Clinical trial NCT05731128: 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))
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colitis Ulcerative
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2023-02-16
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of participants who are in clinical remission at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Proportion of participants achieving clinical response by modified Mayo score at Week 24 and Week 52
timeFrame: Week 24 and Week 52
measure: Proportion of participants who are in clinical remission by modified Mayo score at Week 52
timeFrame: Week 52
measure: Proportion of participants in symptomatic remission over time
timeFrame: Baseline up to Week 52
measure: Proportion of participants achieving histologic-endoscopic healing at Week 24, and Week 52
timeFrame: Week 24 and Week 52
measure: Proportion of participants with a Mayo endoscopic subscore of 0 or 1 without friability at Week 24, and Week 52
timeFrame: Week 24 and Week 52
measure: Proportion of participants with a Mayo endoscopic subscore of 0 at Week 24, and Week 52
timeFrame: Week 24 and Week 52
measure: Change from baseline in the partial Mayo score at Week 8, Week 24, and Week 52
timeFrame: Baseline to Week 8, Week 24 and Week 52
measure: Proportion of participants in clinical remission at Week 52 who are off concomitant oral corticosteroids (OCS) at least 4 weeks prior to Week 52
timeFrame: Baseline up to Week 52
measure: 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
timeFrame: Baseline up to Week 52
measure: Change from baseline in abdominal pain assessed by Abdominal Pain Numerical Rating Scale (NRS) at Week 8, Week 24, and Week 52
timeFrame: Baseline to Week 8, Week 24 and Week 52
measure: Incidence of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)
timeFrame: Baseline up to Week 64
measure: Concentration of dupilumab in serum over time.
timeFrame: Baseline up to Week 64
measure: Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab.
timeFrame: Baseline up to Week 64
measure: Change from baseline (Screening visit) in the normalized enrichment scores (NES) in type 2 inflammation transcriptome signature at Week 24 and Week 52.
timeFrame: Baseline to Week 24 and Week 52
Other outcomes:
Locations:
city: Apple Valley
country: United States
facility: Om Research- Site Number : 8400029
state: California
city: Beverly Hills
country: United States
facility: TLC Clinical Research- Site Number : 8400020
state: California
city: Camarillo
country: United States
facility: Ventura County Gastroenterology Medical Group- Site Number : 8400028
state: California
city: Palm Springs
country: United States
facility: Palmtree Clinical Research- Site Number : 8400048
state: California
city: Thousand Oaks
country: United States
facility: Clinical Trials Management Services - Thousand Oaks- Site Number : 8400034
state: California
city: Miami Lakes
country: United States
facility: Wellness Clinical Research - Miami Lakes- Site Number : 8400009
state: Florida
city: Miami
country: United States
facility: Homestead Associates in Research- Site Number : 8400004
state: Florida
city: Naples
country: United States
facility: GI PROS Research- Site Number : 8400046
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute - New Port Richey- Site Number : 8400026
state: Florida
city: Orange Park
country: United States
facility: Digestive Disease Consultants - Orange Park- Site Number : 8400042
state: Florida
city: Pembroke Pines
country: United States
facility: Tellabio International Research Services- Site Number : 8400041
state: Florida
city: Tampa
country: United States
facility: GCP Clinical Research- Site Number : 8400014
state: Florida
city: Roswell
country: United States
facility: Gastroenterology Consultants - Roswell- Site Number : 8400022
state: Georgia
city: East Orange
country: United States
facility: Sanmora Bespoke Clinical Research Solutions- Site Number : 8400043
state: New Jersey
city: Jackson Heights
country: United States
facility: Smart Medical Research Inc- Site Number : 8400037
state: New York
city: Massapequa
country: United States
facility: DiGiovanna Family Care- Site Number : 8400006
state: New York
city: Charlotte
country: United States
facility: Tryon Medical Partners - Charlotte - Piedmont Row Drive South- Site Number : 8400008
state: North Carolina
city: Lumberton
country: United States
facility: Care Access - Lumberton- Site Number : 8400018
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC Presbyterian- Site Number : 8400038
state: Pennsylvania
city: Decatur
country: United States
facility: Advanced Gastroenterology Associates, PA- Site Number : 8400047
state: Texas
city: Katy
country: United States
facility: Katy Integrative Gastroenterology- Site Number : 8400027
state: Texas
city: Sherman
country: United States
facility: Medrasa Clinical Research - Medrasa Sherman- Site Number : 8400039
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants - Southlake- Site Number : 8400013
state: Texas
city: Tyler
country: United States
facility: Digestive Health Specialists of Tyler- Site Number : 8400031
state: Texas
city: Victoria
country: United States
facility: Victoria Gastroenterology- Site Number : 8400019
state: Texas
city: Bellevue
country: United States
facility: Washington Gastroenterology - Bellevue- Site Number : 8400025
state: Washington
city: Tacoma
country: United States
facility: Washington Gastroenterology - Tacoma- Site Number : 8400030
state: Washington
city: Mar Del Plata
country: Argentina
facility: Investigational Site Number : 0320006
state: Buenos Aires
city: San Miguel de Tucumán
country: Argentina
facility: Investigational Site Number : 0320001
state: Tucumán
city: San Miguel de Tucumán
country: Argentina
facility: Investigational Site Number : 0320004
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320007
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320002
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320008
city: Edmonton
country: Canada
facility: Investigational Site Number : 1240007
state: Alberta
city: Scarborough
country: Canada
facility: Investigational Site Number : 1240010
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number : 1240006
state: Quebec
city: Montreal
country: Canada
facility: Investigational Site Number : 1240003
state: Quebec
city: Concepción
country: Chile
facility: Investigational Site Number : 1520001
state: Biobío
city: Santiago
country: Chile
facility: Investigational Site Number : 1520005
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520003
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520006
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520002
state: Reg Metropolitana De Santiago
city: Nagoya
country: Japan
facility: Investigational Site Number : 3920006
state: Aichi
city: Kashiwa
country: Japan
facility: Investigational Site Number : 3920005
state: Chiba
city: Kitakyushu
country: Japan
facility: Investigational Site Number : 3920008
state: Fukuoka
city: Sapporo
country: Japan
facility: Investigational Site Number : 3920002
state: Hokkaido
city: Sapporo
country: Japan
facility: Investigational Site Number : 3920001
state: Hokkaido
city: Kamakura
country: Japan
facility: Investigational Site Number : 3920011
state: Kanagawa
city: Shimizu
country: Japan
facility: Investigational Site Number : 3920010
state: Shizuoka
city: Bunkyo
country: Japan
facility: Investigational Site Number : 3920004
state: Tokyo
city: Kyoto
country: Japan
facility: Investigational Site Number : 3920007
city: Saitama
country: Japan
facility: Investigational Site Number : 3920009
city: Haeundae-gu
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Busan-gwangyeoksi
city: Daegu
country: Korea, Republic of
facility: Investigational Site Number : 4100005
state: Daegu-gwangyeoksi
city: Daejeon
country: Korea, Republic of
facility: Investigational Site Number : 4100006
state: Daejeon-gwangyeoksi
city: Wonju-si
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Gangwon-do
city: Daegu
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Gyeongsangbuk-do
city: Mexico City
country: Mexico
facility: Investigational Site Number : 4840004
state: Ciudad De Mexico
city: Saltillo
country: Mexico
facility: Investigational Site Number : 4840005
state: Coahuila De Zaragoza
city: Torreón
country: Mexico
facility: Investigational Site Number : 4840002
state: Coahuila De Zaragoza
city: Guadalajara
country: Mexico
facility: Investigational Site Number : 4840007
state: Jalisco
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840003
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico - Medical Sciences Campus- Site Number : 6300002
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100005
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100009
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100002
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100007
city: Gqeberha
country: South Africa
facility: Investigational Site Number : 7100003
city: Johannesburg
country: South Africa
facility: Investigational Site Number : 7100008
city: Johannesburg
country: South Africa
facility: Investigational Site Number : 7100006
city: Johannesburg
country: South Africa
facility: Investigational Site Number : 7100001
city: Pretoria
country: South Africa
facility: Investigational Site Number : 7100004
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580002
city: Akdeniz
country: Turkey
facility: Investigational Site Number : 7920001
city: Gaziantep
country: Turkey
facility: Investigational Site Number : 7920003
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920005
city: Zonguldak
country: Turkey
facility: Investigational Site Number : 7920006
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: