Gastroenterology · Clinical trials
Coeliac Disease Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About coeliac disease — and why its trials are hard
Coeliac disease is a chronic, immune-mediated enteropathy triggered by dietary gluten in genetically susceptible individuals (HLA-DQ2/DQ8). Ingested gluten peptides drive an adaptive immune response causing villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis in the small intestine, producing malabsorption, diarrhea, weight loss, anemia, and extraintestinal manifestations. Diagnosis rests on serology (anti-tissue transglutaminase, anti-endomysial antibodies) and confirmatory duodenal biopsy while on a gluten-containing diet. Critically, there is no FDA-approved pharmacologic therapy for coeliac disease. The only established, effective treatment is strict lifelong adherence to a gluten-free diet, which allows mucosal healing and symptom resolution in most patients. However, the gluten-free diet is burdensome, socially limiting, and often incompletely protective against inadvertent exposure, leaving significant unmet need. Multiple drug candidates targeting gluten degradation, tight-junction permeability, immune tolerance, and transglutaminase inhibition have been tested, but pivotal trials have repeatedly failed to meet endpoints. Persistent villous atrophy despite dietary adherence (refractory coeliac disease) remains a particularly difficult clinical problem.
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in coeliac disease development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| larazotide acetate (tight-junction regulator) — Phase 3 CeD-002 (9 Meters Biopharma) | Trial discontinued in 2022 after interim analysis; failed to show benefit over placebo | Interim futility on the primary symptom endpoint; high placebo response and difficulty demonstrating added benefit atop a gluten-free diet |
| latiglutenase (ALV003, glutenase enzyme) — Phase 2 CeliAction (ALV003-1221) | Did not meet primary histologic/symptom endpoints | No significant improvement in mucosal morphometry vs placebo; large placebo effect and enrollment on gluten-free background limited detectable signal |
Choosing the right endpoint
Primary endpoints that matter in coeliac disease trials
- Villous height to crypt depth ratio (Vh:Cd) — Quantitative histologic measure of mucosal injury/healing on duodenal biopsy, a key objective endpoint in coeliac drug trials.
- Intraepithelial lymphocyte density — Marker of ongoing immune activation used alongside villous morphometry to assess mucosal response.
- Celiac Disease Patient-Reported Outcome (CeD PRO) — Symptom-based patient-reported outcome measuring gastrointestinal symptom severity, used as a primary/secondary endpoint.
- Serologic markers (anti-tTG, anti-DGP) — Antibody levels track dietary adherence and immune activity but are supportive rather than definitive efficacy endpoints.
How iNGENū runs coeliac disease trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Coeliac Disease clinical trials — FAQs
Is there any approved drug for coeliac disease?
Why have coeliac drug trials repeatedly failed?
What is refractory coeliac disease?
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