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))

Colitis Ulcerative Clinical Trial

Official title:

A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Parallel-group Study to Evaluate the Efficacy and Safety of Dupilumab Therapy in Patients With Moderately to Severely Active Ulcerative Colitis With an Eosinophilic Phenotype

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05731128
• Other study ID #: ACT17746
• Secondary ID: U1111-1278-4042
• Status: Recruiting
• Phase: Phase 2
• Start date: January 12, 2023
• Est. completion date: February 20, 2026

Study information

• Verified date: June 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free number for US &
• Phone: 800-633-1610
• Email: contact-us[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: February 20, 2026
• Est. primary completion date: May 16, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Colitis
• Colitis Ulcerative
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• Dupilumab
injection solution subcutaneous
• Placebo
injection solution subcutaneous

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320002	Caba	Ciudad De Buenos Aires
Argentina	Investigational Site Number : 0320006	Mar del Plata
Argentina	Investigational Site Number : 0320003	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320001	San Miguel de Tucuman
Argentina	Investigational Site Number : 0320004	San Miguel de Tucumán	Tucumán
Canada	Investigational Site Number : 1240003	Montreal
Canada	Investigational Site Number : 1240006	Montreal	Quebec
Chile	Investigational Site Number : 1520001	Concepcion	Biobío
Chile	Investigational Site Number : 1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520003	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520005	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520006	Santiago
Japan	Investigational Site Number : 3920004	Bunkyo-ku	Tokyo
Japan	Investigational Site Number : 3920011	Kamakura-shi
Japan	Investigational Site Number : 3920005	Kashiwa-shi
Japan	Investigational Site Number : 3920008	Kitakyushu-shi	Fukuoka
Japan	Investigational Site Number : 3920007	Kyoto-shi	Kyoto
Japan	Investigational Site Number : 3920006	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920009	Saitama-shi
Japan	Investigational Site Number : 3920001	Sapporo-shi
Japan	Investigational Site Number : 3920002	Sapporo-shi
Japan	Investigational Site Number : 3920010	Sunto-gun	Shizuoka
Korea, Republic of	Investigational Site Number : 4100003	Busan	Busan-gwangyeoksi
Korea, Republic of	Investigational Site Number : 4100004	Daegu	Daegu-gwangyeoksi
Korea, Republic of	Investigational Site Number : 4100005	Daegu
Korea, Republic of	Investigational Site Number : 4100006	Daejeon
Korea, Republic of	Investigational Site Number : 4100002	Wonju	Gangwon-do
Mexico	Investigational Site Number : 4840004	Cdmx	Ciudad De Mexico
Mexico	Investigational Site Number : 4840003	Chihuahua
Mexico	Investigational Site Number : 4840007	Guadalajara	Jalisco
Mexico	Investigational Site Number : 4840005	Saltillo	Coahuila De Zaragoza
Mexico	Investigational Site Number : 4840002	Torreon	Coahuila De Zaragoza
Puerto Rico	Gastroenterology Research Unit, UPR Medical Sciences Campus Site Number : 6300002	San Juan
South Africa	Investigational Site Number : 7100002	Cape Town
South Africa	Investigational Site Number : 7100005	Cape Town
South Africa	Investigational Site Number : 7100007	Cape Town
South Africa	Investigational Site Number : 7100009	Cape Town
South Africa	Investigational Site Number : 7100001	Johannesburg
South Africa	Investigational Site Number : 7100006	Johannesburg
South Africa	Investigational Site Number : 7100008	Kempton Park
South Africa	Investigational Site Number : 7100003	Port Elizabeth
South Africa	Investigational Site Number : 7100004	Pretoria
Taiwan	Investigational Site Number : 1580002	Taichung
Turkey	Investigational Site Number : 7920002	Ankara
Turkey	Investigational Site Number : 7920003	Gaziantep
Turkey	Investigational Site Number : 7920005	Istanbul
Turkey	Investigational Site Number : 7920001	Mersin
Turkey	Investigational Site Number : 7920006	Zonguldak
United States	Om Research Site Number : 8400029	Apple Valley	California
United States	Washington Gastroenterology Site Number : 8400025	Bellevue	Washington
United States	Om Research Site Number : 8400028	Camarillo	California
United States	Javara Research Site Number : 8400008	Charlotte	North Carolina
United States	Gastro Center of Maryland Site Number : 8400021	Columbia	Maryland
United States	Gastroenterology Associates, P.A. Site Number : 8400012	Greenville	South Carolina
United States	Smart Medical Research Inc Site Number : 8400037	Jackson Heights	New York
United States	Katy Integrative Gastroenterology Site Number : 8400027	Katy	Texas
United States	TLC Clinical Research Inc Site Number : 8400020	Los Angeles	California
United States	Care Access Research, Lumberton Site Number : 8400018	Lumberton	North Carolina
United States	Gastroenterology Associates, PC Site Number : 8400032	Manassas	Virginia
United States	Homestead Associates Site Number : 8400004	Miami	Florida
United States	Wellness Clinical Research (WCR) Site Number : 8400009	Miami Lakes	Florida
United States	Advanced Research Institute, Inc. Site Number : 8400026	New Port Richey	Florida
United States	DiGiovanna Institute for Medical Education and Research Site Number : 8400006	North Massapequa	New York
United States	Gastroenterology Consultants PC Site Number : 8400022	Roswell	Georgia
United States	Medrasa Clinical Research Site Number : 8400039	Sherman	Texas
United States	GI Alliance - Southlake Site Number : 8400013	Southlake	Texas
United States	Washington Gastroenterology Site Number : 8400030	Tacoma	Washington
United States	AdtreMed Site Number : 8400035	Tampa	Florida
United States	GCP Clinical Research Site Number : 8400014	Tampa	Florida
United States	Clinical Trials Management Service Site Number : 8400034	Thousand Oaks	California
United States	Tyler Research Institute Site Number : 8400031	Tyler	Texas
United States	Gastro Health & Nutrition Site Number : 8400019	Victoria	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  Japan,  Korea, Republic of,  Mexico,  Puerto Rico,  South Africa,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants who are in clinical remission at 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.	Week 24
Secondary	Proportion of participants achieving clinical response by modified Mayo score at 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.	Week 24 and Week 52
Secondary	Proportion of participants who are in clinical remission by modified Mayo score at 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.	Week 52
Secondary	Proportion of participants in symptomatic remission over time	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.	Baseline up to Week 52
Secondary	Proportion of participants achieving histologic-endoscopic healing at 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.	Week 24 and Week 52
Secondary	Proportion of participants with a Mayo endoscopic subscore of 0 or 1 without friability at Week 24, and Week 52	The Mayo endoscopic subscore ranges 0-3 with higher scores indicating greater disease severity.	Week 24 and Week 52
Secondary	Proportion of participants with a Mayo endoscopic subscore of 0 at Week 24, and Week 52	The Mayo endoscopic subscore ranges 0-3 with higher scores indicating greater disease severity.	Week 24 and Week 52
Secondary	Change from baseline in the partial Mayo score at 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.	Baseline to Week 8, Week 24 and Week 52
Secondary	Proportion of participants in clinical remission at Week 52 who are off concomitant oral corticosteroids (OCS) at least 4 weeks prior 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.	Baseline up to Week 52
Secondary	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	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.	Baseline up to Week 52
Secondary	Change from baseline in abdominal pain assessed by Abdominal Pain Numerical Rating Scale (NRS) at 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'.	Baseline to Week 8, Week 24 and Week 52
Secondary	Incidence of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)		Baseline up to Week 64
Secondary	Concentration of dupilumab in serum over time.		Baseline up to Week 64
Secondary	Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab.		Baseline up to Week 64
Secondary	Change from baseline (Screening visit) in the normalized enrichment scores (NES) in type 2 inflammation transcriptome signature at Week 24 and Week 52.	NES is a summary score of the expression of a specified set of genes defining a molecular phenotype.	Baseline to Week 24 and Week 52