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

Millennium Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Ulcerative Colitis

Treatments: Other: Placebo; Drug: vedolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00783718

09/H1102/66 (Registry Identifier)

CTRI/2009/091/000128 (Registry Identifier)

C13006

NMRR-08-1046-2201 (Registry Identifier)

U1111-1156-8422 (Registry Identifier)

2008-002782-32 (EudraCT Number)

C13006CTIL (Other Identifier)

NL25207.096.08 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 895 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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895 participants in 2 patient groups, including a placebo group

Vedolizumab

Experimental group

Description:

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.

Treatment:

Drug: vedolizumab

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo