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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00783718
Recruitment Status : Completed
First Posted : November 2, 2008
Results First Posted : July 18, 2014
Last Update Posted : July 18, 2014
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE October 31, 2008
First Posted Date  ICMJE November 2, 2008
Results First Submitted Date  ICMJE June 19, 2014
Results First Posted Date  ICMJE July 18, 2014
Last Update Posted Date July 18, 2014
Study Start Date  ICMJE January 2009
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2014)
  • Induction Phase: Percentage of Participants With a Clinical Response at Week 6 [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 31, 2008)
  • Proportion of patients with clinical response [ Time Frame: Week 6 ]
  • Proportion of patients in clinical remission [ Time Frame: Week 52 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2014)
  • Induction Phase: Percentage of Participants in Clinical Remission at Week 6 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2008)
  • Proportion of patients in clinical remission [ Time Frame: Week 6 ]
  • Proportion of patients in clinical response [ Time Frame: Week 52 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Ulcerative Colitis
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis
Intervention  ICMJE
  • Drug: vedolizumab
    Vedolizumab for intravenous infusion
    Other Names:
    • Entyvio
    • MLN0002
    • MLN02
    • LDP-02
  • Other: Placebo
    Placebo intravenous infusion
Study Arms  ICMJE
  • 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.

    Intervention: Drug: vedolizumab
  • 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.
    Intervention: Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 6, 2012)		 895
Original Estimated Enrollment  ICMJE
 (submitted: October 31, 2008)		 826
Actual Study Completion Date  ICMJE March 2012
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00783718
Other Study ID Numbers  ICMJE C13006
U1111-1156-8422 ( Registry Identifier: WHO )
2008-002782-32 ( EudraCT Number )
NL25207.096.08 ( Registry Identifier: CCMO )
CTRI/2009/091/000128 ( Registry Identifier: CTRI )
NMRR-08-1046-2201 ( Registry Identifier: NMRR )
C13006CTIL ( Other Identifier: Israel MoH )
09/H1102/66 ( Registry Identifier: NRES )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Millennium Pharmaceuticals, Inc.
Original Responsible Party Asit Parikh, M.D., Associate Medical Director, Millennium Pharmaceuticals, Inc.
Current Study Sponsor  ICMJE Millennium Pharmaceuticals, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
PRS Account Millennium Pharmaceuticals, Inc.
Verification Date June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP