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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00783718
First received: October 31, 2008
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Ulcerative Colitis
Drug: vedolizumab
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients With Moderate to Severe Ulcerative Colitis

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Induction Phase: Percentage of Participants With a Clinical Response at Week 6 [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

    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:
  • Induction Phase: Percentage of Participants in Clinical Remission at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline, Week 6 and Week 52 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Week 6 and Week 52 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

    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.



Enrollment: 895
Study Start Date: January 2009
Study Completion Date: March 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: vedolizumab
Vedolizumab for intravenous infusion
Other Names:
  • Entyvio
  • MLN0002
  • MLN02
  • LDP-02
Placebo Comparator: 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.
Other: Placebo
Placebo intravenous infusion

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

  1. Diagnosis of moderately to severely active ulcerative colitis
  2. 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
  3. May be receiving a therapeutic dose of conventional therapies for inflammatory bowel disease (IBD) as defined by the protocol

Exclusion Criteria:

  1. Evidence of abdominal abscess at the initial screening visit
  2. Extensive colonic resection, subtotal or total colectomy
  3. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
  4. Have received non permitted IBD therapies within either 30 or 60 days, depending on the medication, as stated in the protocol
  5. Chronic hepatitis B or C infection
  6. Active or latent tuberculosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00783718

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
Apex Clinical Trials
Birmingham, Alabama, United States, 35234
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Gastrointestinal Bioscience
Los Angeles, California, United States, 90067
Paramount Medical Specialty
Montebello, California, United States, 90640
Capital Gastroenterology Consultants Medical Group
Sacramento, California, United States, 95815
Desta Digestive Disease Medical Center
San Diego, California, United States, 92114
Clinical Applications Laboratories Inc.
San Diego, California, United States, 92103
United States, Colorado
University of Colorado Health Sciences Center
Aurora, Colorado, United States, 80045
Gastroenterology of the Rockies
Lafayette, Colorado, United States, 80026
Rocky Mountain Gastroenterology Associates P.L.L.C.
Lakewood, Colorado, United States, 80215
Arapahoe Gastroenterology Associates P.C
Littleton, Colorado, United States, 80120
South Denver Gastroenterology
Lone Tree, Colorado, United States, 80124
Lynn Institute of Pueblo
Pueblo, Colorado, United States, 81007
United States, Connecticut
Gastroenterology Center of Connecticut, P.C.
Hamden, Connecticut, United States, 06518
United States, Florida
University of Florida
Gainesville, Florida, United States, 32608
Borland-Groover Clinic
Jacksonville, Florida, United States, 32256
University of Florida, Jacksonville
Jacksonville, Florida, United States, 32209
East Coast Institute for Research
Jacksonville, Florida, United States, 32223
Osler Clinical Research
Melbourne, Florida, United States, 32901
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
United Medical Research Institute
New Smyrna Beach, Florida, United States, 32168
Internal Medicine Specialists
Orlando, Florida, United States, 32806
Compass Research LLC
Orlando, Florida, United States, 32806
West Wind'r Research & Development, LLC
Tampa, Florida, United States, 33607
University of South Florida
Tampa, Florida, United States, 33606
Shafran Gastroenterology Center
Winter Park, Florida, United States, 32789
United States, Georgia
Atlanta Gastroenterology Associates
Atlanta, Georgia, United States, 30342
Southeast Regional Research Group
Columbus, Georgia, United States, 31904
Atlanta Center for Gastroenterology, P.C.
Decatur, Georgia, United States, 30033
Gastroenterology Associates of Central Georgia
Macon, Georgia, United States, 31201
Digestive Research Associates
Newnan, Georgia, United States, 30263
St. Joseph's/Candler Health System
Savannah, Georgia, United States, 31405
DLW Research System
Snellville, Georgia, United States, 30039
United States, Illinois
Carle Clinic Association P.C.
Urbana, Illinois, United States, 61801
United States, Iowa
Iowa Digestive Disease Center
Clive, Iowa, United States, 50325
Digestive & Liver Consultants
Clive, Iowa, United States, 50325
United States, Kansas
University Of Kansas
Kansas City, Kansas, United States, 66160
Cotton O'Neil Digestive Health Center
Topeka, Kansas, United States, 66606
United States, Kentucky
University of Kentucky Medical Center
Lexington, Kentucky, United States, 40536
University Of Louisville
Louisville, Kentucky, United States, 40202
United States, Louisiana
Gastroenterology Associates
Baton Rouge, Louisiana, United States, 70809
United States, Maryland
University of Maryland Medical Group
Baltimore, Maryland, United States, 21201
Metropolitan Gastroenterology Group, P.C.
Chevy Chase, Maryland, United States, 20815
Shah Associates
Prince Frederick, Maryland, United States, 20678
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
The Center for Clinical Studies
Dearborn, Michigan, United States, 48124
Center for Digestive Health
Troy, Michigan, United States, 48098
Gastroenterology Associates of Western Michigan, P.L.C.
Wyoming, Michigan, United States, 49519
United States, Minnesota
Minnesota Gastroenterology, P.A.
Plymouth, Minnesota, United States, 55486
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Truman Medical Center
Kansas City, Missouri, United States, 64108
Center for Digestive and Liver Diseases, Inc.
Mexico, Missouri, United States, 65265
St. Louis Center for Clinical Research
St. Louis, Missouri, United States, 63128
Washington University
St. Louis, Missouri, United States, 63110
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Affiliates in Gastroenterology PA
Morristown, New Jersey, United States, 07960
University of Medicine and Dentistry of New Jersey-NJMS
New Brunswick, New Jersey, United States, 08903
The Gastroenterology Group of South Jersey
Vineland, New Jersey, United States, 08360
United States, New York
Hepatobiliary Associates of New York
Bayside, New York, United States, 11358
Digestive Health Physician
Cheektowaga, New York, United States, 14225
Long Island Clinical Research Associates
Great Neck, New York, United States, 11021
Long Island Gastroenterology Group, P.C.
Merrick, New York, United States, 11566
New York Presbyterian Hospital
New York, New York, United States, 10021
Present Chapman Marion Steinlauf MD PC
New York, New York, United States, 10028
Kim, Chung MD (Private Practice)
Pittsford, New York, United States, 14534
University of Rochester
Rochester, New York, United States, 14642
Long Island Digestive Disease Consultants
Setauket, New York, United States, 11733
SUNY Stony Brook University Medical Center
Stonybrook, New York, United States, 11794
Syracuse Gastroenterological Associates
Syracuse, New York, United States, 13210
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Charlotte Gastroentology and Hepatology, P.L.L.C
Charlotte, North Carolina, United States, 28207
Northwest Piedmont Clinical Research, Inc.
Elkin, North Carolina, United States, 28621
Burke Research Associates
Morganton, North Carolina, United States, 28655
United States, Ohio
Consultants for Clinical Research Inc.
Cincinnati, Ohio, United States, 45219
Dayton Science Institute
Dayton, Ohio, United States, 45415
United States, Oklahoma
Options Health Research
Tulsa, Oklahoma, United States, 74104
United States, Oregon
The Oregon Clinic-West Hills Gastroenterology
Portland, Oregon, United States, 97225
United States, Pennsylvania
University of Pittsburgh Medical Center - Cancer Centers
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Medical University Of SC CAR
Charleston, South Carolina, United States, 29425
United States, Tennessee
Gastroenterology Center of the MidSouth, PC
Germantown, Tennessee, United States, 38138
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Austin Gastroenterology, PA
Austin, Texas, United States, 78705
Baylor College Of Medicine
Houston, Texas, United States, 77030
Bayou City Research, Ltd.
Houston, Texas, United States, 77024
Gastroenterology Consultants
Houston, Texas, United States, 77034
Jacon Medical Research Associates
Houston, Texas, United States, 77090
Digestive Health Center
Pasadena, Texas, United States, 77504
Alamo Medical Research
San Antonio, Texas, United States, 78215
Stone Oak Research Foundation
San Antonio, Texas, United States, 78258
Gastroenterology Clinic of San Antonio
San Antonio, Texas, United States, 78229
Digestive Health Specialists of Tyler
Tyler, Texas, United States, 75701
United States, Utah
Granite Peaks Gastroenterology
Sandy, Utah, United States, 84094
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
Gastroenterology Associates of Northern Virginia
Fairfax, Virginia, United States, 22031
Digestive and Liver Disease Specialist Ltd
Norfolk, Virginia, United States, 23502
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, United States, 23249
United States, Washington
Puget Sound Medical Research
Edmonds, Washington, United States, 98026
United States, Wisconsin
Pharmaseek, LLC
Madison, Wisconsin, United States, 53717
Wisconsin Center for Advanced Research
Milwaukee, Wisconsin, United States, 53215
Medical College Of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
Zeidler Ledcor Center-Univerisity of Alberta
Edmonton, Alberta, Canada, T6G2X8
Canada, Saskatchewan
Royal University Hospital
Saskatoon, Saskatchewan, Canada, S7N 0W8
Puerto Rico
Pharmaseek, LLC
Ponce, Puerto Rico, 716
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Publications:
Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00783718     History of Changes
Other Study ID Numbers: C13006, U1111-1156-8422, 2008-002782-32, NL25207.096.08, CTRI/2009/091/000128, NMRR-08-1046-2201, C13006CTIL, 09/H1102/66
Study First Received: October 31, 2008
Results First Received: June 19, 2014
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases

ClinicalTrials.gov processed this record on October 19, 2014