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

Study Overview
=================
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.

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

Conditions
-----------------
Crohn's Disease

Intervention / Treatment
-----------------
* Drug: vedolizumab
* Other: Placebo


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo intravenous infusion at Weeks 0, 2 and 6. | Other: Placebo<br>* Placebo intravenous infusion<br>|
| Experimental: Vedolizumab<br>Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6. | Drug: vedolizumab<br>* Vedolizumab for intravenous infusion<br>* Other names: 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. |