INCLUSION CRITERIA:
1. Must give written informed consent and any authorizations required by local law
2. Aged 18 to 65 years old, inclusive, at the time of informed consent.
3. Must have an established diagnosis of UC for greater than or equal to 6 months
4. Must have endoscopy (flexible sigmoidoscopy or colonoscopy if clinically indicated) with biopsy to confirm the diagnosis of UC
5. Must have greater than 20 cm of active disease at Screening endoscopy.
6. Must have active UC with Mayo Score/DAI of 6 to 13 points and moderate to severe disease on endoscopy (Mayo endoscopic score of at least 2) despite prior or concomitant treatment with corticosteroids, azathioprine, 6-mercaptopurine, or any combination thereof.
7. Colonoscopy within the past 5 years for extent of disease and to exclude polyps.
8. For subjects with UC for greater than 10 years, colonoscopy with appropriate biopsies within 1 year prior to Screening to exclude dysplasia and neoplasia.
9. If receiving corticosteroid treatment prior to Screening, subjects must be willing to maintain stable doses until Week 8.
10. Prior to screening, subjects must be taking stable doses of 6-mercaptopurine or azathioprine for 12 weeks, and be willing to maintain stable doses until Week 12.
11. If subjects are taking 5-aminosalicylic acid prior to screening, they must be willing to maintain stable doses until Week 12.
12. Subjects must be willing and able to comply with a 7-day UC symptom collection by IVRS telephone diary as assessed during the Screening period.
13. All male subjects and female subjects of child-bearing potential must be willing and able to practice effective birth control during the study and be willing and able to continue contraception for 1 month after their last dose of study treatment.
EXCLUSION CRITERIA:
1. Subjects with a diagnosis of indeterminate colitis or Crohn's disease.
2. Subjects with clinical findings suggestive of Crohn's disease, eg., fistulae or granulomas on biopsy.
3. Subjects with an imminent need for surgery.
4. Subjects with toxic megacolon.
5. Subjects with primary sclerosing cholangitis.
6. Any of the following abnormal laboratory results:
- ALT and AST greater than or equal to 2 times ULN
- Hemoglobin less than or equal to 9 g/dL
- WBC less than 3500 cells/mm(3)
- Lymphocyte count less than 1000 cells/microL
- Platelet count less than 100,00 cells/microL
7. Female subjects who are pregnant or who wish to become pregnant during the study, or who are lactating.
8. Subjects with know symptomatic colonic stricture.
9. Stool culture positive for enteric infection, including parasitic and C. difficile infection.
10. Subjects who are positive for HBsAg, HCV, or HIV at Screening
(Medical History)
11. Subjects with a history of malignant disease, including solid tumors and hematologic malignancies (except basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
12. Subjects with a history of depression and/or suicidal ideation.
13. History of severe allergic or anaphylactic reactions.
14. History of intolerance to acetaminophen (paracetamol) that would preclude its use during the study period.
15. Subjects with a history of colonic or small bowel obstruction or resection.
16. Subjects with a history of colonic or small bowel obstruction or resection.
17. History of any clinically significant cardiac disease (including cardiomyopathy, congestive heart failure or related risk factors), or endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (including untreated or unstable seizures), dermatologic, renal, and psychiatric or other major disease, as determined by the Investigator. This includes psychosis, schizophrenia, mania, or major psychiatric illness requiring pharmacological treatment. Patients with a clinical diagnosis of anorexia nervosa or bulimia nervosa are excluded from the study.
18. Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening.
19. Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) within 6 months prior to Screening.
20. History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to Screening.
(Treatment History)
21. Treatment with another study treatment or approved therapy for investigational uses within the 4 weeks prior to the first dose of study treatment.
22. Exposure to monoclonal antibodies, cytokines, growth factors, soluble receptors, other recombinant products, or fusion proteins within 8 weeks prior to Screening.
23. Treatment with anti-TNF agents within 12 weeks prior to Screening.
24. Treatment with methotrexate, cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 8 weeks prior to Screening.
25. Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) other than low dose aspirin within 4 weeks prior to Screening.
26. Use of oral antibiotics for any reason within 2 weeks prior to Screening.
27. Treatment with rectally administered corticosteroids or rectally administered medications containing 5-aminosalicylates within 2 weeks prior to Screening.
28. Use of antidiarrheal agents during the screening period (between Screening and Visit 1)
29. Previous participation in this study.
30. Previous treatment with interferon Beta or other interferon products.
(Miscellaneous)
31. Blood donation (1 unit or more) within 2 months prior to Screening.
32. Current enrollment in any other study treatment or disease study.
33. Inability to comply with study requirements.
34. Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment.
SUB STUDY
INCLUSION CRITERIA
You must be enrolled in the main protocol to participate in the substudy.
EXCLUSION CRITERIA
Platelet count less than 90,000 per milliliter
Prothrombin time International Normalized Ratio greater than 1.3 or partial thromboplastin time greater than 3 seconds control.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009