Clinical Trials

Inclusion Criteria:

• Signed informed consent which includes compliance with the requirements (including ileocolonoscopy and MRE) and restrictions listed in the ICF and in this protocol.

• Adults, ≥18 years of age (or higher lower bound, if the legal age of consent in the jurisdiction in which the trial is taking place is higher) at the time of signing the ICF.

• 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, caused by CD, confirmed by a centrally-read SES-CD ileal narrowing score of 3.

• Present stricture(s) can be naïve or anastomotic, and will be confirmed by centrally read MRE, according to the following criteria:

  • Localized luminal narrowing (luminal diameter ≤50% relative to normal adjacent bowel) AND

  • Bowel wall thickening (≥25% relative to adjacent bowel) *Note: Two strictures within 3 cm are considered the same stricture, and a long segment with multiple areas of narrowing or multiple strictures that have inflammation between them, is counted as 1 stricture.

• Presence of (sub)obstructive symptoms, e.g., postprandial pain, bloating, or cramping, AND/OR dietary restrictions like limiting the amount or type of food, and/or food processing methods such as softening, mashing, or blending. In the investigator’s opinion, participants should have sufficient food intake, even with diet modification, over 4 weeks prior to randomization.

• Participants should be on stable anti-inflammatory background therapy for CD and agree to maintain stable background therapy for the duration of the trial.

• Not expected in the investigator’s opinion to require hospitalization, endoscopic balloon dilation, surgical resection, or optimized anti-inflammatory therapy during the first 4 weeks of the trial.

Exclusion Criteria:

• 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.

• CD-related complications:

  • 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.

  • Anal and perianal stricture.

  • Suspected or diagnosed active intra-abdominal or perianal abscess that has not been appropriately treated and abscess in relation to the stricture.

  • Toxic megacolon.

  • Blind-ending sinus could be included.

• Endoscopic balloon dilation or surgical treatment of the index small bowel stricture within the last 6 months prior to screening.

• Current or history of vasculitis or large blood vessel disorder.

• Current or history of valvulopathy, or moderate or severe heart valve function defect, including moderate or severe valve stenosis or regurgitation OR left ventricular ejection fraction <50% as assessed locally through echocardiography.

• Hereditary xanthinuria or molybdenum cofactor deficiency.

• Any other severe acute or chronic medical condition, psychiatric disorder, laboratory abnormality, or systemic or opportunistic infection that may increase the risk associated with trial participation or trial treatment administration, or may interfere with the interpretation of trial results, as determined by the investigator. • Prior exposure to ontunisertib.

• Concomitant or prior use of the following systemically administered medications:

  • JAK inhibitor from 4 weeks prior to screening.

  • Cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil from 8 weeks prior to screening.

  • Requiring continued treatment with strong or moderate inhibitors of CYP3A4 (and/or P-gp), clinically relevant inhibitors of aldehyde oxidase, or sensitive substrates for aldehyde oxidase or P-gp from 2 weeks or 5 half-lives (whichever is longer) prior to screening.

• Clinically significant abnormal vital signs, physical examination, or abnormalities at 12-lead ECG at screening or baseline, such as PR ≥220 msec, QRS ≥120 msec, prolonged QTcF >450 msec for males or >470 msec for females, or clinically significant bradycardia, ST wave changes, or bundle branch block, or any other abnormal changes on the ECG that would interfere with measurement of the QT interval.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 06/02/2026. Questions regarding updates should be directed to the study team contact.