Many patients with Crohn's disease (CD) develop fibrotic narrowing (strictures) in their bowel, causing obstructive symptoms such as abdominal pain, cramping, or vomiting after meals. Because of these symptoms, patients often require bowel resection surgery. The objective of this clinical trial is to evaluate the efficacy, safety, and dose-response relationship of ontunisertib in participants with CD and symptomatic strictures, and contribute to the validation of novel endpoints to assess potential treatment benefit in patients with fibrostenosing Crohn's disease (FSCD).
The participants will be in the trial for a duration of up to 60 weeks, consisting of a 6-week screening period (with 2 screening visits), a 52-week treatment period, and a 2-week follow-up period. The visit frequency in the treatment period will be every 6 to 8 weeks.
Diagnosis of ileal or ileocolonic CD based on clinical and endoscopic or radiological evidence established at least 12 weeks prior to signing the ICF.
Presence of at least 1 endoscopically non-passable ileal stricture.
Present stricture(s) can be naïve or anastomotic, and will be confirmed by centrally read MRE.
Presence of (sub)obstructive symptoms AND/OR dietary restrictions like limiting the amount or type of food, and/or food processing methods.
History or current diagnosis of ulcerative colitis, indeterminate colitis, ischemic colitis, nonsteroidal anti-inflammatory drug-induced colitis, idiopathic colitis (i.e., colitis not consistent with CD), radiation colitis, microscopic colitis, colonic mucosal dysplasia, untreated bile acid malabsorption, or infectious colitis.
Short bowel syndrome (<200 cm small bowel remaining).
Ileostomy (diverting or end), colostomy, small bowel stoma, or ileoanal pouch.
Internal fistulae and sinus tracts deriving from the area of stenosis. Participants with perianal fistulae could be included if not septic.
Parallel
Ontunisertib
DrugOral capsule
Ontunisertib
DrugOral capsule
Ontunisertib
DrugOral capsule
Placebo
DrugMatching oral capsule
Proportion of participants achieving endoscopic passability of the ileal index stricture
To evaluate the efficacy and dose-response relationship of multiple doses of ontunisertib
Proportion of participants achieving endoscopic passability of the ileal index stricture
To evaluate the efficacy of ontunisertib in participants with FSCD, compared to placebo
Change in reliable MRE imaging features (stricture length, bowel wall thickness, prestenotic dilatation diameter) of the index stricture
To evaluate the efficacy of ontunisertib in participants with FSCD, compared to placebo
Change in total SES-CD (range, 0-56 points) (Reference: https://www.giejournal.org/article/S0016-5107(04)01878-4/abstract)
To evaluate the efficacy of ontunisertib in participants with FSCD, compared to placebo
Proportion of participants with an endoscopic response (≥50% decrease in total SES-CD) and remission (SES-CD ≤4 with no item >1)
To evaluate the efficacy of ontunisertib in participants with FSCD, compared to placebo
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