Gastroenterology · Clinical trials
Crohn's 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 crohn's disease — and why its trials are hard
Crohn's disease is a chronic, relapsing inflammatory bowel disease characterized by transmural, patchy inflammation that can affect any segment of the gastrointestinal tract from mouth to anus, most often the terminal ileum and colon. Symptoms include abdominal pain, chronic diarrhea, weight loss, fatigue, and complications such as strictures, fistulae, and abscesses. The therapeutic landscape has expanded from corticosteroids and immunomodulators to targeted biologics and small molecules. Anti-TNF agents (infliximab, adalimumab) were the first biologics to demonstrate durable clinical remission and mucosal healing. Subsequent mechanisms include gut-selective anti-integrin therapy (vedolizumab), interleukin-12/23 blockade (ustekinumab), selective IL-23 inhibition (risankizumab), and oral JAK1 inhibition (upadacitinib). Treatment goals have shifted toward endoscopic remission and treat-to-target strategies rather than symptom control alone. Despite this armamentarium, a substantial proportion of patients experience primary non-response or loss of response over time, and no therapy is curative, leaving surgery necessary for many. Comparative positioning and combination strategies remain active areas of research.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| infliximab (Remicade) | 1998 | Moderate-to-severe and fistulizing Crohn's disease | ACCENT I / ACCENT II | Clinical response/remission; fistula response | ACCENT I: sustained response substantially higher with scheduled infliximab vs placebo maintenance |
| adalimumab (Humira) | 2007 | Moderate-to-severe Crohn's disease | CLASSIC I / CHARM | Clinical remission (CDAI <150) | CHARM: ~36-41% in remission at week 56 vs ~12% placebo |
| vedolizumab (Entyvio) | 2014 | Moderate-to-severe Crohn's disease | GEMINI 2 / GEMINI 3 | Clinical remission (CDAI-100 response / remission) | GEMINI 2: ~39% remission at week 52 vs ~22% placebo |
| ustekinumab (Stelara) | 2016 | Moderate-to-severe Crohn's disease | UNITI-1 / UNITI-2 / IM-UNITI | Clinical response at week 6; remission at week 44 | IM-UNITI: ~53% remission at week 44 (every-8-week dosing) vs ~36% placebo |
| risankizumab (Skyrizi) | 2022 | Moderate-to-severe Crohn's disease (first specific IL-23 inhibitor) | ADVANCE / MOTIVATE (induction), FORTIFY (maintenance) | Co-primary: clinical remission (CDAI) and endoscopic response at week 12 | ADVANCE: endoscopic response ~40% (600 mg) vs ~12% placebo; significant remission gains |
| upadacitinib (Rinvoq) | 2023 | Moderate-to-severe Crohn's disease (oral JAK1 inhibitor) | U-EXCEL / U-EXCEED (induction), U-ENDURE (maintenance) | Co-primary: clinical remission and endoscopic response | U-EXCEL: clinical remission ~49.5% vs ~29.1% placebo; endoscopic response markedly higher |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in crohn's disease development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| brazikumab (anti-IL-23) — Phase 2b/3 program (INTREPID) | Development discontinued by sponsor | Program terminated for strategic/competitive reasons despite mechanistic rationale; not due to a definitive efficacy failure (unverified specifics) |
| ozanimod (S1P modulator) — YELLOWSTONE Crohn's program | Did not achieve Crohn's approval on the timeline of its ulcerative colitis indication | Crohn's efficacy/regulatory pathway less favorable than UC; details (unverified) |
Choosing the right endpoint
Primary endpoints that matter in crohn's disease trials
- Clinical remission (CDAI <150) — Crohn's Disease Activity Index remains the classic symptom-based remission threshold used across pivotal trials.
- Endoscopic response/remission (SES-CD) — Reduction in Simple Endoscopic Score for Crohn's Disease; increasingly a co-primary or key secondary endpoint reflecting mucosal healing.
- CDAI-100 response — A decrease of at least 100 points in CDAI, historically used as a responder definition in induction studies.
- Corticosteroid-free remission — Remission without ongoing steroids, a key maintenance-phase outcome reflecting durable disease control.
How iNGENū runs crohn's 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
Crohn's Disease clinical trials — FAQs
Is Crohn's disease curable with these drugs?
How do newer IL-23 inhibitors differ from anti-TNF therapy?
What is the significance of upadacitinib's approval?
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