A Study to Investigate the Efficacy and Safety of Dupilumab Therapy Compared With Placebo in Participants Aged ≥18 Years With Moderately to Severely Active Ulcerative Colitis With an Eosinophilic Phenotype (LIBERTY-UC SUCCEED (Study in UC for Clinical Efficacy Evaluation of Dupilumab))
Study Details
Study Description
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 4 weeks
Treatment period:
52-week investigational medicinal product (IMP) intervention (dupilumab or matching placebo) from Week 0 to Week 52 Follow-up period: 12 weeks The maximum duration of study per participant is up to 68 weeks.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dupilumab Initial loading dose followed by regular administration for the duration of the treatment period. |
Drug: Dupilumab
injection solution subcutaneous
Other Names:
|
| Placebo Comparator: Placebo Initial loading dose followed by regular administration for the duration of the treatment period. |
Drug: Placebo
injection solution subcutaneous
|
Outcome Measures
Primary Outcome Measures
- Proportion of participants who are in clinical remission at Week 24 [Week 24]
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.
Secondary Outcome Measures
- Proportion of participants achieving clinical response by modified Mayo score at Week 8, Week 24, and Week 52 [Week 8, Week 24 and 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 by modified Mayo score at Week 8 and Week 52 [Week 8 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 8, Week 24, and Week 52 [Week 8, 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 8, Week 24, and Week 52 [Week 8, 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 8, Week 24, and Week 52 [Week 8, 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 52]
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants must be ≥18 years of age at the time of signing the informed consent.
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Evidence of biomarker enrichment at time of screening.
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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.
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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.
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Has a baseline rectal bleeding subscore of ≥1 and baseline a stool frequency score of ≥1 as determined by the Mayo score component assessment.
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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:
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Severe extensive colitis as evidenced by:
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Current hospitalization
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Likely to require surgery for the treatment of UC within 12 weeks of Screening Visit
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UC limited to the rectum only or to <20 cm of the colon.
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Presence of an ileal pouch, ostomy, stoma or fistula or history of a fistula.
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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.
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Has a prior medical history of eosinophilic colitis.
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Participants with abdominal abscess, fulminant disease, or toxic megacolon.
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Participants with intestinal failure or short bowel syndrome.
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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).
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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.
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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.
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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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Wellness Clinical Research (WCR)-Site Number:8400009 | Miami Lakes | Florida | United States | 33016 |
| 2 | Javara Research-Site Number:8400008 | Charlotte | North Carolina | United States | 28287 |
Sponsors and Collaborators
- Sanofi
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ACT17746
- U1111-1278-4042