Overview
The protocol of this Phase 2 clinical trial consists of a double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of dupilumab in participants with moderately to severely active Ulcerative Colitis (UC) with an eosinophilic phenotype.
Screening period: 2 to up to 4 weeks
Treatment period:
52-week investigational medicinal product (IMP) intervention (dupilumab or matching placebo) from Week 0 to Week 52 Open-label arm (optional): administration of open-label dupilumab therapy for study participants who qualify. Follow-up period: 12 weeks The maximum duration of study per participant is up to 68 weeks.
Eligibility
Inclusion Criteria:
- Participants must be ≥18 years of age at the time of signing the informed consent.
- Evidence of biomarker enrichment at time of screening.
- Moderately to severely active UC, defined as a baseline modified Mayo score of 5 to 9, inclusive, using the Mayo endoscopic subscore assigned during the concurrent local and central reading of the video endoscopy.
- Has a screening endoscopy with ≥2 endoscopic subscore in the Mayo score component assessment as determined by concurrent local and central reading of the video endoscopy.
- Has a baseline rectal bleeding subscore of ≥1 and baseline a stool frequency score of ≥1 as determined by the Mayo score component assessment.
- Participants with inadequate response/non-response, loss of response, or are intolerant of standard biologic therapy for their UC AND/OR Inadequate or non-responders, have shown loss of response, or are intolerant to at least 1 of the following treatments: oral corticosteroids (≤20 mg/day), 5-aminosalicylic acid (ASA) compounds, immunomodulators, small molecules.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
- Severe extensive colitis as evidenced by:
- Current hospitalization
- Likely to require surgery for the treatment of UC within 12 weeks of Screening Visit
- UC limited to the rectum only or to <20 cm of the colon as determined by central
reading.
- Presence of an ileal pouch, ostomy, stoma or fistula or history of a fistula.
- Require, or required within the 2 months before screening, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage, or other conditions possibly confounding the evaluation of benefit from study agent treatment.
- Has a prior medical history of eosinophilic colitis.
- Participants with abdominal abscess, fulminant disease, or toxic megacolon.
- Participants with intestinal failure or short bowel syndrome.
- Presence of symptomatic colonic or small bowel obstruction, confirmed by objective radiographic or endoscopic evidence of a stricture with resulting obstruction (dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy).
- History of extensive colonic resection (eg, less than 30 cm of colon remaining) that would prevent adequate evaluation of the effect of study agent on clinical disease activity.
- History of colonic mucosal dysplasia or presence of adenomatous colonic polyps not removed OR presence of colonic mucosal dysplasia or adenomatous colonic polyps not removed during colonoscopy at screening visit.
- If the participant has extensive colitis for ≥8 years or disease limited to left side of colon (ie, distal to splenic flexure) for >10 years, regardless of age, a colonoscopy within 1 year of the screening visit is required to survey for dysplasia. Participants with dysplasia or cancer identified on biopsies will be excluded.
- Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, or Crohn's disease or clinical findings suggestive of Crohn's disease.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.