Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Massachusetts General Hospital
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing Ritlecitinib to see if it can help adults with celiac disease in remission avoid symptoms when they eat gluten. Participants will take either the drug or a non-active substance and eat a small amount of gluten regularly. The drug aims to block immune signals that cause inflammation.
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.
How does the drug Ritlecitinib differ from other treatments for celiac disease?
Ritlecitinib is unique because it targets the Janus kinase (JAK) pathway, which is involved in the immune response that causes damage in celiac disease. This approach is different from the standard gluten-free diet and other treatments that do not specifically target this pathway.
12345Eligibility Criteria
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 have celiac disease, follow a strict gluten-free diet for 6+ months, and my tests show improvement.
My BMI is between 17 and 40, and I weigh more than 45 kg.
I have celiac disease, follow a strict gluten-free diet for 6+ months, and my tests show improvement.
I agree to prevent pregnancy during the trial.
I am positive for HLA-DQ2.5 or HLA-DQ8.
I am between 18 and 75 years old.
I am positive for HLA-DQ2.5 or HLA-DQ8.
Exclusion Criteria
I have been diagnosed with an inflammatory bowel condition.
I have not had any abdominal or pelvic surgery in the last 3 months.
I need surgery soon or have it scheduled during the study period.
Participant Groups
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.
2Treatment groups
Active Control
Placebo Group
Group I: RitlecitinibActive Control2 Interventions
10g gluten + 200mg of Ritlecitinib
Group II: PlaceboPlacebo Group2 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
Loading ...
Who is running the clinical trial?
Massachusetts General HospitalLead Sponsor
PfizerIndustry Sponsor
References
Tofacitinib, a janus kinase inhibitor demonstrates efficacy in an IL-15 transgenic mouse model that recapitulates pathologic manifestations of celiac disease. [2021]Celiac disease (CD) is an immune-mediated, inflammatory disorder of the small intestines with a defined genetic etiological component associated with the expression of HLA-DQ2 and/or HLA-DQ8 haplotypes. The dietary consumption of gluten-rich cereals triggers a gluten-specific immune response in genetically susceptible individuals leading to a spectrum of clinical manifestations ranging from an inapparent subclinical disease, to overt enteropathy that can in some individuals progress to enteropathy-associated T cell lymphoma (EATL). The tissue-destructive pathologic process of CD is driven by activated NK-like intraepithelial CD8(+) lymphocytes and the proinflammatory cytokine IL-15 has emerged to be pivotal in orchestrating this perpetual tissue destruction and inflammation. Moreover, transgenic mice that over-express human IL-15 from an enterocyte-specific promoter (T3(b)-hIL-15 Tg) recapitulate many of the disease-defining T and B cell-mediated pathologic features of CD, further supporting the evolving consensus that IL-15 represents a valuable target in devising therapeutic interventions against the form of the disease that is especially refractory to gluten-free diet. In the present study, we evaluated the potential efficacy of tofacitinib, a pan-JAK inhibitor that abrogates IL-15 signaling, as a therapeutic modality against CD using T3(b)-hIL-15 Tg mice. We demonstrate that tofacitinib therapy leads to a lasting reversal of pathologic manifestations in the treated mice, thereby highlighting the potential value of tofacitininb as a therapeutic modality against refractory CD for which no effective therapy exists currently. Additionally, the visceral adiposity observed in the tofacitinib-treated mice underscores the importance of continued evaluation of the drug's impact on the lipid metabolism.
Remission of Refractory Celiac Disease With Infliximab in a Pediatric Patient. [2020]Refractory celiac disease (RCD) is a rare but life-threatening complication of celiac disease (CD), and only 1 pediatric case has been reported. We report a case of a 14-year-old girl with CD presenting with persistent symptoms and positive tissue celiac-specific antibodies despite a gluten-free diet. Push enteroscopy showed jejunal scalloping and partial villous atrophy on histology. She was diagnosed with RCD and treated with infliximab with subsequent complete serological and histological remission.
Open-Capsule Budesonide for Refractory Celiac Disease. [2018]Refractory celiac disease (RCD) is a rare condition often associated with poor prognosis. Various immunosuppressive medications (IMs) have been used with modest success. We describe outcomes in patients treated with open-capsule budesonide (OB), including those for whom IM treatment failed.
Immunohistochemical and T-cell receptor gene rearrangement analyses as predictors of morbidity and mortality in refractory celiac disease. [2017]Classification of refractory celiac disease (RCD) is based on the presence or absence of monoclonal expansions of intraepithelial lymphocytes (IELs) with an aberrant immunophenotype.
Refractory celiac disease: from bench to bedside. [2021]Refractory celiac disease is defined by the persistence of symptoms of malnutrition and intestinal villous atrophy for more than 6-12 months despite strict gluten-free diet in celiac patients. Diagnosis of this rare condition is made after excluding other causes of chronic small intestinal inflammation and villous atrophy and inadvertent intake of gluten. Over the past 15 years, multidisciplinary approaches have been developed to assess the mechanism of resistance to the diet, and two distinct entities have been delineated. Type II refractory celiac disease (RCD) can be defined as a low-grade intraepithelial lymphoma. RCD II is characterised by a massive accumulation of abnormal IEL that display an aberrant hybrid NK/T cell phenotype, contain clonal T cell rearrangement(s) and can mediate a cytolytic attack of the gut epithelium. This condition has a severe prognosis, largely due to the frequent transformation of RCDII IEL into overt aggressive enteropathy-type-associated T cell lymphoma. In contrast, in type I RCD, intestinal lymphocytes have a normal phenotype, and this generally milder condition remains often difficult to differentiate from uncomplicated CD except for the resistance to gluten-free diet (GFD). Several mechanisms may underlie resistance to gluten. Herein, we review the distinctive characteristics of RCD I and RCD II, the mechanisms underlying the onset of resistance to GFD, the risk of developing high grade lymphoma and possible clues to improve their treatment.