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

Ulcerative Colitis Clinical Trial

— GEMINI I  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00783718
• Other study ID #: C13006
• Secondary ID: U1111-1156-84222
• Status: Completed
• Phase: Phase 3
• First received: October 31, 2008
• Last updated: June 19, 2014
• Start date: January 2009
• Est. completion date: March 2012

Study information

• Verified date: June 2014
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 895
• Est. completion date: March 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 (TNFa) 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• vedolizumab
Vedolizumab for intravenous infusion

Other:
• Placebo
Placebo intravenous infusion

Locations

Country	Name	City	State
Canada	Zeidler Ledcor Center-Univerisity of Alberta	Edmonton	Alberta
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Puerto Rico	Pharmaseek, LLC	Ponce
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	University of Colorado Health Sciences Center	Aurora	Colorado
United States	Austin Gastroenterology, PA	Austin	Texas
United States	University of Maryland Medical Group	Baltimore	Maryland
United States	Gastroenterology Associates	Baton Rouge	Louisiana
United States	Hepatobiliary Associates of New York	Bayside	New York
United States	Apex Clinical Trials	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University Of SC CAR	Charleston	South Carolina
United States	Charlotte Gastroentology and Hepatology, P.L.L.C	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Digestive Health Physician	Cheektowaga	New York
United States	Metropolitan Gastroenterology Group, P.C.	Chevy Chase	Maryland
United States	Consultants for Clinical Research Inc.	Cincinnati	Ohio
United States	Digestive & Liver Consultants	Clive	Iowa
United States	Iowa Digestive Disease Center	Clive	Iowa
United States	Southeast Regional Research Group	Columbus	Georgia
United States	Dayton Science Institute	Dayton	Ohio
United States	The Center for Clinical Studies	Dearborn	Michigan
United States	Atlanta Center for Gastroenterology, P.C.	Decatur	Georgia
United States	Puget Sound Medical Research	Edmonds	Washington
United States	Northwest Piedmont Clinical Research, Inc.	Elkin	North Carolina
United States	Gastroenterology Associates of Northern Virginia	Fairfax	Virginia
United States	University of Florida	Gainesville	Florida
United States	Gastroenterology Center of the MidSouth, PC	Germantown	Tennessee
United States	Long Island Clinical Research Associates	Great Neck	New York
United States	Gastroenterology Center of Connecticut, P.C.	Hamden	Connecticut
United States	Baylor College Of Medicine	Houston	Texas
United States	Bayou City Research, Ltd.	Houston	Texas
United States	Gastroenterology Consultants	Houston	Texas
United States	Jacon Medical Research Associates	Houston	Texas
United States	Borland-Groover Clinic	Jacksonville	Florida
United States	East Coast Institute for Research	Jacksonville	Florida
United States	University of Florida, Jacksonville	Jacksonville	Florida
United States	Truman Medical Center	Kansas City	Missouri
United States	University Of Kansas	Kansas City	Kansas
United States	Gastroenterology of the Rockies	Lafayette	Colorado
United States	Rocky Mountain Gastroenterology Associates P.L.L.C.	Lakewood	Colorado
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Arapahoe Gastroenterology Associates P.C	Littleton	Colorado
United States	South Denver Gastroenterology	Lone Tree	Colorado
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Gastrointestinal Bioscience	Los Angeles	California
United States	University Of Louisville	Louisville	Kentucky
United States	Gastroenterology Associates of Central Georgia	Macon	Georgia
United States	Pharmaseek, LLC	Madison	Wisconsin
United States	Osler Clinical Research	Melbourne	Florida
United States	Long Island Gastroenterology Group, P.C.	Merrick	New York
United States	Center for Digestive and Liver Diseases, Inc.	Mexico	Missouri
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Medical College Of Wisconsin	Milwaukee	Wisconsin
United States	Wisconsin Center for Advanced Research	Milwaukee	Wisconsin
United States	Paramount Medical Specialty	Montebello	California
United States	Burke Research Associates	Morganton	North Carolina
United States	Affiliates in Gastroenterology PA	Morristown	New Jersey
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Medicine and Dentistry of New Jersey-NJMS	New Brunswick	New Jersey
United States	United Medical Research Institute	New Smyrna Beach	Florida
United States	New York Presbyterian Hospital	New York	New York
United States	Present Chapman Marion Steinlauf MD PC	New York	New York
United States	Digestive Research Associates	Newnan	Georgia
United States	Digestive and Liver Disease Specialist Ltd	Norfolk	Virginia
United States	Compass Research LLC	Orlando	Florida
United States	Internal Medicine Specialists	Orlando	Florida
United States	Digestive Health Center	Pasadena	Texas
United States	University of Pittsburgh Medical Center - Cancer Centers	Pittsburgh	Pennsylvania
United States	Kim, Chung MD (Private Practice)	Pittsford	New York
United States	Minnesota Gastroenterology, P.A.	Plymouth	Minnesota
United States	The Oregon Clinic-West Hills Gastroenterology	Portland	Oregon
United States	Shah Associates	Prince Frederick	Maryland
United States	Lynn Institute of Pueblo	Pueblo	Colorado
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Capital Gastroenterology Consultants Medical Group	Sacramento	California
United States	Alamo Medical Research	San Antonio	Texas
United States	Gastroenterology Clinic of San Antonio	San Antonio	Texas
United States	Stone Oak Research Foundation	San Antonio	Texas
United States	Clinical Applications Laboratories Inc.	San Diego	California
United States	Desta Digestive Disease Medical Center	San Diego	California
United States	Granite Peaks Gastroenterology	Sandy	Utah
United States	St. Joseph's/Candler Health System	Savannah	Georgia
United States	Long Island Digestive Disease Consultants	Setauket	New York
United States	DLW Research System	Snellville	Georgia
United States	St. Louis Center for Clinical Research	St. Louis	Missouri
United States	Washington University	St. Louis	Missouri
United States	SUNY Stony Brook University Medical Center	Stonybrook	New York
United States	Syracuse Gastroenterological Associates	Syracuse	New York
United States	University of South Florida	Tampa	Florida
United States	West Wind'r Research & Development, LLC	Tampa	Florida
United States	Cotton O'Neil Digestive Health Center	Topeka	Kansas
United States	Center for Digestive Health	Troy	Michigan
United States	Options Health Research	Tulsa	Oklahoma
United States	Digestive Health Specialists of Tyler	Tyler	Texas
United States	Carle Clinic Association P.C.	Urbana	Illinois
United States	The Gastroenterology Group of South Jersey	Vineland	New Jersey
United States	Shafran Gastroenterology Center	Winter Park	Florida
United States	Gastroenterology Associates of Western Michigan, P.L.C.	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

References & Publications (1)

Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative coliti — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Induction Phase: Percentage of Participants With a Clinical Response at 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.	Baseline and Week 6	No
Primary	Maintenance Phase: Percentage of Participants in Clinical Remission at 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.	Week 52	No
Secondary	Induction Phase: Percentage of Participants in Clinical Remission at 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.	Week 6	No
Secondary	Induction Phase: Percentage of Participants With Mucosal Healing at 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.	Week 6	No
Secondary	Maintenance Phase: Percentage of Participants With Durable Clinical Response	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.	Baseline, Week 6 and Week 52	No
Secondary	Maintenance Phase: Percentage of Participants With Mucosal Healing at 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.	Week 52	No
Secondary	Maintenance Phase: Percentage of Participants With Durable Clinical Remission	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.	Week 6 and Week 52	No
Secondary	Maintenance Phase: Percentage of Participants With Corticosteroid-free Remission at 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.	Week 52	No