Etrasimod Versus Placebo for the Treatment of Moderately Active Ulcerative Colitis
- Registration Number
- NCT04607837
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to determine whether oral etrasimod is a safe and effective treatment for moderately active ulcerative colitis in adult participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 234
- Diagnosed with Ulcerative Colitis (UC) ≥ 3 months prior to screening
- Active UC confirmed by endoscopy
- Moderately active UC defined as a modified Mayo score of 4 to 6 and an endoscopic score ≥ 2 and rectal bleeding score ≥ 1
- Received a surveillance colonoscopy within 12 months before baseline
- Severe extensive colitis
- Diagnosis of Crohn's disease or indeterminate colitis or the presence or history of a fistula consistent with Crohn's disease
- Diagnosis of microscopic colitis, ischemic colitis, or infectious colitis
- Hospitalization for exacerbation of UC requiring intravenous steroids within 12 weeks prior to or after screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - Etrasimod 2 mg Etrasimod -
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Clinical Remission (CR) at Week 52 Using Modified Mayo Score (MMS) Week 52 MMS is used to assess disease activity in participants with UC and has following components: endoscopic score(ES),rectal bleeding(RB),stool frequency(SF).Each component score ranges from 0 to 3(0=normal,1=mild,2=moderate,3=severe); higher scores indicating more severe disease.ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy,scores ranged from 0(normal or inactive disease) to 3(severe disease \[spontaneous bleeding, ulceration\]).RB reported most severe amount of blood passed per rectum in 24-hour period,scores ranged from 0(no blood seen) to 3(blood alone passes).SF reported number of stools in 24-hour period relative to normal number of stools for that participant in same period,scores ranged from 0(normal number of stools) to 3(5 or more stools than normal).CR per FDA draft guidance defined as:SF=0 or 1 and no greater than baseline, RB=0,ES less than or equal to (\<=)1(excluding friability).Percentage of participants achieving CR at Week 52 was evaluated.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving Clinical Remission at Week 12 Using MMS Week 12 MMS is used to assess disease activity in participants with UC and has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe); higher scores indicating more severe disease. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, scores ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]). RB reported the most severe amount of blood passed per rectum in a 24-hour period, scores ranged from 0 (no blood seen) to 3 (blood alone passes). SF reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0 (normal number of stools) to 3 (5 or more stools than normal). CR per FDA draft guidance was defined as: SF=0 or =1 and no greater than baseline, RB=0, and ES \<=1 (excluding friability). Percentage of participants achieving CR at Week 12 was evaluated in this endpoint.
Percentage of Participants Achieving Endoscopic Improvement at Week 52 Week 52 Endoscopic improvement was defined as ES \<=1 (excluding friability). ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. Percentage of participants achieving endoscopic improvement at Week 52 was evaluated in this endpoint.
Percentage of Participants Achieving Symptomatic Remission at Week 52 Week 52 Symptomatic remission was defined as SF =0 (or = 1 with a \>= 1 point decrease from baseline) and RB =0. SF subscore: reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, scores ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. Percentage of participants achieving symptomatic remission at Week 52 was evaluated in this endpoint.
Percentage of Participants Achieving Complete Symptomatic Remission at Week 52 Week 52 Complete symptomatic remission was defined as participants with RB = 0 and SF = 0. SF subscore: reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, scores ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. Percentage of participants achieving complete symptomatic remission at Week 52 was evaluated in this endpoint.
Percentage of Participants Achieving Histologic-Endoscopic Mucosal Improvement at Week 52 Week 52 Histologic-endoscopic mucosal improvement was defined as ES \<=1 (excluding friability) with Geboes score \<2.0. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. The Geboes score grading system was a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicated more severe disease. Percentage of participants achieving mucosal improvement at Week 52 was evaluated in this endpoint.
Percentage of Participants Achieving Clinical Remission at Both Weeks 12 and 52 [Combined] Using MMS Weeks 12 and 52 [Combined] MMS is used to assess disease activity in participants with UC and has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0= normal, 1= mild, 2= moderate, 3= severe); higher scores = more severe disease. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease). RB: reported the most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0 (no blood seen) to 3 (blood alone passes). SF reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0 (normal number of stools) to 3 (5 or more stools than normal). Clinical remission per FDA draft guidance: SF =0 or =1 and no greater than baseline, RB =0, and ES \<=1 (excluding friability). Percentage of participants who achieved clinical remission at both the time points Week 12 and Week 52 \[Combined\] are reported.
Percentage of Participants With 12-Week Corticosteroid-Free Clinical Remission at Week 52 Among Participants Receiving Corticosteroids at Baseline Using MMS Week 52 MMS has following components:ES, RB and SF. Each component score ranges from 0 to 3(0=normal,1=mild,2=moderate,3=severe); higher scores indicating more severe disease. ES:worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease)to 3(severe disease). RB:most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen)to 3(blood alone passes). SF:number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0(normal number of stools)to 3(5 or more stools than normal). CR per FDA draft guidance as: SF =0 or =1 and no greater than baseline, RB=0, and ES \<=1(excluding friability). 12-week corticosteroid-free CR was defined as CR at Week 52 and corticosteroid-free for \>=12 weeks immediately prior to Week 52. The baseline was balanced between treatment groups and representative of participants with mildly to moderately active UC.
Percentage of Participants With 12-Week Corticosteroid-Free Clinical Remission at Week 52 Using MMS Week 52 MMS has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0=normal,1=mild,2=moderate,3=severe); higher scores indicating more severe disease. ES: worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease) to 3 (severe disease). RB: most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen) to 3 (blood alone passes). SF: number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0(normal number of stools) to 3 (5 or more stools than normal). CR per FDA draft guidance as: SF =0 or =1 and no greater than baseline, RB=0, and ES \<=1(excluding friability). 12-week corticosteroid-free CR was defined as CR at Week 52 and corticosteroid-free for \>=12 weeks immediately prior to Week 52.
Percentage of Participants Achieving 4-Week Corticosteroid-Free Clinical Remission at Week 52 Among Participants Receiving Corticosteroids at Baseline Using MMS Week 52 MMS has following components: ES, RB and SF; each ranged as 0=normal,1=mild,2=moderate,3=severe; total MMS score 0-9; higher scores=more severe disease. ES:worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease)to 3(severe disease). RB:most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen) to 3(blood alone passes). SF:number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0(normal number of stools)to 3(5 or more stools than normal). CR per FDA draft guidance as: SF =0 or =1 and no greater than baseline, RB=0, and ES \<=1(excluding friability). 4-week corticosteroid-free CR was defined as CR at Week 52 and corticosteroid-free for \>=4 weeks immediately prior to Week 52. The baseline was balanced between treatment groups and representative of participants with mildly to moderately active UC.
Percentage of Participants With 4-Week Corticosteroid-Free Clinical Remission at Week 52 Using MMS Week 52 MMS has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0=normal,1=mild,2=moderate,3=severe); where total score is sum of three components giving total MMS score as 0 to 9; higher scores indicating more severe disease. ES: worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease) to 3 (severe disease). RB: most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen) to 3 (blood alone passes). SF: number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0 (normal number of stools) to 3 (5 or more stools than normal). CR per FDA draft guidance as: SF =0 or =1 and no greater than baseline, RB=0, and ES \<=1(excluding friability). 4-week corticosteroid-free CR was defined as CR at Week 52 and corticosteroid-free for \>=4 weeks immediately prior to Week 52.
Percentage of Participants Achieving Clinical Response at Week 12 Using MMS Week 12 Clinical response was defined as a \>=2-point and \>=30 percentage (%) decrease from baseline in MMS, and a \>=1-point decrease from baseline in RB subscore or an absolute RB subscore \<=1 and is as per FDA draft guidance. MMS was used to assess disease activity in participants with UC and has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0= normal, 1= mild, 2= moderate, 3= severe); where total score is sum of three components giving total MMS score as 0 to 9; higher scores indicating more severe disease. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]). Percentage of participants achieving clinical response at Week 12 was evaluated in this endpoint.
Percentage of Participants Achieving Clinical Response at Week 52 Using MMS Week 52 Clinical response was defined as a \>=2-point and \>=30 % decrease from baseline in MMS, and a \>=1-point decrease from baseline in RB subscore or an absolute RB subscore \<=1 and is as per FDA draft guidance. MMS is used to assess disease activity in participants with UC and has following components: ES, RB and SF. Each component scores ranges from 0 to 3 (0= normal, 1= mild, 2= moderate, 3= severe); where total score is sum of three components giving total MMS score as 0 to 9; higher scores indicating more severe disease. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, scores ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]). Percentage of participants achieving clinical response at Week 52 was evaluated in this endpoint.
Percentage of Participants Achieving Endoscopic Improvement at Week 12 Week 12 Endoscopic improvement was defined as ES \<=1 (excluding friability). ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, scores ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. Percentage of participants achieving endoscopic improvement at Week 12 was evaluated in this endpoint.
Percentage of Participants Achieving Histologic-Endoscopic Mucosal Improvement at Week 12 Week 12 Histologic-endoscopic mucosal improvement was defined as ES \<=1 (excluding friability) with Geboes score \<2.0. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, scores ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. The Geboes score grading system was a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicated more severe disease. Percentage of participants achieving mucosal improvement at Week 12 was evaluated in this endpoint.
Percentage of Participants Achieving Symptomatic Remission at Week 12 Week 12 Symptomatic remission was defined as SF =0 (or = 1 with a \>= 1 point decrease from baseline) and RB =0. SF subscore: reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, scores ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, scores ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. Percentage of participants achieving symptomatic remission at Week 12 was evaluated in this endpoint.
Percentage of Participants Achieving Complete Symptomatic Remission at Week 12 Week 12 Complete symptomatic remission was defined as participants with RB = 0 and SF = 0. SF subscore: reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, scores ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, scores ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. Percentage of participants achieving complete symptomatic remission at Week 12 was evaluated in this endpoint.
Percentage of Participants Achieving Change From Baseline in Both ES and RB or in Both ES and SF at Week 12 Baseline to Week 12 ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, scores ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. RB: reported the most severe amount of blood passed per rectum in a 24-hour period, scores ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. SF reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. Percentage of participants with reduction from baseline in both ES and RB or in both ES and SF at Week 12 was evaluated in this endpoint. The baseline primary analysis set was balanced between treatment groups and representative of participants with mildly to moderately active UC.
Percentage of Participants Achieving Histologic Response Based on the Geboes Grading System at Week 12 Week 12 Histologic response based on the Geboes grading system was defined as Geboes score \<=3.1. The Geboes score grading system is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicated more severe disease. Percentage of participants achieving histologic response based on the Geboes grading system at week 12 was evaluated in this endpoint.
Percentage of Participants Achieving Histologic Response Based on Robarts Histopathology Index (RHI) at Week 12 Week 12 RHI is an evaluative index, derived from the Geboes score, that is designed to be reproducible and responsive to clinically meaningful change in disease activity over time. Histologic response based on RHI was defined as decrease in RHI of \>=7 points from baseline. Total RHI score ranges from 0 (no disease activity) to 33 (severe disease activity), higher score = more severity. Percentage of participants achieving histologic response based on RHI at Week 12 was evaluated in this endpoint.
Trial Locations
- Locations (283)
Center for Digestive Health (Colonoscopy Location)
🇺🇸Dothan, Alabama, United States
Digestive Health Specialists
🇺🇸Dothan, Alabama, United States
Dothan Eyecare-Dr. Brent McKinley (OCT Location)
🇺🇸Dothan, Alabama, United States
Pulmonary Associates (Secondary PFT Location)
🇺🇸Dothan, Alabama, United States
Flowers Hospital (PFT Location)
🇺🇸Dothan, Alabama, United States
Arizona Retina Institute/ Phoenix Retina Associates(OCT)
🇺🇸Peoria, Arizona, United States
SimonMed Imaging (Imaging)
🇺🇸Peoria, Arizona, United States
Sun City Endoscopy (Endoscopy)
🇺🇸Sun City, Arizona, United States
Euclid Endoscopy Center-El Cajon (Endoscopy procedure only)
🇺🇸El Cajon, California, United States
Center for Clinical Research (CCR)
🇺🇸Irvine, California, United States
Scroll for more (273 remaining)Center for Digestive Health (Colonoscopy Location)🇺🇸Dothan, Alabama, United States