Colitis Ulcerative
Conditions
Brief summary
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.
Interventions
DRUGDupilumab
injection solution subcutaneous
DRUGPlacebo
injection solution subcutaneous
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving clinical response at Week 24 | Week 24 | Clinical response by modified Mayo score is defined as a decrease from baseline in the modified Mayo score of ≥2 points and at least a 30% reduction from baseline, and a decrease in rectal bleeding subscore of ≥1 OR an absolute rectal bleeding subscore of 0 or 1. The modified Mayo score consists of 3 subscores; a patient-reported subscore for rectal bleeding, a patient-reported subscore for stool frequency, and a Mayo endoscopic subscore. Each subscore ranges 0-3 with higher scores indicating greater disease severity. The total modified Mayo score ranges 0-9 with higher scores indicating greater disease severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants who are in clinical response at Week 52 | Week 52 | Clinical response by modified Mayo score is defined as a decrease from baseline in the modified Mayo score of ≥2 points and at least a 30% reduction from baseline, and a decrease in rectal bleeding subscore of ≥1 OR an absolute rectal bleeding subscore of 0 or 1. The modified Mayo score consists of 3 subscores; a patient-reported subscore for rectal bleeding, a patient-reported subscore for stool frequency, and a Mayo endoscopic subscore. Each subscore ranges 0-3 with higher scores indicating greater disease severity. The total modified Mayo score ranges 0-9 with higher scores indicating greater disease severity. |
| Proportion of participants who are in clinical remission at Week 24 and Week 52 | Week 24 and Week 52 | Clinical remission by modified Mayo score is defined as a modified Mayo score of ≤2 with a stool frequency score ≤1, a rectal bleeding score = 0, AND a Mayo endoscopic subscore ≤1 with absence of friability. The modified Mayo score consists of 3 subscores; a patient-reported subscore for rectal bleeding, a patient-reported subscore for stool frequency, and a Mayo endoscopic subscore. Each subscore ranges 0-3 with higher scores indicating greater disease severity. The total modified Mayo score ranges 0-9 with higher scores indicating greater disease severity. |
| Proportion of participants in symptomatic remission over time | Baseline up to Week 52 | Symptomatic remission is defined as Mayo stool frequency score = 0, or Mayo stool frequency score = 1 with a ≥1-point decrease from baseline, and Mayo rectal bleeding score = 0. |
| Proportion of participants achieving histologic-endoscopic healing at Week 24, and Week 52 | Week 24 and Week 52 | Histologic-endoscopic healing is defined by Mayo endoscopic subscore of 0 or 1 and histological healing (Geboes score \<2). Mayo endoscopic subscore ranges 0-3 with higher scores indicating greater disease severity. The Geboes Index score is a six-grade classification system for inflammation: Grade 0 - structural change only; Grade 1 -chronic inflammation; Grade 2 - lamina propria neutrophils; Grade 3 - neutrophils in epithelium; Grade 4 - crypt destruction; and Grade 5 - erosions or ulcers. |
| Proportion of participants with a Mayo endoscopic subscore of 0 or 1 without friability at Week 24, and Week 52 | Week 24 and Week 52 | The Mayo endoscopic subscore ranges 0-3 with higher scores indicating greater disease severity. |
| Proportion of participants with a Mayo endoscopic subscore of 0 at Week 24, and Week 52 | Week 24 and Week 52 | The Mayo endoscopic subscore ranges 0-3 with higher scores indicating greater disease severity. |
| Change from baseline in the partial Mayo score at Week 8, Week 24, and Week 52 | Baseline to Week 8, Week 24 and Week 52 | The partial Mayo score consists of 3 subscores; a patient-reported subscore for rectal bleeding, a patient-reported subscore for stool frequency, and a Physician's global assessment (PGA) subscore. Each subscore ranges 0-3 with higher scores indicating greater disease severity. The partial Mayo score ranges 0-9 with higher scores indicating greater disease severity. |
| Proportion of participants in clinical remission at Week 52 who are off concomitant oral corticosteroids (OCS) at least 4 weeks prior to Week 52 | Baseline up to Week 52 | Clinical remission by modified Mayo score is defined as a modified Mayo score of ≤2 with a stool frequency score ≤1, a rectal bleeding score = 0, AND a Mayo endoscopic subscore ≤1 with absence of friability. The modified Mayo score consists of 3 subscores; a patient-reported subscore for rectal bleeding, a patient-reported subscore for stool frequency, and a Mayo endoscopic subscore. Each subscore ranges 0-3 with higher scores indicating greater disease severity. The total modified Mayo score ranges 0-9 with higher scores indicating greater disease severity. |
| Proportion of participants in clinical remission at Week 52 who are off concomitant oral corticosteroids (OCS) at least 4 weeks prior to Week 52 among participants receiving OCS at baseline | Baseline up to Week 52 | Clinical remission by modified Mayo score is defined as a modified Mayo score of ≤2 with a stool frequency score ≤1, a rectal bleeding score = 0, AND a Mayo endoscopic subscore ≤1 with absence of friability. The modified Mayo score consists of 3 subscores; a patient-reported subscore for rectal bleeding, a patient-reported subscore for stool frequency, and a Mayo endoscopic subscore. Each subscore ranges 0-3 with higher scores indicating greater disease severity. The total modified Mayo score ranges 0-9 with higher scores indicating greater disease severity. |
| Change from baseline in abdominal pain assessed by Abdominal Pain Numerical Rating Scale (NRS) at Week 8, Week 24, and Week 52 | Baseline to Week 8, Week 24 and Week 52 | Abdominal pain NRS is a single item patient report outcome (PRO) tool that patients will use to report intensity of their worst abdominal pain during a daily recall period with 0 being 'no pain' and 10 being the 'worst pain imaginable'. |
| Incidence of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) | Baseline up to Week 64 | — |
| Concentration of dupilumab in serum over time. | Baseline up to Week 64 | — |
| Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab. | Baseline up to Week 64 | — |
| Change from baseline (Screening visit) in the normalized enrichment scores (NES) in type 2 inflammation transcriptome signature at Week 24 and Week 52. | Baseline to Week 24 and Week 52 | NES is a summary score of the expression of a specified set of genes defining a molecular phenotype. |
Countries
Argentina, Canada, Chile, Japan, Mexico, Puerto Rico, South Africa, South Korea, Taiwan, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Outcome results
None listed