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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01224171
First received: October 18, 2010
Last updated: June 19, 2014
Last verified: June 2014

October 18, 2010
June 19, 2014
November 2010
February 2012   (final data collection date for primary outcome measure)
Percentage of Participants in Clinical Remission in the Tumor Necrosis Factor Alpha (TNFα) Antagonist Failure Subpopulation [ Time Frame: Week 6 ] [ Designated as safety issue: No ]

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.

Proportion of patients in clinical remission in the tumor necrosis factor alpha antagonist therapy subpopulation [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01224171 on ClinicalTrials.gov Archive Site
  • Percentage of Participants in Clinical Remission at Week 6 in the Overall Population [ Time Frame: Week 6 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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. ] [ Designated as safety issue: Yes ]

    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?

  • Proportion of patients in clinical remission [ Time Frame: Week 6 and Week 10 ] [ Designated as safety issue: No ]
  • Proportion of patients with sustained clinical remission [ Time Frame: Week 6 and Week 10 ] [ Designated as safety issue: No ]
  • Proportion of patients with enhanced clinical response [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Safety profile [ Time Frame: Through Week 22 ] [ Designated as safety issue: Yes ]
    Adverse events, serious adverse events, results of standard laboratory tests and results of 12-lead electrocardiograms (ECGs)
Not Provided
Not Provided
 
Study of Vedolizumab in Patients With Moderate to Severe Crohn's Disease
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Crohn's Disease
  • Drug: vedolizumab
    Vedolizumab for intravenous infusion
    Other Names:
    • Entyvio
    • MLN0002
    • MLN02
    • LDP-02
  • Other: Placebo
    Placebo intravenous infusion
  • 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
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
416
April 2012
February 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01224171
C13011, U1111-1158-2581, 2009-016488-12, NL34356.078.10
Yes
Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
Not Provided
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP