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

Launched by MASSACHUSETTS GENERAL HOSPITAL · Nov 23, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a medication called Ritlecitinib to see if it is safe and effective for people with celiac disease who are currently not showing symptoms. Celiac disease is a condition where the body reacts negatively to gluten, a protein found in wheat, barley, and rye. Participants in the trial must be between 18 and 75 years old, have been on a strict gluten-free diet for at least six months, and have confirmed their celiac disease through a biopsy that shows no active symptoms.

Eligible participants will be randomly assigned to receive either Ritlecitinib or a placebo (a dummy treatment) after consuming a small amount of gluten. Throughout the study, participants will have regular check-ins and tests to monitor their health and response to the medication. It's important to note that women who can become pregnant must use two forms of birth control during the trial. Overall, this study aims to explore a new treatment option for managing celiac disease while ensuring that participants are closely monitored for their safety.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Male and/or female subjects (including Women of Childbearing Potential (WOCBP)) ≥18 years to ≤75 years of age at the time of informed consent
• • 2. Have a body mass index ≥17 to \<40 (and a body weight \>45 kg at the Screening Visit).
• • 3. 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.
• • 4. 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).
• • 5. 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.
• • 6. 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).
• • 7. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• • 8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• • 9. Agree to avoid strenuous exercise during the study, especially within one week prior to the scheduled study visits and maintain adequate hydration (recommended)
• • 10. Avoid consumption of grapefruit juice exceeding 8 ounces (\~240 ml) total in a day while in the study (recommended)
• 11. 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).
• • Intrauterine hormone-releasing system (IUS).
• • Bilateral tubal occlusion or tubal ligation.
• • Vasectomized partner: Vasectomized partner is a highly effective contraceptive method provided that the partner is the sole sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used. The spermatogenesis cycle is approximately 90 days
• • Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral; intravaginal; transdermal
• • Progestogen-only hormone contraception associated with inhibition of ovulation: oral; injectable.
• • Sexual abstinence: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study intervention. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
• • Male condom or female condom: All sexually active male subjects must agree to prevent potential transfer to and exposure of partner(s) to drug through ejaculate by using a condom consistently and correctly, beginning with the first dose of investigational product and continuing for at least 28 days after the last dose of investigational product. Male subjects must refrain from donating sperm during the study and for 90 days after the last dose of investigational product.
• Exclusion Criteria:
• • 1. 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).
• • 2. 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.
• • 3. Subjects considered in imminent need for surgery or with elective surgery scheduled to occur during the study
• • 4. Have a positive or borderline positive IgA anti-tissue transglutaminase serology at Screening (defined as \>/= 2 times the upper limit of normal).
• • 5. Have Marsh 3a-c determined by pathology at Screening Endoscopy
• • 6. A diagnosis of any other inflammatory gastrointestinal disorder
• • 7. Ongoing immunosuppression or receive any treatment within 3 months the starting of the trial that might alter T cell repertoire or phenotype.
• • 8. Has a confirmed history of a SARS-CoV-2 infection within the previous 2 months of the screening visit.
• • 9. 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.
• • 10. Positive screening for HIV, Hepatitis B, Hepatitis C.

Trial Officials