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

• ClinicalTrials.gov Identifier: NCT01224171
• Recruitment Status: Completed
• First Posted: October 19, 2010
• Results First Posted: July 21, 2014
• Last Update Posted: July 21, 2014
• Sponsor: Millennium Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Millennium Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: October 18, 2010
• First Posted Date: October 19, 2010
• Results First Submitted Date: June 19, 2014
• Results First Posted Date: July 21, 2014
• Last Update Posted Date: July 21, 2014
• Study Start Date: November 2010
• Actual Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 19, 2014)

Percentage of Participants in Clinical Remission in the Tumor Necrosis Factor Alpha (TNFα) Antagonist Failure Subpopulation [ Time Frame: Week 6 ]

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.

• Original Primary Outcome Measures (submitted: October 18, 2010): Proportion of patients in clinical remission in the tumor necrosis factor alpha antagonist therapy subpopulation [ Time Frame: Week 6 ]

Current Secondary Outcome Measures (submitted: June 19, 2014)

• Percentage of Participants in Clinical Remission at Week 6 in the Overall Population [ Time Frame: Week 6 ]
  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.
• Percentage of Participants in Clinical Remission at Week 10 in the TNFα Antagonist Failure Subpopulation [ Time Frame: Week 10 ]
  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.
• Percentage of Participants in Clinical Remission at Week 10 in the Overall Population [ Time Frame: Week 10 ]
  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.
• Percentage of Participants With Sustained Clinical Remission in the TNFα Antagonist Failure Population [ Time Frame: Week 6 and Week 10 ]
  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.
• Percentage of Participants With Sustained Clinical Remission in the Overall Population [ Time Frame: Week 6 and Week 10 ]
  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.
• Percentage of Participants With Enhanced Clinical Response at Week 6 in the TNFα Antagonist Failure Subpopulation [ Time Frame: Baseline and Week 6 ]
  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.
• Number of Participants With Adverse Events (AEs) [ Time Frame: 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. ]
  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?

Original Secondary Outcome Measures (submitted: October 18, 2010)

• Proportion of patients in clinical remission [ Time Frame: Week 6 and Week 10 ]
• Proportion of patients with sustained clinical remission [ Time Frame: Week 6 and Week 10 ]
• Proportion of patients with enhanced clinical response [ Time Frame: Week 6 ]
• Safety profile [ Time Frame: Through Week 22 ]
  Adverse events, serious adverse events, results of standard laboratory tests and results of 12-lead electrocardiograms (ECGs)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Vedolizumab in Patients With Moderate to Severe Crohn's Disease
• Official Title: 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
• Brief Summary: 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.

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Crohn's Disease

Intervention

• Drug: vedolizumab
  Vedolizumab for intravenous infusion
  Other Names:

  • Entyvio
  • MLN0002
  • MLN02
  • LDP-02
• Other: Placebo
  Placebo intravenous infusion

Study Arms

• Placebo Comparator: Placebo
  Participants received placebo intravenous infusion at Weeks 0, 2 and 6.
  Intervention: Other: Placebo
• Experimental: Vedolizumab
  Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
  Intervention: Drug: vedolizumab

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 6, 2012): 416
• Original Estimated Enrollment (submitted: October 18, 2010): 396
• Actual Study Completion Date: April 2012
• Actual Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States
• Removed Location Countries: Puerto Rico

Administrative Information

• NCT Number: NCT01224171
• Other Study ID Numbers: C13011; U1111-1158-2581 ( Registry Identifier: WHO ); 2009-016488-12 ( EudraCT Number ); NL34356.078.10 ( Registry Identifier: CCMO )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Millennium Pharmaceuticals, Inc.
• Original Responsible Party: Catherine Milch, M.D., Associate Medical Director, Millennium Pharmaceuticals
• Current Study Sponsor: Millennium Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Monitor; Millennium Pharmaceuticals, Inc.

• PRS Account: Millennium Pharmaceuticals, Inc.
• Verification Date: June 2014