Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Ulcerative Colitis

Phase 3

Completed

Conditions: Ulcerative Colitis

Interventions: Other: Placebo
Drug: vedolizumab

Registration Number: NCT00783718

Lead Sponsor: Millennium Pharmaceuticals, Inc.

Brief Summary: The primary purpose of this study was to determine the effect of vedolizumab induction treatment on clinical response at 6 weeks and to determine the effect of vedolizumab maintenance treatment on clinical remission at 52 weeks.

Detailed Description: This multicenter, phase 3, randomized, blinded, placebo-controlled study in patients with moderately to severely active ulcerative colitis comprises two phases:

* The Induction Phase, designed to establish the efficacy and safety of vedolizumab for the induction of clinical response and remission.

* The Maintenance Phase, designed to establish the efficacy and safety of vedolizumab for the maintenance of clinical response and remission.

The 6-week Induction Phase contained 2 cohorts of participants: Cohort 1 participants were randomized and treated with double-blind study drug, and Cohort 2 participants were treated with open-label vedolizumab. The second cohort was enrolled to ensure that the sample size of Induction Phase responders randomized into the Maintenance Study provided sufficient power for the Maintenance Study primary efficacy analysis. These participants did not contribute to the efficacy analyses performed for the Induction Study. Participants in both cohorts were assessed for treatment response at Week 6.

In the Maintenance Phase vedolizumab-treated participants from both Cohort 1 and Cohort 2 who demonstrated a clinical response were randomized in a 1:1:1 ratio to double-blind treatment with vedolizumab administered every 4 weeks (Q4W), vedolizumab administered every 8 weeks (Q8W), or placebo. Vedolizumab-treated participants who did not demonstrate response at Week 6 continued treatment with open-label vedolizumab, administered Q4W. Participants treated with double-blind placebo in the Induction Phase continued on double-blind placebo during the Maintenance Phase, regardless of treatment response during induction. The Maintenance Phase began at Week 6 and concluded with Week 52 assessments.

After the Week 52 assessments, participants meeting protocol-defined criteria were eligible to enroll in Study C13008 (NCT00790933; Long-term Safety) to receive open-label vedolizumab treatment. Participants who withdrew early (prior to Week 52) due to sustained nonresponse, disease worsening, or the need for rescue medications may also have been eligible for Study C13008. Participants who did not enroll into Study C13008 were to complete a final on-study safety assessment at Week 66 (or final safety visit 16 weeks after the last dose) in the Maintenance Phase of Study C13006.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 895

Inclusion Criteria

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

Diagnosis of moderately to severely active ulcerative colitis
Demonstrated, over the previous 5 year period, an inadequate response to, loss of response to, or intolerance at least 1 of the following agents:
1. Immunomodulators
2. Tumor necrosis factor-alpha (TNFα) antagonists
3. Corticosteroids
May be receiving a therapeutic dose of conventional therapies for inflammatory bowel disease (IBD) as defined by the protocol

Exclusion Criteria

Evidence of abdominal abscess at the initial screening visit
Extensive colonic resection, subtotal or total colectomy
Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
Have received non permitted IBD therapies within either 30 or 60 days, depending on the medication, as stated in the protocol
Chronic hepatitis B or C infection
Active or latent tuberculosis

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	In the Induction Phase participants received placebo intravenous infusion at Week 0 and Week 2 (Days 1 and 15). Participants continued to receive placebo during the Maintenance Phase, regardless of treatment response during Induction.
Vedolizumab	vedolizumab	In the Induction Phase participants received vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 (Days 1 and 15). In the Maintenance Phase, participants who demonstrated a clinical response at Week 6 according to protocol-specified criteria were randomized in a 1:1:1 ratio to double-blind treatment with vedolizumab administered every 4 weeks, vedolizumab administered every 8 weeks, or placebo for up to Week 50. Participants who did not demonstrate response at Week 6 of the Induction Phase continued treatment with vedolizumab, administered every 4 weeks during the Maintenance Phase.

Primary Outcome Measures

Name	Time	Method
Induction Phase: Percentage of Participants With a Clinical Response at Week 6	Baseline and Week 6	Clinical response is defined as a reduction in complete Mayo score of ≥ 3 points and ≥ 30% from Baseline with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving clinical response.
Maintenance Phase: Percentage of Participants in Clinical Remission at Week 52	Week 52	Clinical Remission is defined as a complete Mayo score of ≤ 2 points and no individual subscore \> 1 point. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.

Secondary Outcome Measures

Name	Time	Method
Induction Phase: Percentage of Participants in Clinical Remission at Week 6	Week 6	Clinical Remission is defined as a complete Mayo score of ≤ 2 points and no individual subscore \> 1 point. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.
Induction Phase: Percentage of Participants With Mucosal Healing at Week 6	Week 6	Mucosal healing is defined as a Mayo endoscopic subscore of ≤ 1 point. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Endoscopic findings were scored on a scale from 0 to 3 as follows: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern, mild friability); 2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). All participants who prematurely discontinued for any reason were considered as not achieving mucosal healing.
Maintenance Phase: Percentage of Participants With Durable Clinical Response	Baseline, Week 6 and Week 52	Durable clinical response is defined as reduction in complete Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at both Weeks 6 and 52. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving durable clinical response.
Maintenance Phase: Percentage of Participants With Mucosal Healing at Week 52	Week 52	Mucosal healing is defined as a Mayo endoscopic subscore of ≤ 1 point. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Endoscopic findings were scored on a scale from 0 to 3 as follows: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern, mild friability); 2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). All participants who prematurely discontinued for any reason were considered as not achieving mucosal healing.
Maintenance Phase: Percentage of Participants With Durable Clinical Remission	Week 6 and Week 52	Durable clinical remission is defined as complete Mayo score of ≤ 2 points and no individual subscore \> 1 point at both Weeks 6 and 52. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving durable clinical remission.
Maintenance Phase: Percentage of Participants With Corticosteroid-free Remission at Week 52	Week 52	Clinical Remission is defined as a complete Mayo score of ≤ 2 points and no individual subscore \> 1 point. Corticosteroid-free clinical remission is defined as participants using oral corticosteroids at baseline (Week 0) who discontinued corticosteroids and were in clinical remission at Week 52. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving corticosteroid-free remission.

Trial Locations

Locations (104): Gastroenterology Associates of Central Georgia
🇺🇸
Macon, Georgia, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Boston Medical Center
🇺🇸
Boston, Massachusetts, United States
University of Miami Miller School of Medicine
🇺🇸
Miami, Florida, United States
Baylor College Of Medicine
🇺🇸
Houston, Texas, United States
Arapahoe Gastroenterology Associates P.C
🇺🇸
Littleton, Colorado, United States
Paramount Medical Specialty
🇺🇸
Montebello, California, United States
Gastrointestinal Bioscience
🇺🇸
Los Angeles, California, United States
Gastroenterology of the Rockies
🇺🇸
Lafayette, Colorado, United States
South Denver Gastroenterology
🇺🇸
Lone Tree, Colorado, United States
Lynn Institute of Pueblo
🇺🇸
Pueblo, Colorado, United States
Gastroenterology Center of Connecticut, P.C.
🇺🇸
Hamden, Connecticut, United States
University of Florida, Jacksonville
🇺🇸
Jacksonville, Florida, United States
University of Florida
🇺🇸
Gainesville, Florida, United States
East Coast Institute for Research
🇺🇸
Jacksonville, Florida, United States
Borland-Groover Clinic
🇺🇸
Jacksonville, Florida, United States
Osler Clinical Research
🇺🇸
Melbourne, Florida, United States
United Medical Research Institute
🇺🇸
New Smyrna Beach, Florida, United States
West Wind'r Research & Development, LLC
🇺🇸
Tampa, Florida, United States
Shafran Gastroenterology Center
🇺🇸
Winter Park, Florida, United States
Atlanta Gastroenterology Associates
🇺🇸
Atlanta, Georgia, United States
Southeast Regional Research Group
🇺🇸
Columbus, Georgia, United States
Atlanta Center for Gastroenterology, P.C.
🇺🇸
Decatur, Georgia, United States
Digestive Research Associates
🇺🇸
Newnan, Georgia, United States
St. Joseph's/Candler Health System
🇺🇸
Savannah, Georgia, United States
Digestive & Liver Consultants
🇺🇸
Clive, Iowa, United States
Carle Clinic Association P.C.
🇺🇸
Urbana, Illinois, United States
DLW Research System
🇺🇸
Snellville, Georgia, United States
Iowa Digestive Disease Center
🇺🇸
Clive, Iowa, United States
Cotton O'Neil Digestive Health Center
🇺🇸
Topeka, Kansas, United States
University Of Kansas
🇺🇸
Kansas City, Kansas, United States
University of Kentucky Medical Center
🇺🇸
Lexington, Kentucky, United States
Gastroenterology Associates
🇺🇸
Baton Rouge, Louisiana, United States
University of Maryland Medical Group
🇺🇸
Baltimore, Maryland, United States
Metropolitan Gastroenterology Group, P.C.
🇺🇸
Chevy Chase, Maryland, United States
Shah Associates
🇺🇸
Prince Frederick, Maryland, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
The Center for Clinical Studies
🇺🇸
Dearborn, Michigan, United States
Center for Digestive Health
🇺🇸
Troy, Michigan, United States
Minnesota Gastroenterology, P.A.
🇺🇸
Plymouth, Minnesota, United States
Gastroenterology Associates of Western Michigan, P.L.C.
🇺🇸
Wyoming, Michigan, United States
Center for Digestive and Liver Diseases, Inc.
🇺🇸
Mexico, Missouri, United States
Dartmouth-Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Washington University
🇺🇸
St. Louis, Missouri, United States
Affiliates in Gastroenterology PA
🇺🇸
Morristown, New Jersey, United States
The Gastroenterology Group of South Jersey
🇺🇸
Vineland, New Jersey, United States
University of Medicine and Dentistry of New Jersey-NJMS
🇺🇸
New Brunswick, New Jersey, United States
Hepatobiliary Associates of New York
🇺🇸
Bayside, New York, United States
Digestive Health Physician
🇺🇸
Cheektowaga, New York, United States
Long Island Clinical Research Associates
🇺🇸
Great Neck, New York, United States
Long Island Gastroenterology Group, P.C.
🇺🇸
Merrick, New York, United States
New York Presbyterian Hospital
🇺🇸
New York, New York, United States
Present Chapman Marion Steinlauf MD PC
🇺🇸
New York, New York, United States
Kim, Chung MD (Private Practice)
🇺🇸
Pittsford, New York, United States
SUNY Stony Brook University Medical Center
🇺🇸
Stonybrook, New York, United States
Long Island Digestive Disease Consultants
🇺🇸
Setauket, New York, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Syracuse Gastroenterological Associates
🇺🇸
Syracuse, New York, United States
Charlotte Gastroentology and Hepatology, P.L.L.C
🇺🇸
Charlotte, North Carolina, United States
Northwest Piedmont Clinical Research, Inc.
🇺🇸
Elkin, North Carolina, United States
Burke Research Associates
🇺🇸
Morganton, North Carolina, United States
Dayton Science Institute
🇺🇸
Dayton, Ohio, United States
Options Health Research
🇺🇸
Tulsa, Oklahoma, United States
Gastroenterology Center of the MidSouth, PC
🇺🇸
Germantown, Tennessee, United States
Austin Gastroenterology, PA
🇺🇸
Austin, Texas, United States
Bayou City Research, Ltd.
🇺🇸
Houston, Texas, United States
Jacon Medical Research Associates
🇺🇸
Houston, Texas, United States
Gastroenterology Consultants
🇺🇸
Houston, Texas, United States
Digestive Health Center
🇺🇸
Pasadena, Texas, United States
Gastroenterology Associates of Northern Virginia
🇺🇸
Fairfax, Virginia, United States
Digestive and Liver Disease Specialist Ltd
🇺🇸
Norfolk, Virginia, United States
Digestive Health Specialists of Tyler
🇺🇸
Tyler, Texas, United States
University of Virginia Health System
🇺🇸
Charlottesville, Virginia, United States
Granite Peaks Gastroenterology
🇺🇸
Sandy, Utah, United States
Puget Sound Medical Research
🇺🇸
Edmonds, Washington, United States
Hunter Holmes McGuire VA Medical Center
🇺🇸
Richmond, Virginia, United States
Pharmaseek, LLC
🇵🇷
Ponce, Puerto Rico
Zeidler Ledcor Center-Univerisity of Alberta
🇨🇦
Edmonton, Alberta, Canada
Royal University Hospital
🇨🇦
Saskatoon, Saskatchewan, Canada
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Apex Clinical Trials
🇺🇸
Birmingham, Alabama, United States
Clinical Applications Laboratories Inc.
🇺🇸
San Diego, California, United States
Desta Digestive Disease Medical Center
🇺🇸
San Diego, California, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Consultants for Clinical Research Inc.
🇺🇸
Cincinnati, Ohio, United States
The Oregon Clinic-West Hills Gastroenterology
🇺🇸
Portland, Oregon, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Alamo Medical Research
🇺🇸
San Antonio, Texas, United States
Gastroenterology Clinic of San Antonio
🇺🇸
San Antonio, Texas, United States
Stone Oak Research Foundation
🇺🇸
San Antonio, Texas, United States
Wisconsin Center for Advanced Research
🇺🇸
Milwaukee, Wisconsin, United States
Medical College Of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
St. Louis Center for Clinical Research
🇺🇸
St. Louis, Missouri, United States
Rocky Mountain Gastroenterology Associates P.L.L.C.
🇺🇸
Lakewood, Colorado, United States
Capital Gastroenterology Consultants Medical Group
🇺🇸
Sacramento, California, United States
University of Colorado Health Sciences Center
🇺🇸
Aurora, Colorado, United States
University of South Florida
🇺🇸
Tampa, Florida, United States
University of Pittsburgh Medical Center - Cancer Centers
🇺🇸
Pittsburgh, Pennsylvania, United States
Compass Research LLC
🇺🇸
Orlando, Florida, United States
Internal Medicine Specialists
🇺🇸
Orlando, Florida, United States
University Of Louisville
🇺🇸
Louisville, Kentucky, United States
Truman Medical Center
🇺🇸
Kansas City, Missouri, United States
University of North Carolina at Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Medical University Of SC CAR
🇺🇸
Charleston, South Carolina, United States