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Study of Vedolizumab in Patients With Moderate to Severe Crohn's Disease

Phase 3
Completed
Conditions
Crohn's Disease
Interventions
Other: Placebo
Drug: vedolizumab
Registration Number
NCT01224171
Lead Sponsor
Millennium Pharmaceuticals, Inc.
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
416
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
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Exclusion Criteria

Not provided

Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants received placebo intravenous infusion at Weeks 0, 2 and 6.
VedolizumabvedolizumabParticipants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants in Clinical Remission in the Tumor Necrosis Factor Alpha (TNFα) Antagonist Failure SubpopulationWeek 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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Sustained Clinical Remission in the Overall PopulationWeek 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 SubpopulationBaseline 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.

Percentage of Participants in Clinical Remission at Week 6 in the Overall PopulationWeek 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 SubpopulationWeek 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 PopulationWeek 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 PopulationWeek 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.

Number of Participants With Adverse Events (AEs)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?

Trial Locations

Locations (41)

Atlanta Gastroenterology Associates

🇺🇸

Atlanta, Georgia, United States

University of Kentucky Medical Center

🇺🇸

Lexington, Kentucky, United States

Gastroenterology of the Rockies

🇺🇸

Lafayette, Colorado, United States

Gastroenterology Center of Connecticut P.C.

🇺🇸

Hamden, Connecticut, United States

University of Florida

🇺🇸

Gainesville, Florida, United States

Shafran Gastroenterology Center

🇺🇸

Winter Park, Florida, United States

Gastroenterology Associates of Central Georgia

🇺🇸

Macon, Georgia, United States

Atlanta Gastroenterology Specialist PC

🇺🇸

Suwanee, Georgia, United States

University of Chicago Medical Center

🇺🇸

Chicago, Illinois, United States

University Of Louisville

🇺🇸

Louisville, Kentucky, United States

Gastroenterology Associates

🇺🇸

Baton Rouge, Louisiana, United States

Gastroenterology Research of New Orleans

🇺🇸

Hammond, Louisiana, United States

Metropolitan Gastroenterology Group P.C.

🇺🇸

Chevy Chase, Maryland, United States

Mid-Atlantic Medical Research Center

🇺🇸

Hollywood, Maryland, United States

Massachusetts General Hospital Crohn's and Colitis Center

🇺🇸

Boston, Massachusetts, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Center for Digestive Health

🇺🇸

Troy, Michigan, United States

Huron Gastroenterology Associates

🇺🇸

Ypsilanti, Michigan, United States

Minnesota Gastroenterology P.A.

🇺🇸

Plymouth, Minnesota, United States

Washington University

🇺🇸

St. Louis, Missouri, United States

Long Island Clinical Research Associates

🇺🇸

Great Neck, New York, United States

Dartmouth-Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Options Health Research

🇺🇸

Tulsa, Oklahoma, United States

Charlotte Gastroenterology and Hepatology P.L.L.C

🇺🇸

Charlotte, North Carolina, United States

Consultants in Gastroenterology

🇺🇸

Columbia, South Carolina, United States

Gastroenterology Center of the MidSouth PC

🇺🇸

Germantown, Tennessee, United States

Digestive Health Specialists of Tyler

🇺🇸

Tyler, Texas, United States

University of Virginia Health System

🇺🇸

Charlottesville, Virginia, United States

Cotton O'Neil Digestive Health Center

🇺🇸

Topeka, Kansas, United States

University of Rochester

🇺🇸

Rochester, New York, United States

New York Presbyterian Hospital

🇺🇸

New York, New York, United States

Zeidler Ledcor Center-Univerisity of Alberta

🇨🇦

Edmonton, Alberta, Canada

University of Miami Miller School of Medicine

🇺🇸

Miami, Florida, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Consultants for Clinical Research Inc.

🇺🇸

Cincinnati, Ohio, United States

The Oregon Clinic-West Hills Gastroenterology

🇺🇸

Portland, Oregon, United States

Gastroenterology Clinic of San Antonio

🇺🇸

San Antonio, Texas, United States

University of Washington School of Medicine

🇺🇸

Seattle, Washington, United States

Wisconsin Center for Advanced Research

🇺🇸

Milwaukee, Wisconsin, United States

Medical College Of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

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