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 - ND

• Conditions: moderate to Severe Crhon`s Disease; MedDRA version: 13.1Level: LLTClassification code 10013099Term: Disease CrohnsSystem Organ Class: 10017947 - Gastrointestinal disorders

• Registration Number: EUCTR2009-016488-12-IT
• Lead Sponsor: MILLENNIUM PHARMACEUTICALS, INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05-18
• Last Update Posted: 12 May 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 396

Inclusion Criteria

1. Age 18 to 80. 2. Male or female patient who is voluntarily able to give informed consent.Female patients who: ? Are postmenopausal for at least 1 year before screening, OR ? Are surgically sterile, OR ? If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form (ICF) through 6 months after the last dose of study drug, OR agree to completely abstain from heterosexual intercourse. Male patients, even if surgically sterilized (ie, status postvasectomy), who: ? Agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, OR ? Agree to completely abstain from heterosexual intercourse. 4. Diagnosis of CD established at least 3 months before enrollment by clinical and endoscopic evidence and corroborated by a histopathology report. Cases of CD established at least 6 months before enrollment for which a histopathology report is not available will be considered based on the weight of the evidence supporting the diagnosis and excluding other potential diagnoses, and must be discussed with the sponsor’s (or designee’s) medical monitor on a case-by-case basis before enrollment. 5. Moderately to severely active CD as determined by a CDAI score of 220 to 400(see Section 15.1) within 7 days before enrollment and 1 of the following: a. CRP level > 2.87 mg/L during the Screening period, OR b. Ileocolonoscopy with photographic documentation of a minimum of 3 nonanastomotic ulcerations (each > 0.5 cm in diameter) or 10 aphthous ulcerations (involving a minimum of 10 contiguous cm of intestine) consistent with CD, within 4 months before enrollment, ORFecal calprotectin = 250 ?g/g stool during the Screening period in conjunction with computed tomography (CT) enterography, magnetic resonance (MR) enterography, contrast-enhanced small bowel radiography, or wireless capsule endoscopy revealing Crohn’s ulcerations (aphthae not sufficient), within 4 months before screening. (Patients with evidence of fixed stenosis or small bowel stenosis with prestenotic dilation should not be included.) 6. CD involvement of the ileum and/or colon, at a minimum. 7. Patients with extensive colitis or pancolitis of > 8 years duration or limited colitis of > 12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months before enrollment (may be performed during screening). 8. Patients with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age > 50 years, or other known risk factor must be up-todate on colorectal cancer surveillance (may be performed during screening).Demonstrated, over the previous 5-year period, an inadequate response to, loss of response to, or intolerance of at least 1of the following agents as defined below: ? Immunomodulators o Signs and symptoms of persistently active disease despite a history of at least one 8-week regimen of oral azathioprine (= 1.5 mg/kg) or 6-MP (= 0.75 mg/kg), OR o Signs and symptoms of persistently active disease despite a history of at least one 8-week regimen of methotrexate (= 12.5 mg/week), OR o History of intolerance of at least 1 immunomodulator (including, but not limited to, nausea/vomiting, abdominal pain, pancreatitis, liver function test abnormalities, lymphopenia, TPMT genetic mutation, infecti

Exclusion Criteria

1. Evidence of abdominal abscess during screening 2. Extensive colonic resection or subtotal or total colectomy 3. History of > 3 small bowel resections or diagnosis of short bowel syndrome4. Have received tube feeding, defined formula diets, or parenteral alimentation within 21 days before enrollment 5. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine 6. Within 30 days before enrollment, have received any of the following for the treatment of underlying disease: a. Nonbiologic therapies (eg, cyclosporine, thalidomide) other than those specifically listed in Section 6.2.1 b. A nonbiologic investigational therapy c. An approved nonbiologic therapy in an investigational protocol d. Adalimumab 7. Within 60 days before enrollment, have received any of the following: a. Infliximab b. Certolizumab pegol c. Any other investigational or approved biological agent, other than local administration for non-IBD conditions (eg, intra-ocular injections) 8. Any prior exposure to natalizumab, efalizumab, or rituximab 9. Use of topical (rectal) treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks before enrollment 10. Evidence of or treatment for C. difficile infection or other intestinal pathogen within 28 days before enrollment 11. Currently require or are anticipated to require major surgical intervention for CD (eg, bowel resection) during the study. (Minor surgical procedures to treat complications of CD [eg, fistulotomy] are acceptable.) 12. History or evidence of adenomatous colonic polyps that have not been removed 13. History or evidence of colonic mucosal dysplasia (vd protocollo v 1 16/09/2010)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the effect of vedolizumab induction treatment on clinical remission at Week 6 in the subgroup of patients defined as having failed tumor necrosis factor alpha (TNFa) antagonist therapy (TNFa subpopulation);Secondary Objective: To determine the effect of vedolizumab induction treatment on clinical remission at Week 6 in the entire study population To determine the effect of vedolizumab induction treatment on clinical remission at Week 10 in the TNF? subpopulation and in the entire study population To determine the effect of vedolizumab induction treatment on sustained clinical remission (ie, clinical remission at both Week 6 and Week 10) in the TNFa subpopulation and in the entire study population To determine the effect of vedolizumab induction treatment on enhanced clinical response at Week 6 in the TNF asubpopulation;Primary end point(s): Proportion of patients in clinical remission at Week 6 in the TNF alpha subpopulation