly beneficial for patients who had previously failed immunosuppressive medications, suggesting it may be a promising alternative for managing RCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Capsule Budesonide for Refractory Celiac Disease. Mukewar, SS., Sharma, A., Rubio-Tapia, A., et al.[2018]

In a study of 73 patients with refractory celiac disease (RCD), the presence of less than 50% CD3 CD8 intraepithelial lymphocytes (IELs) was identified as a significant risk factor for clinical worsening, with a hazard ratio of 4.879, indicating a fourfold increased risk despite negative celiac serologies.

Patients with both <50% CD3 CD8 IELs and monoclonal TCR gene rearrangements experienced the highest rates of clinical worsening and mortality, highlighting the importance of IEL phenotype and TCR analysis in assessing the prognosis of RCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunohistochemical and T-cell receptor gene rearrangement analyses as predictors of morbidity and mortality in refractory celiac disease. Arguelles-Grande, C., Brar, P., Green, PH., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05636293

Study Details | NCT05636293 | Double Blind, Placebo- ... The investigators are proposing a double blind, placebo-controlled trial to establish safety and efficacy of ritlecitinib to prevent gluten-induced celiac ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11903591/

Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers ... Therefore, the rapid reduction in tTG-IgA levels with ritlecitinib is quite impressive and indicates that ritlecitinb may provide beneficial ...

3. trialx.com trialx.com/5-ongoing-breakthrough-clinical-trials-advancing-celiac-disease-research/

5 Ongoing Breakthrough Clinical Trials Advancing Celiac ... The trial is evaluating Ritlecitinib, an oral medication, to see if it can prevent gut damage and symptoms when gluten is reintroduced in ...

4. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/celiacdiseaseandritlecitinib

Participants needed to advance a therapeutic treatment for ... The results of this study will help us understand whether Ritlecitinib is a viable therapeutic option for patients with celiac disease.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1359644624002381

New developments in celiac disease treatments Ritlecitinib is currently being tested in a Phase II clinical study (NCT05636293) to establish safety and efficacy to prevent gluten-induced celiac enteropathy ...

6. celiac.org celiac.org/about-celiac-disease/future-therapies-for-celiac-disease/

Future Therapies for Celiac Disease Investigators at the Massachusetts General Hospital are conducting a double-blind, placebo-controlled trial to establish the safety and efficacy of Ritlecitinib ...