Study of Vedolizumab in Patients With Moderate to Severe Crohn's Disease (GEMINI III)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01224171
First received: October 18, 2010
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

This study in patients with moderately to severely active Crohn's disease is designed to establish the efficacy and safety of vedolizumab for the induction of clinical response and remission.


Condition Intervention Phase
Crohn's Disease
Drug: vedolizumab
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/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 of Clinical Response and Remission by Vedolizumab in Patients With Moderate to Severe Crohn's Disease

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Percentage of Participants in Clinical Remission in the Tumor Necrosis Factor Alpha (TNFα) Antagonist Failure Subpopulation [ Time Frame: Week 6 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Percentage of Participants in Clinical Remission at Week 6 in the Overall Population [ Time Frame: Week 6 ] [ Designated as safety issue: No ]

    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.


  • Percentage of Participants in Clinical Remission at Week 10 in the TNFα Antagonist Failure Subpopulation [ Time Frame: Week 10 ] [ Designated as safety issue: No ]

    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.


  • Percentage of Participants in Clinical Remission at Week 10 in the Overall Population [ Time Frame: Week 10 ] [ Designated as safety issue: No ]

    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.


  • Percentage of Participants With Sustained Clinical Remission in the TNFα Antagonist Failure Population [ Time Frame: Week 6 and Week 10 ] [ Designated as safety issue: No ]

    Sustained clinical remission is defined as a CDAI score ≤ 150 points at both Week 6 and Week 10. 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 sustained clinical remission.


  • Percentage of Participants With Sustained Clinical Remission in the Overall Population [ Time Frame: Week 6 and Week 10 ] [ Designated as safety issue: No ]

    Sustained clinical remission is defined as a CDAI score ≤ 150 points at both Week 6 and Week 10. 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 sustained clinical remission.


  • Percentage of Participants With Enhanced Clinical Response at Week 6 in the TNFα Antagonist Failure Subpopulation [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]

    Enhanced clinical response is defined as a ≥ 100-point decrease in CDAI score from 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;
    • Percent 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 enhanced clinical response.


  • Number of Participants With Adverse Events (AEs) [ Time Frame: From the date of first study drug administration to Week 22, through the 14 March 2012 database lock date. At the time of this database lock, 7 patients had completed Week 10 or early termination assessments but not Week 22 assessments. ] [ Designated as safety issue: Yes ]

    An AE was defined as any untoward medical occurrence in a patient administered a pharmaceutical product, which did not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was any AE, occurring at any dose and regardless of causality that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was an important medical event based upon appropriate medical judgment that may have jeopardized the patient and may have required medical or surgical intervention to prevent 1 of the outcomes listed above, or any diagnosis of progressive multifocal leukoencephalopathy (PML).

    Relationship to study drug administration was determined by the investigator responding yes or no to the question: Is there a reasonable possibility that the AE is associated with the study drug?



Enrollment: 416
Study Start Date: November 2010
Study Completion Date: April 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Participants received placebo intravenous infusion at Weeks 0, 2 and 6.
Other: Placebo
Placebo intravenous infusion
Experimental: Vedolizumab
Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Drug: vedolizumab
Vedolizumab for intravenous infusion
Other Names:
  • Entyvio
  • MLN0002
  • MLN02
  • LDP-02

Detailed Description:

After completing the study, patients were eligible to enroll in a long term safety study with continued access to vedolizumab (study C13008; NCT00790933) if study drug was well tolerated, and no major surgical intervention for Crohn's disease occurred or was required.

Participants who did not enroll in Study C13008 were to complete the Final Safety visit (16 weeks after the last dose of study drug) for a maximum time on study of 22 weeks.

  Eligibility

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

Inclusion Criteria:

  • Age 18 to 80
  • Diagnosis of moderately to severely active Crohn's disease
  • Crohn's Disease 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 one conventional therapy as defined by the protocol
  • 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
  • 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 therapies within either 30 or 60 days, depending on the medication, as stated in the protocol
  • Chronic hepatitis B or C infection; human immunodeficiency virus (HIV) infection
  • 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: NCT01224171

  Hide Study Locations
Locations
United States, Colorado
Gastroenterology of the Rockies
Lafayette, Colorado, United States, 80026
United States, Connecticut
Gastroenterology Center of Connecticut P.C.
Hamden, Connecticut, United States, 65180
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
Shafran Gastroenterology Center
Winter Park, Florida, United States, 32789
United States, Georgia
Atlanta Gastroenterology Associates
Atlanta, Georgia, United States, 30342
Gastroenterology Associates of Central Georgia
Macon, Georgia, United States, 31201
Atlanta Gastroenterology Specialist PC
Suwanee, Georgia, United States, 30024
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Kansas
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, 40402
United States, Louisiana
Gastroenterology Associates
Baton Rouge, Louisiana, United States, 70809
Gastroenterology Research of New Orleans
Hammond, Louisiana, United States, 70403
United States, Maryland
Metropolitan Gastroenterology Group P.C.
Chevy Chase, Maryland, United States, 20815
Mid-Atlantic Medical Research Center
Hollywood, Maryland, United States, 20636
United States, Massachusetts
Massachusetts General Hospital Crohn's and Colitis Center
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Center for Digestive Health
Troy, Michigan, United States, 48098
Huron Gastroenterology Associates
Ypsilanti, Michigan, United States, 48197
United States, Minnesota
Minnesota Gastroenterology P.A.
Plymouth, Minnesota, United States, 55446
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
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 York
Long Island Clinical Research Associates
Great Neck, New York, United States, 11021
New York Presbyterian Hospital
New York, New York, United States, 10021
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Charlotte Gastroenterology and Hepatology P.L.L.C
Charlotte, North Carolina, United States, 28207
United States, Ohio
Consultants for Clinical Research Inc.
Cincinnati, Ohio, United States, 45219
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, South Carolina
Consultants in Gastroenterology
Columbia, South Carolina, United States, 29203
United States, Tennessee
Gastroenterology Center of the MidSouth PC
Germantown, Tennessee, United States, 38138
United States, Texas
Gastroenterology Clinic of San Antonio
San Antonio, Texas, United States, 78229
Digestive Health Specialists of Tyler
Tyler, Texas, United States, 75701
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
United States, Washington
University of Washington School of Medicine
Seattle, Washington, United States, 98195
United States, Wisconsin
Medical College Of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Wisconsin Center for Advanced Research
Milwaukee, Wisconsin, United States, 53215
Canada, Alberta
Zeidler Ledcor Center-Univerisity of Alberta
Edmonton, Alberta, Canada, T6G2X8
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided by Millennium Pharmaceuticals, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01224171     History of Changes
Other Study ID Numbers: C13011, U1111-1158-2581, 2009-016488-12, NL34356.078.10
Study First Received: October 18, 2010
Results First Received: June 19, 2014
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Crohn Disease
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on October 21, 2014