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Completed

NCT Number: NCT00783718

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

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.

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Key information

Conditions

Ulcerative Colitis Colitis Colitis, Ulcerative Colonic Diseases Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Inflammatory Bowel Diseases Intestinal Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Zeidler Ledcor Center-Univerisity of Alberta, Edmonton, Alberta, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • Immunomodulators
  • Tumor necrosis factor-alpha (TNFα) antagonists
  • 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

Treatment and study plan

Vedolizumab

Drug

Vedolizumab for intravenous infusion

Other names: Entyvio, MLN0002, MLN02, LDP-02

Placebo

Other

Placebo intravenous infusion

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

Sponsors and collaborators

Lead sponsor

Millennium Pharmaceuticals, Inc.

Industry

Registry information

Official study 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

Acronym: GEMINI I

Important dates

Study start
2009
Primary completion
2011
Study completion
2012
First posted
Nov 3, 2008
Registry last updated
Jul 18, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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