A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab (MLN0002) in Patients with Moderate to Severe Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 11 September 2012
• Main ID: EUCTR2008-002783-33-MT
• Date of registration: 25/11/2008
• Prospective Registration: Yes
• Primary sponsor: Millennium Pharmaceuticals, Inc.
• Public title: A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab (MLN0002) in Patients with Moderate to Severe Ulcerative Colitis
• Scientific title: A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab (MLN0002) in Patients with Moderate to Severe Ulcerative Colitis
• Date of first enrolment: 28/01/2009
• Target sample size: 1060
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-002783-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: yes Parallel group: yes Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, Bulgaria, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Malta, Netherlands, Portugal, Slovakia, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age 18 to 80

2. Male or female patient voluntarily able to give informed consent

3. Female patients must:
• be post-menopausal for at least 1 year before the screening visit, OR
• be 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 through 6 months after the last dose of study drug, OR
• agree to completely abstain from heterosexual contact.
Male patients, even if surgically sterilized (ie, status post-vasectomy), must:
• 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 contact.

4. Diagnosis of Crohn’s disease established at least 6 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report. Cases of Crohn’s disease established at least 12 months prior to enrollment for which a histopathology report is not available will be considered.

5. Moderate to severe CD as determined by CDAI score of 220 to 480 within 7 days of first administration of study drug 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 non-anastomotic ulcerations (each >0.5 cm in diameter, aphthous ulcerations not sufficient) consistent with CD within 4 months prior to screening

6. CD involvement of the ileum and/or colon, at a minimum

7. Patients with extensive colitis or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have evidence of a surveillance colonoscopy within 12 months of initial screening visit.

8. Patients with family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance.

9. Over the previous 5 year period, an inadequate response to, loss of reponse to, or intolerance of at least one of the following agents as defined below:
• Corticosteroids,
Symptoms of persistently active disease despite a history of at least one 4-week induction regimen that included a dose equivalent to prednisone 30 mg daily orally for 2 weeks or intravenously for 1 week OR Two failed attempts to taper corticosteroids to below a dose equivalent to prednisone 10 mg daily orally on two separate occasions OR History of intolerance of corticosteroids (including Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection)
• Immunomodulators
Symptoms of persistently active disease despite history of at least one 8 week regimen of oral azathioprine (=1.5 mg/kg) or 6-mercaptopurine mg/kg (=0.75 mg/kg) OR Symptoms of persistently active disease despite a history of at least one 8 week regimen of methotrexate (=12.5 mg/week) OR History of intolerance of at least one immunomodulator (including nausea/vomiting, abdominal pain, pancreatitis, LFT abnormalities, lymphopenia, TPMT genetic mutation, infection)

• TNF antagonists
Symptoms of persistently active disease despite history of at least one 4 week induction regimen of one of the following agents:
Infliximab 5 mg/kg IV, 2 doses at least 2 weeks apart
Adalimumab one 80 mg SC dose followed by one 40 mg dose at least 2 weeks apart
Certolizumab pegol 400 mg SC, 2 doses at least 2 weeks apart OR
Recurrence of symptoms during s
Exclusion criteria:
Gastrointestinal Exclusion Criteria
1. Evidence of abdominal abscess at the initial screening visit
2. Extensive colonic resection, subtotal or total colectomy
3. History of >3 small bowel resections or diagnosis of short bowel syndrome
4. Have received tube feeding, defined formula diets, or parenteral alimentation within 21 days prior to the administration of the first dose of study drug
5. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
6. Within 30 days prior to enrollment, have received any of the following for the treatment of underlying disease:
a) Non-biologic therapies (eg, cyclosporine, thalidomide) other than those permitted
b) A non-biologic investigational therapy
c)An approved non-biologic therapy in an investigational protocol
7. Within 60 days prior to enrollment, have received any of the following:
a) Infliximab, adalimumab, or certolizumab pegol
b)Other investigational or approved biological agent
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 of the administration of the first dose of study drug
10. Evidence of or treatment for C. difficile infection within 60 days or other intestinal pathogen within 30 days prior to enrollment
11. Currently require or are anticipated to require surgical intervention for CD during the study
12. History or evidence of adenomatous colonic polyps that have not been removed
13. History or evidence of colonic mucosal dysplasia
14. Diagnosis of ulcerative colitis or indeterminate colitis
Infectious Disease Exclusion Criteria
1. Any chronic hepatitis B or C infection
2. Active or latent tuberculosis, regardless of treatment history, as evidenced by any of the following:
a) History of tuberculosis
b) A positive diagnostic tuberculosis (TB) test within one month of enrollment defined as:
i) a positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests OR
ii)a tuberculin skin test reaction = 10 mm (= 5 mm in patients receiving the equivalent of > 15 mg/day prednisone).
c) Chest x-ray within 3 months of enrollment in which active or latent pulmonary tuberculosis cannot be excluded
3. Any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation)
4. Any live vaccinations within 30 days prior to study drug administration except for the influenza vaccine
5. Clinically significant extra-intestinal infection (eg, pneumonia, pyelonephritis) within 30 days of the initial screening visit
General Exclusion Criteria
1. Previous exposure to MLN0002
2. Female patients who are lactating or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 prior to study drug administration.
3. Any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise patient safety
4. Had any surgical procedure requiring general anesthesia within 30 days prior to enrollment or is planning to undergo surgery during the study period
5. Any history of malignancy, except for the following:
• adequately-treated non-metastatic basal cell skin cancer;
• Squamous cell skin cancer that has been adequately tr

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate to Severe Crohn's Disease
MedDRA version: 9.1 Level: LLT Classification code 10013099 Term: Disease Crohns

Intervention(s)

Product Name: VEDOLIZUMAB
Product Code: MLN0002
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: VEDOLIZUMAB
CAS Number: 943609-66-3
Current Sponsor code: MLN0002
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300mg-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: Primary Objective for the Induction Phase

• To determine the effect of MLN0002 induction treatment on clinical remission at 6 weeks

Primary Objective for the Maintenance Phase

• To determine the effect of MLN0002 maintenance treatment on clinical remission at 52 weeks

Primary end point(s): Primary Endpoint for the Induction Phase

• Proportion of patients in clinical remission at Week 6


Primary Endpoint for the Maintenance Phase

• Proportion of patients in clinical remission at Week 52

Secondary Objective: Secondary Objectives for the Induction Phase

• To determine the effect of MLN0002 induction treatment on enhanced clinical response at 6 weeks

• To determine the effect of MLN0002 induction treatment on serum C-reactive protein (CRP) levels at 6 weeks in patients with elevated CRP levels at baseline



Secondary Objectives for the Maintenance Phase

• To determine the effect of MLN0002 maintenance treatment on enhanced clinical response at 52 weeks

• To determine the effect of MLN0002 maintenance treatment on corticosteroid-free remission at 52 weeks

• To determine the effect of MLN0002 maintenance treatment on durability of clinical remission over 52 weeks

Secondary ID(s)

C13007

2008-002783-33-ES