A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients with Moderate to Severe Ulcerative Colitis Estudio multicéntrico, ciego, controlado con placebo, aleatorizado, de fase 3, sobre la inducción y el mantenimiento de la respuesta clínica y la remisión con MLN0002, en pacientes con colitis ulcerosa moderada o grave

• Register: EUCTR
• Last refreshed on: 28 August 2014
• Main ID: EUCTR2008-002782-32-ES
• Date of registration: 23/10/2008
• 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 MLN0002 in Patients with Moderate to Severe Ulcerative Colitis Estudio multicéntrico, ciego, controlado con placebo, aleatorizado, de fase 3, sobre la inducción y el mantenimiento de la respuesta clínica y la remisión con MLN0002, en pacientes con colitis ulcerosa moderada o grave
• Scientific title: A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients with Moderate to Severe Ulcerative Colitis Estudio multicéntrico, ciego, controlado con placebo, aleatorizado, de fase 3, sobre la inducción y el mantenimiento de la respuesta clínica y la remisión con MLN0002, en pacientes con colitis ulcerosa moderada o grave
• Date of first enrolment: 02/03/2009
• Target sample size: 826
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-002782-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no 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, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age 18 to 80

2. Male or female patient who is 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 four weeks before the first dose of study drug 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 ulcerative colitis established at least 6 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report.

5. Moderate to severe ulcerative colitis as determined by a Mayo score of 6 to 12 with an endoscopic subscore ?2 during the screening period

6. Evidence of ulcerative colitis extending proximal to the rectum (?15 cm of involved colon)

7. Patients with extensive colitis or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence of a surveillance colonoscopy within 12 months of the initial screening visit (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-to-date on colorectal cancer surveillance (may be performed during screening)

9. Demonstrated, 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

i) Signs and 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
ii) Recurrence of clinical symptoms upon tapering below a dose equivalent to prednisone 10 mg daily orally on two separate occasions OR
iii) History of intolerance of corticosteroids (including, but not limited to Cushing?s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection)
? Immunomodulators
i) 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-mercaptopurine mg/kg (?0.75 mg/kg) OR
ii) History of intolerance of at least one immunomodulator (including, but not limited to nausea/vomiting, abdominal pain, pancreatitis, LFT abnormalities, lymphopenia, TPMT genetic mutation, infection)
? TNF antagonists
i) Signs and symptoms of persistently active disease despite a history of at
least one 4 week induction regimen of infliximab 5 mg/kg IV, 2 doses at
least 2 weeks apart OR
ii) Recurrence of symptoms during maintenance dosing following prior
clinical benefit (discontinuation despite clinical benefit does not qualify)
OR
iii) History of intolerance of infliximab (including, but not limited to infusionrelated
reaction, demyelination, congestive heart failure, infection)

10. May be receiving a therapeutic dose of the following drugs:
? Oral 5-ASA compounds provided that the dose has been stable for the 2 weeks immediately prior to enrollment
? Oral corticosteroid therap
Exclusion criteria:
The exclusion criteria are divided into 3 categories: gastrointestinal exclusion criteria, infectious disease exclusion criteria, and general exclusion criteria. Patients meeting any of the following exclusion criteria are not to be enrolled in the study.

Gastrointestinal Exclusion Criteria

1. Evidence of abdominal abscess or toxic megacolon at the initial screening visit

2. Extensive colonic resection, subtotal or total colectomy

3. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine

4. Within 30 days prior to enrollment, have received any of the following for the treatment of underlying disease:
? Non-biologic therapies (eg, cyclosporine, thalidomide) other than those
permitted in Section 6.2
? A non-biologic investigational therapy
? An approved non-biologic therapy in an investigational protocol

5. Within 90 days prior to enrollment, have received any of the following:
? Infliximab
? Other investigational or approved biological agent

6. Any prior exposure to natalizumab or rituximab

7. 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

8. Evidence of or treatment for C. difficile infection within 60 days or other intestinal pathogen within 30 days prior to enrollment

9. Currently require or are anticipated to require surgical intervention for UC during the study

10. History or evidence of adenomatous colonic polyps that have not been removed

11. History or evidence of colonic mucosal dysplasia

12. Diagnosis of Crohn?s 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:
? History of tuberculosis
? 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).
? 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 prior to enrollment

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;
? any other type of non-m

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

Health Condition(s) or Problem(s) studied

Moderate to Severe Ulcerative Colitis Colitis ulcerosa moderada o grave
MedDRA version: 9.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis

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: 300-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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

? Proportion of patients with clinical response at Week 6


Primary Endpoint for the Maintenance Phase:

? Proportion of patients in clinical remission at Week 52

Main Objective: Primary Objective for the Induction Phase

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

Primary Objective for the Maintenance Phase

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

Secondary Objective: Secondary Objectives for the Induction Phase

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

? To determine the effect of MLN0002 induction treatment on mucosal healing at 6 weeks


Secondary Objectives for the Maintenance Phase

? To determine the effect of MLN0002 maintenance treatment on durability of clinical response

? To determine the effect of MLN0002 maintenance treatment on mucosal healing at 52 weeks

? To determine the effect of MLN0002 maintenance treatment on durability of clinical remission

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

Secondary ID(s)

C13006