Study of Vedolizumab in Patients With Moderate to Severe Crohn's Disease (GEMINI III)

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction of Clinical Response and Remission by Vedolizumab in Patients With Moderate to Severe Crohn's Disease

This study in patients with moderately to severely active Crohn's disease is designed to establish the efficacy and safety of vedolizumab for the induction of clinical response and remission.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Other: Placebo; Drug: vedolizumab

Detailed Description

After completing the study, patients were eligible to enroll in a long term safety study with continued access to vedolizumab (study C13008; NCT00790933) if study drug was well tolerated, and no major surgical intervention for Crohn's disease occurred or was required.

Participants who did not enroll in Study C13008 were to complete the Final Safety visit (16 weeks after the last dose of study drug) for a maximum time on study of 22 weeks.

• Study Type: Interventional
• Enrollment (Actual): 416
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G2X8
      • Zeidler Ledcor Center-Univerisity of Alberta
• United States
  • Colorado
    • Lafayette, Colorado, United States, 80026
      • Gastroenterology of the Rockies
  • Connecticut
    • Hamden, Connecticut, United States, 65180
      • Gastroenterology Center of Connecticut P.C.
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Winter Park, Florida, United States, 32789
      • Shafran Gastroenterology Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Atlanta Gastroenterology Associates
    • Macon, Georgia, United States, 31201
      • Gastroenterology Associates of Central Georgia
    • Suwanee, Georgia, United States, 30024
      • Atlanta Gastroenterology Specialist PC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Digestive Health Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
    • Louisville, Kentucky, United States, 40402
      • University of Louisville
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Gastroenterology Associates
    • Hammond, Louisiana, United States, 70403
      • Gastroenterology Research Of New Orleans
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Metropolitan Gastroenterology Group P.C.
    • Hollywood, Maryland, United States, 20636
      • Mid-Atlantic Medical Research Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Crohn's and Colitis Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Troy, Michigan, United States, 48098
      • Center for Digestive Health
    • Ypsilanti, Michigan, United States, 48197
      • Huron Gastroenterology Associates
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Minnesota Gastroenterology P.A.
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Great Neck, New York, United States, 11021
      • Long Island Clinical Research Associates
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina At Chapel Hill
    • Charlotte, North Carolina, United States, 28207
      • Charlotte Gastroenterology and Hepatology P.L.L.C
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Consultants for Clinical Research Inc.
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Options Health Research
  • Oregon
    • Portland, Oregon, United States, 97225
      • The Oregon Clinic-West Hills Gastroenterology
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Consultants in Gastroenterology
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastroenterology Center of the MidSouth PC
  • Texas
    • San Antonio, Texas, United States, 78229
      • Gastroenterology Clinic of San Antonio
    • Tyler, Texas, United States, 75701
      • Digestive Health Specialists of Tyler
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington School of Medicine
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advanced Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 to 80
• Diagnosis of moderately to severely active Crohn's disease
• Crohn's Disease involvement of the ileum and/or colon
• Demonstrated, over the previous 5 year period, an inadequate response to, loss of response to, or intolerance of at least one conventional therapy as defined by the protocol
• 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
• History of >3 small bowel resections or diagnosis of short bowel syndrome
• Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
• Have received non permitted therapies within either 30 or 60 days, depending on the medication, as stated in the protocol
• Chronic hepatitis B or C infection; human immunodeficiency virus (HIV) infection
• Active or latent tuberculosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Other: Placebo; Placebo intravenous infusion
Experimental: Vedolizumab; Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.	Drug: vedolizumab; Vedolizumab for intravenous infusion; Other Names: Entyvio; MLN0002; MLN02; LDP-02

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in Clinical Remission in the Tumor Necrosis Factor Alpha (TNFα) Antagonist Failure Subpopulation	Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.	Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in Clinical Remission at Week 6 in the Overall Population	Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.	Week 6
Percentage of Participants in Clinical Remission at Week 10 in the TNFα Antagonist Failure Subpopulation	Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.	Week 10
Percentage of Participants in Clinical Remission at Week 10 in the Overall Population	Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.	Week 10
Percentage of Participants With Sustained Clinical Remission in the TNFα Antagonist Failure Population	Sustained clinical remission is defined as a CDAI score ≤ 150 points at both Week 6 and Week 10. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving sustained clinical remission.	Week 6 and Week 10
Percentage of Participants With Sustained Clinical Remission in the Overall Population	Sustained clinical remission is defined as a CDAI score ≤ 150 points at both Week 6 and Week 10. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving sustained clinical remission.	Week 6 and Week 10
Percentage of Participants With Enhanced Clinical Response at Week 6 in the TNFα Antagonist Failure Subpopulation	Enhanced clinical response is defined as a ≥ 100-point decrease in CDAI score from Baseline. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percent deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving enhanced clinical response.	Baseline and Week 6
Number of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a patient administered a pharmaceutical product, which did not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was any AE, occurring at any dose and regardless of causality that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was an important medical event based upon appropriate medical judgment that may have jeopardized the patient and may have required medical or surgical intervention to prevent 1 of the outcomes listed above, or any diagnosis of progressive multifocal leukoencephalopathy (PML). Relationship to study drug administration was determined by the investigator responding yes or no to the question: Is there a reasonable possibility that the AE is associated with the study drug?	From the date of first study drug administration to Week 22, through the 14 March 2012 database lock date. At the time of this database lock, 7 patients had completed Week 10 or early termination assessments but not Week 22 assessments.

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• 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.
• 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.
• 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. Erratum In: Clin Gastroenterol Hepatol. 2020 Mar;18(3):759.
• 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.
• 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. Erratum In: Aliment Pharmacol Ther. 2015 Nov;42(9):1135.
• Sands BE, Feagan BG, Rutgeerts P, Colombel JF, Sandborn WJ, Sy R, D'Haens G, Ben-Horin S, Xu J, Rosario M, Fox I, Parikh A, Milch C, Hanauer S. Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology. 2014 Sep;147(3):618-627.e3. doi: 10.1053/j.gastro.2014.05.008. Epub 2014 May 21.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: October 18, 2010
• First Submitted That Met QC Criteria: October 18, 2010
• First Posted (Estimate): October 19, 2010

Study Record Updates

• Last Update Posted (Estimate): July 21, 2014
• Last Update Submitted That Met QC Criteria: June 19, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Gastrointestinal Agents; Vedolizumab
• Other Study ID Numbers: C13011; U1111-1158-2581 (Registry Identifier: WHO); 2009-016488-12 (EudraCT Number); NL34356.078.10 (Registry Identifier: CCMO)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No