A clinical trial to assess the efficacy and safety of ontunisertib compared to placebo in patients with fibrostenosing Crohn’s disease

Prior treatment

• 01 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.
• 03 Endoscopic balloon dilation or surgical treatment of the index small bowel stricture within the last 6 months prior to screening.

Other illness

• 02 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; or Blind-ending sinus could be included.

Lab values

• 04 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.
• 05 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.
• 06 Clinically significant abnormal lab values (hematologic, liver function tests) 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.

• 01 Diagnosis of ileal or ileocolonic CD based on clinical and endoscopic or radiological evidence established at least 12 weeks prior to signing the ICF.
• 02 Presence of at least 1 endoscopically non-passable ileal stricture.
• 03 Present stricture(s) can be naïve or anastomotic, and will be confirmed by centrally read MRE.
• 04 Presence of (sub)obstructive symptoms, AND/OR dietary restrictions like limiting the amount or type of food, and/or food processing methods.
• 05 Participants should be on stable anti-inflammatory background therapy for CD and agree to maintain stable background therapy for the duration of the trial.
• 06 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.
• 07 Participants should have a body mass index ≥18 kg/m2 and <35 kg/m2.