Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Crohn's Disease
- Registration Number
- NCT00783692
- 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 and remission at 6 weeks and to determine the effect of vedolizumab maintenance treatment on clinical remission at 52 weeks.
- Detailed Description
Study C13007 comprised 2 randomized, double-blind, placebo-controlled studies conducted under 1 protocol which, operationally, consisted of 2 phases.
* The Induction Phase, designed to establish the efficacy and safety of vedolizumab for the induction of clinical response and clinical remission, and
* The Maintenance Phase, designed to establish the efficacy and safety of vedolizumab for the maintenance of clinical response and clinical 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 may have been eligible to enroll in Study C13008 (NCT00790933; Long-term Safety Study) 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 have been eligible to enroll in 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 C13007.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1116
-
Age 18 to 80
-
Diagnosis of moderately to severely active Crohn's disease (CD)
-
CD involvement of the ileum and/or colon
-
Demonstrated, over the previous 5 year period, an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents, within protocol-specified parameters:
- Immunomodulators
- Tumor necrosis factor-alpha (TNFα) antagonists
- Corticosteroids
-
May be receiving a therapeutic dose of conventional therapies for irritable bowel disease (IBD) defined by the protocol
Exclusion Criteria
- Evidence of abdominal abscess at the initial screening visit, other than a minimum of 10 aphthous ulcerations involving a minimum of 10 contiguous cm of intestine
- Extensive colonic resection, subtotal or total colectomy
- History of >3 small bowel resections or diagnosis of short bowel syndrome
- 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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- 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 Achieving Clinical Remission at Week 6 Week 6 Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points.
The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are:
* Number of liquid or soft stools each day for 7 days;
* Abdominal pain (graded from 0-3 on severity) each day for 7 days;
* General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;
* Presence of complications;
* Taking Lomotil or opiates for diarrhea;
* Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);
* Hematocrit of \< 0.47 in men and \< 0.42 in women;
* Percentage deviation from standard weight.
The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity.
All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.Induction Phase: Percentage of Participants With Enhanced Clinical Response at Week 6 Baseline and Week 6 Enhanced clinical response is defined as a CDAI score at least 100 points lower than Baseline. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are:
* Number of liquid or soft stools each day for 7 days;
* Abdominal pain (graded from 0-3 on severity) each day for 7 days;
* General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;
* Presence of complications;
* Taking Lomotil or opiates for diarrhea;
* Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);
* Hematocrit of \< 0.47 in men and \< 0.42 in women;
* Percentage deviation from standard weight.
The total score ranges from 0 to 600 with higher scores indicating greater disease activity.
All participants who prematurely discontinued for any reason were considered as not achieving enhanced clinical response.Maintenance Phase: Percentage of Participants Achieving Clinical Remission at Week 52 Week 52 Clinical remission is defined as a CDAI score ≤ 150. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are:
* Number of liquid or soft stools each day for 7 days;
* Abdominal pain (graded from 0-3 on severity) each day for 7 days;
* General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;
* Presence of complications;
* Taking Lomotil or opiates for diarrhea;
* Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);
* Hematocrit of \< 0.47 in men and \< 0.42 in women;
* Percentage deviation from standard weight.
The total score ranges from 0 to 600 with higher scores indicating 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: Change From Baseline in C-Reactive Protein (CRP) Levels at Week 6 Baseline and Week 6 C-reactive protein (CRP) is a protein found in the blood, the levels of which rise in response to inflammation. Normal concentration in healthy human serum is usually lower than 10 mg/L, slightly increasing with age. Higher levels indicate mild inflammation (10-40 mg/L) and active inflammation (40-200 mg/L).
Maintenance Phase: Percentage of Participants With Enhanced Clinical Response at Week 52 Baseline and Week 52 Enhanced clinical response is defined as a CDAI score at least 100 points lower than the Baseline value. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are:
* Number of liquid or soft stools each day for 7 days;
* Abdominal pain (graded from 0-3 on severity) each day for 7 days;
* General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;
* Presence of complications;
* Taking Lomotil or opiates for diarrhea;
* Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);
* Hematocrit of \< 0.47 in men and \< 0.42 in women;
* Percentage deviation from standard weight.
The total score ranges from 0 to 600 with higher scores indicating greater disease activity.
All participants who prematurely discontinued for any reason were considered as not achieving enhanced clinical response.Maintenance Phase: Percentage of Participants in Corticosteroid-free Clinical Remission at Week 52 Week 52 Participants using oral corticosteroids at Baseline, who discontinued corticosteroids and were in clinical remission (CDAI score ≤ 150) at Week 52 achieved corticosteroid-free clinical remission. The CDAI quantifies the symptoms of patients with Crohn's disease and consists of eight factors, summed after adjustment with a weighting factor. The total score ranges from 0 to 600 with higher scores indicating greater disease activity.
All participants who prematurely discontinued for any reason were considered as not achieving corticosteroid-free clinical remission.Maintenance Phase: Percentage of Participants With Durable Clinical Remission Assessed every 4 weeks from Week 6 to Week 50, and at Week 52 Durable clinical remission is defined as CDAI score ≤ 150 points at 80% or more of study visits during the Maintenance Phase, including the Week 52 visit (11 of 13 study visits). The CDAI quantifies the symptoms of patients with Crohn's disease and consists of eight factors, summed after adjustment with a weighting factor. The total score ranges from 0 to 600 with higher scores indicating greater disease activity.
All participants who prematurely discontinued for any reason were considered as not achieving durable clinical remission
Trial Locations
- Locations (113)
Puget Sound Medical Research
🇺🇸Edmonds, Washington, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Pittsburgh Medical Center - Cancer Centers
🇺🇸Pittsburgh, Pennsylvania, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Gastroenterology Consultants
🇺🇸Houston, Texas, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Paramount Medical Specialty
🇺🇸Montebello, California, United States
University of Florida, Jacksonville
🇺🇸Jacksonville, Florida, United States
Gastroenterology Associates of Central Georgia
🇺🇸Macon, Georgia, United States
DLW Research System
🇺🇸Snellville, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Carle Clinic Association P.C.
🇺🇸Urbana, Illinois, United States
Indianapolis Gastroenterology & Hepatology, Inc.- ARC
🇺🇸Indianapolis, Indiana, United States
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Metropolitan Gastroenterology Group, P.C.
🇺🇸Chevy Chase, Maryland, United States
Shah Associates
🇺🇸Prince Frederick, Maryland, United States
The Center for Clinical Studies
🇺🇸Dearborn, Michigan, United States
Center for Digestive Health
🇺🇸Troy, Michigan, United States
Gastroenterology Associates of Western Michigan, P.L.C.
🇺🇸Wyoming, Michigan, United States
Minnesota Gastroenterology, P.A.
🇺🇸Plymouth, Minnesota, United States
St. Louis Center for Clinical Research
🇺🇸St. Louis, Missouri, United States
Center for Digestive and Liver Diseases, Inc.
🇺🇸Mexico, Missouri, 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
Hepatobiliary Associates of New York
🇺🇸Bayside, New York, United States
Long Island Clinical Research Associates
🇺🇸Great Neck, New York, United States
Digestive Health Physician
🇺🇸Cheektowaga, New York, United States
Long Island Gastroenterology Group, P.C.
🇺🇸Merrick, New York, United States
Kim, Chung MD (Private Practice)
🇺🇸Pittsford, New York, United States
Present Chapman Marion Steinlauf MD PC
🇺🇸New York, New York, United States
Long Island Digestive Disease Consultants
🇺🇸Setauket, New York, United States
SUNY Stony Brook University Medical Center
🇺🇸Stonybrook, New York, United States
Syracuse Gastroenterological Associates
🇺🇸Syracuse, New York, United States
Asheville Gastroenterology Associates, P.A.
🇺🇸Asheville, North Carolina, United States
Burke Research Associates
🇺🇸Morganton, North Carolina, 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
Wake Forest University Baptist Medical Center
🇺🇸Winston Salem, North Carolina, United States
Options Health Research
🇺🇸Tulsa, Oklahoma, United States
Jacon Medical Research Associates
🇺🇸Houston, Texas, United States
Digestive Health Center
🇺🇸Pasadena, Texas, United States
Bayou City Research, Ltd.
🇺🇸Houston, Texas, United States
Austin Gastroenterology, PA
🇺🇸Austin, Texas, United States
Digestive Health Specialists of Tyler
🇺🇸Tyler, Texas, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Digestive and Liver Disease Specialist Ltd.
🇺🇸Norfolk, Virginia, United States
Gastroenterology Associates of Northern Virginia
🇺🇸Fairfax, Virginia, United States
Northwest Gastroenterology Associates
🇺🇸Bellevue, Washington, United States
Hunter Holmes McGuire VA Medical Center
🇺🇸Richmond, Virginia, United States
GI Research
🇨🇦Edmonton, Alberta, Canada
University Of Kansas
🇺🇸Kansas City, Kansas, United States
Cotton O'Neil Digestive Health Center
🇺🇸Topeka, Kansas, United States
New York Presbyterian Hospital
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Gastroenterology Associates
🇺🇸Baton Rouge, Louisiana, United States
University of Medicine and Dentistry of New Jersey-NJMS
🇺🇸New Brunswick, New Jersey, United States
Digestive Health Specialists
🇺🇸Tupelo, Mississippi, United States
Royal University Hospital
🇨🇦Saskatoon, Saskatchewan, Canada
Pharmaseek, LLC
🇵🇷Ponce, Puerto Rico
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Gastroenterology Center of the MidSouth, PC
🇺🇸Germantown, Tennessee, United States
Zeidler Ledcor Center-Univerisity of Alberta
🇨🇦Edmonton, Alberta, Canada
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
The Oregon Clinic-West Hills Gastroenterology
🇺🇸Portland, Oregon, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, 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
University of Colorado Health Sciences Center
🇺🇸Aurora, Colorado, United States
University of South Florida
🇺🇸Tampa, Florida, United States
West Wind'r Research & Development, LLC
🇺🇸Tampa, Florida, United States
Connecticut Gastroenterology Institute
🇺🇸Bristol, Connecticut, United States
Gastroenterology Center of Connecticut, P.C.
🇺🇸Hamden, Connecticut, United States
University of Florida
🇺🇸Gainesville, Florida, United States
East Coast Institute for Research
🇺🇸Jacksonville, Florida, United States
Atlanta Gastroenterology Associates
🇺🇸Atlanta, Georgia, United States
Borland-Groover Clinic
🇺🇸Jacksonville, Florida, United States
United Medical Research Institute
🇺🇸New Smyrna Beach, Florida, United States
Digestive Research Associates
🇺🇸Newnan, Georgia, United States
St. Joseph's/Candler Health System
🇺🇸Savannah, Georgia, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Atlanta Center for Gastroenterology, P.C.
🇺🇸Decatur, Georgia, United States
Center for Advanced Gastroenterology
🇺🇸Maitland, Florida, United States
Lynn Institute of Pueblo
🇺🇸Pueblo, Colorado, United States
Consultants for Clinical Research Inc.
🇺🇸Cincinnati, Ohio, United States
Gastrointestinal Bioscience
🇺🇸Los Angeles, California, United States
Rocky Mountain Clinical Research, LLC
🇺🇸Golden, Colorado, United States
Gastroenterology of the Rockies
🇺🇸Lafayette, Colorado, United States
Osler Clinical Research
🇺🇸Melbourne, Florida, United States
Southeast Regional Research Group
🇺🇸Columbus, Georgia, United States
Shafran Gastroenterology Center
🇺🇸Winter Park, Florida, United States
Granite Peaks Gastroenterology
🇺🇸Sandy, Utah, United States
Alamo Medical Research
🇺🇸San Antonio, Texas, United States
Consultants in Gastroenterology
🇺🇸Columbia, South Carolina, United States
Digestive & Liver Consultants
🇺🇸Clive, Iowa, United States
Iowa Digestive Disease Center
🇺🇸Clive, Iowa, United States
Dayton Science Institute
🇺🇸Dayton, Ohio, United States
Arapahoe Gastroenterology Associates P.C.
🇺🇸Littleton, Colorado, United States
South Denver Gastroenterology
🇺🇸Lone Tree, Colorado, United States
Medical College Of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Capital Gastroenterology Consultants Medical Group
🇺🇸Sacramento, California, 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
Medical University Of SC CAR
🇺🇸Charleston, South Carolina, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States