Clinical trial NCT00783692: Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Crohn's Disease
Official title: A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab (MLN0002) in Patients With Moderate to Severe Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn's Disease
Lead sponsor: Millennium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2008-11-02
Enrollment: 1116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study was to determine the effect of vedolizumab induction treatment on clinical response and remission at 6 weeks and to determine the effect of vedolizumab maintenance treatment on clinical remission at 52 weeks.

Detailed description: Study C13007 comprised 2 randomized, double-blind, placebo-controlled studies conducted under 1 protocol which, operationally, consisted of 2 phases.

* The Induction Phase, designed to establish the efficacy and safety of vedolizumab for the induction of clinical response and clinical remission, and
* The Maintenance Phase, designed to establish the efficacy and safety of vedolizumab for the maintenance of clinical response and clinical 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 may have been eligible to enroll in Study C13008 (NCT00790933; Long-term Safety Study) 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 have been eligible to enroll in 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 C13007.

Eligibility criteria: Inclusion Criteria:

1. Age 18 to 80
2. Diagnosis of moderately to severely active Crohn's disease (CD)
3. CD involvement of the ileum and/or colon
4. Demonstrated, over the previous 5 year period, an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents, within protocol-specified parameters:

   1. Immunomodulators
   2. Tumor necrosis factor-alpha (TNFα) antagonists
   3. Corticosteroids
5. May be receiving a therapeutic dose of conventional therapies for irritable bowel disease (IBD) defined by the protocol

Exclusion Criteria

1. Evidence of abdominal abscess at the initial screening visit, other than a minimum of 10 aphthous ulcerations involving a minimum of 10 contiguous cm of intestine
2. Extensive colonic resection, subtotal or total colectomy
3. History of \>3 small bowel resections or diagnosis of short bowel syndrome
4. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
5. Have received non permitted IBD therapies within either 30 or 60 days, depending on the medication, as stated in the protocol
6. Chronic hepatitis B or C infection
7. Active or latent tuberculosis

Primary outcomes:
measure: Induction Phase: Percentage of Participants Achieving Clinical Remission at Week 6
timeFrame: Week 6
measure: Induction Phase: Percentage of Participants With Enhanced Clinical Response at Week 6
timeFrame: Baseline and Week 6
measure: Maintenance Phase: Percentage of Participants Achieving Clinical Remission at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: Induction Phase: Change From Baseline in C-Reactive Protein (CRP) Levels at Week 6
timeFrame: Baseline and Week 6
measure: Maintenance Phase: Percentage of Participants With Enhanced Clinical Response at Week 52
timeFrame: Baseline and Week 52
measure: Maintenance Phase: Percentage of Participants in Corticosteroid-free Clinical Remission at Week 52
timeFrame: Week 52
measure: Maintenance Phase: Percentage of Participants With Durable Clinical Remission
timeFrame: Assessed every 4 weeks from Week 6 to Week 50, and at Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: Apex Clinical Trials
state: Alabama
city: Los Angeles
country: United States
facility: Gastrointestinal Bioscience
state: California
city: Montebello
country: United States
facility: Paramount Medical Specialty
state: California
city: Sacramento
country: United States
facility: Capital Gastroenterology Consultants Medical Group
state: California
city: San Diego
country: United States
facility: Clinical Applications Laboratories Inc.
state: California
city: San Diego
country: United States
facility: Desta Digestive Disease Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Golden
country: United States
facility: Rocky Mountain Clinical Research, LLC
state: Colorado
city: Lafayette
country: United States
facility: Gastroenterology of the Rockies
state: Colorado
city: Littleton
country: United States
facility: Arapahoe Gastroenterology Associates P.C.
state: Colorado
city: Lone Tree
country: United States
facility: South Denver Gastroenterology
state: Colorado
city: Pueblo
country: United States
facility: Lynn Institute of Pueblo
state: Colorado
city: Bristol
country: United States
facility: Connecticut Gastroenterology Institute
state: Connecticut
city: Hamden
country: United States
facility: Gastroenterology Center of Connecticut, P.C.
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: University of Florida, Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: East Coast Institute for Research
state: Florida
city: Jacksonville
country: United States
facility: Borland-Groover Clinic
state: Florida
city: Maitland
country: United States
facility: Center for Advanced Gastroenterology
state: Florida
city: Melbourne
country: United States
facility: Osler Clinical Research
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: New Smyrna Beach
country: United States
facility: United Medical Research Institute
state: Florida
city: Orlando
country: United States
facility: Compass Research LLC
state: Florida
city: Orlando
country: United States
facility: Internal Medicine Specialists
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Tampa
country: United States
facility: West Wind'r Research & Development, LLC
state: Florida
city: Winter Park
country: United States
facility: Shafran Gastroenterology Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Columbus
country: United States
facility: Southeast Regional Research Group
state: Georgia
city: Decatur
country: United States
facility: Atlanta Center for Gastroenterology, P.C.
state: Georgia
city: Macon
country: United States
facility: Gastroenterology Associates of Central Georgia
state: Georgia
city: Newnan
country: United States
facility: Digestive Research Associates
state: Georgia
city: Savannah
country: United States
facility: St. Joseph's/Candler Health System
state: Georgia
city: Snellville
country: United States
facility: DLW Research System
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Clinic Association P.C.
state: Illinois
city: Indianapolis
country: United States
facility: Indianapolis Gastroenterology & Hepatology, Inc.- ARC
state: Indiana
city: Clive
country: United States
facility: Digestive & Liver Consultants
state: Iowa
city: Clive
country: United States
facility: Iowa Digestive Disease Center
state: Iowa
city: Kansas City
country: United States
facility: University Of Kansas
state: Kansas
city: Topeka
country: United States
facility: Cotton O'Neil Digestive Health Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Louisville
country: United States
facility: University Of Louisville
state: Kentucky
city: Baton Rouge
country: United States
facility: Gastroenterology Associates
state: Louisiana
city: Chevy Chase
country: United States
facility: Metropolitan Gastroenterology Group, P.C.
state: Maryland
city: Prince Frederick
country: United States
facility: Shah Associates
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Dearborn
country: United States
facility: The Center for Clinical Studies
state: Michigan
city: Troy
country: United States
facility: Center for Digestive Health
state: Michigan
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan, P.L.C.
state: Michigan
city: Plymouth
country: United States
facility: Minnesota Gastroenterology, P.A.
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Tupelo
country: United States
facility: Digestive Health Specialists
state: Mississippi
city: Kansas City
country: United States
facility: Truman Medical Center
state: Missouri
city: Mexico
country: United States
facility: Center for Digestive and Liver Diseases, Inc.
state: Missouri
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: St. Louis
country: United States
facility: St. Louis Center for Clinical Research
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Morristown
country: United States
facility: Affiliates in Gastroenterology PA
state: New Jersey
city: New Brunswick
country: United States
facility: University of Medicine and Dentistry of New Jersey-NJMS
state: New Jersey
city: Vineland
country: United States
facility: The Gastroenterology Group of South Jersey
state: New Jersey
city: Bayside
country: United States
facility: Hepatobiliary Associates of New York
state: New York
city: Cheektowaga
country: United States
facility: Digestive Health Physician
state: New York
city: Great Neck
country: United States
facility: Long Island Clinical Research Associates
state: New York
city: Merrick
country: United States
facility: Long Island Gastroenterology Group, P.C.
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Present Chapman Marion Steinlauf MD PC
state: New York
city: Pittsford
country: United States
facility: Kim, Chung MD (Private Practice)
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Setauket
country: United States
facility: Long Island Digestive Disease Consultants
state: New York
city: Stonybrook
country: United States
facility: SUNY Stony Brook University Medical Center
state: New York
city: Syracuse
country: United States
facility: Syracuse Gastroenterological Associates
state: New York
city: Asheville
country: United States
facility: Asheville Gastroenterology Associates, P.A.
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Gastroentology and Hepatology, P.L.L.C
state: North Carolina
city: Elkin
country: United States
facility: Northwest Piedmont Clinical Research, Inc.
state: North Carolina
city: Morganton
country: United States
facility: Burke Research Associates
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants for Clinical Research Inc.
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Dayton
country: United States
facility: Dayton Science Institute
state: Ohio
city: Tulsa
country: United States
facility: Options Health Research
state: Oklahoma
city: Portland
country: United States
facility: The Oregon Clinic-West Hills Gastroenterology
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Cancer Centers
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University Of SC CAR
state: South Carolina
city: Columbia
country: United States
facility: Consultants in Gastroenterology
state: South Carolina
city: Germantown
country: United States
facility: Gastroenterology Center of the MidSouth, PC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Austin Gastroenterology, PA
state: Texas
city: Houston
country: United States
facility: Bayou City Research, Ltd.
state: Texas
city: Houston
country: United States
facility: Gastroenterology Consultants
state: Texas
city: Houston
country: United States
facility: Jacon Medical Research Associates
state: Texas
city: Pasadena
country: United States
facility: Digestive Health Center
state: Texas
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Clinic of San Antonio
state: Texas
city: San Antonio
country: United States
facility: Stone Oak Research Foundation
state: Texas
city: Tyler
country: United States
facility: Digestive Health Specialists of Tyler
state: Texas
city: Sandy
country: United States
facility: Granite Peaks Gastroenterology
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Fairfax
country: United States
facility: Gastroenterology Associates of Northern Virginia
state: Virginia
city: Norfolk
country: United States
facility: Digestive and Liver Disease Specialist Ltd.
state: Virginia
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center
state: Virginia
city: Bellevue
country: United States
facility: Northwest Gastroenterology Associates
state: Washington
city: Edmonds
country: United States
facility: Puget Sound Medical Research
state: Washington
city: Madison
country: United States
facility: Pharmaseek, LLC
state: Wisconsin
city: Milwaukee
country: United States
facility: Wisconsin Center for Advanced Research
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College Of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: GI Research
state: Alberta
city: Edmonton
country: Canada
facility: Zeidler Ledcor Center-Univerisity of Alberta
state: Alberta
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Ponce
country: Puerto Rico
facility: Pharmaseek, LLC
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
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citation: Sands BE, Van Assche G, Tudor D, Akhundova-Unadkat G, Curtis RI, Tan T. Vedolizumab in Combination With Corticosteroids for Induction Therapy in Crohn's Disease: A Post Hoc Analysis of GEMINI 2 and 3. Inflamm Bowel Dis. 2019 Jul 17;25(8):1375-1382. doi: 10.1093/ibd/izy384.
citation: Feagan BG, Sandborn WJ, Colombel JF, Byrne SO, Khalid JM, Kempf C, Geransar P, Bhayat F, Rubin DT. Incidence of Arthritis/Arthralgia in Inflammatory Bowel Disease with Long-term Vedolizumab Treatment: Post Hoc Analyses of the GEMINI Trials. J Crohns Colitis. 2019 Jan 1;13(1):50-57. doi: 10.1093/ecco-jcc/jjy125.
citation: Feagan BG, Lasch K, Lissoos T, Cao C, Wojtowicz AM, Khalid JM, Colombel JF. Rapid Response to Vedolizumab Therapy in Biologic-Naive Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2019 Jan;17(1):130-138.e7. doi: 10.1016/j.cgh.2018.05.026. Epub 2018 May 29.
citation: Feagan BG, Schwartz D, Danese S, Rubin DT, Lissoos TW, Xu J, Lasch K. Efficacy of Vedolizumab in Fistulising Crohn's Disease: Exploratory Analyses of Data from GEMINI 2. J Crohns Colitis. 2018 Apr 27;12(5):621-626. doi: 10.1093/ecco-jcc/jjy019.
citation: Colombel JF, Sands BE, Rutgeerts P, Sandborn W, Danese S, D'Haens G, Panaccione R, Loftus EV Jr, Sankoh S, Fox I, Parikh A, Milch C, Abhyankar B, Feagan BG. The safety of vedolizumab for ulcerative colitis and Crohn's disease. Gut. 2017 May;66(5):839-851. doi: 10.1136/gutjnl-2015-311079. Epub 2016 Feb 18.
citation: Rosario M, Dirks NL, Gastonguay MR, Fasanmade AA, Wyant T, Parikh A, Sandborn WJ, Feagan BG, Reinisch W, Fox I. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease. Aliment Pharmacol Ther. 2015 Jul;42(2):188-202. doi: 10.1111/apt.13243. Epub 2015 May 20.
citation: Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A; GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013 Aug 22;369(8):711-21. doi: 10.1056/NEJMoa1215739.