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

Phase 3

Completed

Conditions: Ulcerative Colitis

Interventions: Other: Placebo
Drug: vedolizumab

Registration Number: NCT00783718

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 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 895

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:
1. Immunomodulators
2. Tumor necrosis factor-alpha (TNFα) antagonists
3. 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

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 With a Clinical Response at Week 6	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	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 Outcome Measures

Name	Time	Method
Induction Phase: Percentage of Participants in Clinical Remission at Week 6	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	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	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	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	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	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.

Trial Locations

Locations (104): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Apex Clinical Trials
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Birmingham, Alabama, United States
Cedars-Sinai Medical Center
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Los Angeles, California, United States
Gastrointestinal Bioscience
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Los Angeles, California, United States
Paramount Medical Specialty
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Montebello, California, United States
Capital Gastroenterology Consultants Medical Group
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Sacramento, California, United States
Clinical Applications Laboratories Inc.
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San Diego, California, United States
Desta Digestive Disease Medical Center
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San Diego, California, United States
University of Colorado Health Sciences Center
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Aurora, Colorado, United States
Gastroenterology of the Rockies
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Lafayette, Colorado, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States