Double Blind, Placebo-controlled Trial to Establish Safety and Efficacy of Ritlecitinib in Celiac Disease Patients in Remission

NCT05636293 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 2022P002248
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Subjects include: aged 18 to 75 years, inclusive, have biopsy-confirmed disease that is clinically inactive as determined by negative celiac disease (CeD) serology and histology (determined via endoscopy at time of screening), have followed a gluten-free diet (GFD) for ≥6 months as reported by the subject, and be human leukocyte antigen (HLA)-DQ2.5 and/or HLA-DQ8 positive. Study involves the following randomized intervention; 10g gluten + 200mg of Ritlecitinib or placebo

Conditions

Celiac Disease

Keywords

Celiac Disease; Gluten; Gluten Challenge; Ritlecitinib

Outcome Measures

Primary Outcomes (2)

• Change in Small Intestinal Histology based on Vh:Cd ratio

  Characterize the gluten-challenge induced changes in small intestine histology using standard for Celiac Disease histological assessments related to villus height to crypt depth ratio \[Vh:Cd\]

  Through study completion, average of 1 year.

• Patient Reported Outcome Surveys (CeD PRO survey evaluation)

  Patient Reported Outcomes (PROs) - CeD PRO evaluation of gluten challenge-triggered symptoms

  Through study completion, average of 1 year.

Secondary Outcomes (2)

• Serology

  Through study completion, average of 1 year.

• Changes in Small Intestinal Histology of intraepithelial lymphocytes (IELs)

  Through study completion, average of 1 year.

Other Outcomes (14)

• Characterize the stool microbiome pre- and -post gluten challenge.

  Through study completion, average of 1 year.

• Characterize the blood microbiome pre- and -post gluten challenge.

  Through study completion, average of 1 year.

• Characterize the intestinal microbiome pre- and -post gluten challenge.

  Through study completion, average of 1 year.

Study Arms (2)

Ritlecitinib

ACTIVE COMPARATOR

10g gluten + 200mg of Ritlecitinib

Drug: Ritlecitinib; Other: Gluten

Placebo

PLACEBO COMPARATOR

10g gluten + placebo

Drug: Placebo; Other: Gluten

Interventions

Ritlecitinib DRUG

200mg Ritlecitinib

Ritlecitinib

Placebo DRUG

Placebo

Placebo

Gluten OTHER

10g of gluten

Placebo; Ritlecitinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and/or female subjects (including Women of Childbearing Potential (WOCBP)) ≥18 years to ≤75 years of age at the time of informed consent
• Have a body mass index ≥17 to \<40 (and a body weight \>45 kg at the Screening Visit).
• Agree to make every effort to avoid pregnancy (see lifestyle outline below) from the time of signing the informed consent throughout the duration of the trial, if the subject is a woman of childbearing potential and sexually active with a non-sterilized male partner.
• Have well controlled biopsy-proven CeD, compliant with a GFD for ≥6 months preceding Screening, with resolution of CeD symptoms, normalization of CeD serology (defined as \</= 2 times the upper limit of normal), and (as determined at time of screening endoscopy) negative histology (Marsh 0, 1 or 2).
• Be HLA-DQ2.5 and/or HLA-DQ8 positive, as assessed at screening. If subjects have already been genotyped, then results from previous testing may be used in lieu of genotyping at screening.
• Must obtain negative SARS-CoV-2 test result (molecular diagnostic such as RT-PCR or RT-qPCR at the discretion of the investigator) at the screening visit and both timepoints prior to endoscopy (day 1 \&15).
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• Agree to avoid strenuous exercise during the study, especially within one week prior to the scheduled study visits and maintain adequate hydration (recommended)
• Avoid consumption of grapefruit juice exceeding 8 ounces (\~240 ml) total in a day while in the study (recommended)
• Agree to the following contraception criteria:
• Subjects who are, in the opinion of the investigator, sexually active and at risk for pregnancy with their partner(s) must agree to use 2 methods of effective contraception (at least 1 highly effective method) throughout the study and for at least 28 days after the last dose of investigational product. The investigator or his or her designee, in consultation with the subject, will confirm that the subject has selected 2 appropriate methods of contraception for the individual subject and his/her partner(s) from the list of permitted contraception methods (see below) and will confirm that the subject has been instructed in their consistent and correct use. At time points indicated in the Schedule of Activities, the investigator or designee will inform the subject of the need to use 2 methods of effective contraception (at least 1 highly effective method) consistently and correctly and document the conversation, and the subject's affirmation, in the subject's chart. In addition, the investigator or designee will instruct the subject to call immediately if 1 or both selected contraception methods are discontinued or if pregnancy is known or suspected in the subject or partner.
• Highly effective methods of contraception are those that, alone or in combination, result in a failure rate of less than 1% per year when used consistently and correctly (i.e., perfect use) and include the following:
• Implantable progestogen-only hormone contraception associated with inhibition of ovulation.
• Intrauterine device (IUD).

You may not qualify if:

• Have a history of gluten triggered acute symptoms (≤24 hours after gluten exposure), and/or severe symptoms (abdominal pain interfering with daily activities, diarrhea with \>5 stools/day), and/or prolonged symptoms (duration \>7 days).
• A history of any abdominal or pelvic surgery \<3 months before trial enrollment; prior surgery abdominal or pelvic surgery (e.g., cholecystectomy, appendectomy, and hysterectomy) are permitted if performed \>3 months before trial enrollment.
• Subjects considered in imminent need for surgery or with elective surgery scheduled to occur during the study
• Have a positive or borderline positive IgA anti-tissue transglutaminase serology at Screening (defined as \>/= 2 times the upper limit of normal).
• Have Marsh 3a-c determined by pathology at Screening Endoscopy
• A diagnosis of any other inflammatory gastrointestinal disorder
• Ongoing immunosuppression or receive any treatment within 3 months the starting of the trial that might alter T cell repertoire or phenotype.
• Has a confirmed history of a SARS-CoV-2 infection within the previous 2 months of the screening visit.
• Any history of either untreated or inadequately treated latent or active TB infection by Interferon Gamma Release Assay during screening or within 12 weeks prior to randomization, current treatment for active or latent TB infection or evidence of currently active TB by chest x-ray, residing with or frequent close contact with individual(s) with active TB.
• Positive screening for HIV, Hepatitis B, Hepatitis C.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Pfizer: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Celiac Disease

Interventions

Glutens

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Prolamins; Grain Proteins; Plant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Seed Storage Proteins

Study Officials

• Alessio Fasano, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Gastroenterology Division Chief

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: December 5, 2022
• Study Start: March 1, 2023
• Primary Completion: December 9, 2025
• Study Completion: April 9, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (1)