Study of Visilizumab in Subjects With Intravenous Steroid-Refractory Ulcerative Colitis (IVSR-UC)

A Phase 2, Randomized, Double-blind, Multicenter, Dose-exploration Study of Visilizumab in Subjects With Intravenous Steroid-refractory Ulcerative Colitis

The purpose of this study is to assess the efficacy, immunogenicity, and safety of various doses of visilizumab in subjects with intravenous steroid-refractory ulcerative colitis (IVSR-UC) and to evaluate optimal dosing.

PDL BioPharma, Inc. was formerly known as Protein Design Labs, Inc.

Inclusion Criteria

Eligible subjects will be considered for inclusion in this study if they meet all of the following criteria:

• Males and females, 18 years of age or older.
• Diagnosis of ulcerative colitis (UC), as verified by endoscopy performed within 60 months prior to consent.
• Severe active disease, as defined by modified Truelove Witts severity index (MTWSI) >= 11 at consent, with a confirmatory MTWSI >= 10 on or after the fifth consecutive day of intravenous (IV) steroids and within 1 day prior to randomization.
• Mayo score >= 10 and Mayo mucosal subscore >= 2 after a minimum of 3 consecutive days (ie, on or after the fourth consecutive day) of IV steroids.
• Adequate contraception from the day of consent through 3 months after the last dose of study drug.
• Negative serum pregnancy test at screening.
• Negative Clostridium difficile test within 10 days prior to randomization.
• Signed and dated informed consent and Health Insurance Portability and Accountability Act (HIPAA) if applicable.

Exclusion Criteria

Subjects will be ineligible for this study if they meet any one of the following criteria:

• UC requiring immediate intervention.
• History of total proctocolectomy, or subtotal colectomy with ileorectal anastomosis
• Presence of ileostomy.
• White blood cell count less than 2.5 x 10^3/mcL; platelet count less than 150 x 10^3/mcL; or hemoglobin level less than 8 g/dL.
• Active medically significant infections, particularly those of viral etiology, eg, known cytomegalovirus (CMV) colitis. This includes any incidence of medically significant opportunistic infections within the past 12 months.
• Live vaccination within 6 weeks prior to randomization.
• Significant organ dysfunction, including cardiac, renal, liver, central nervous system (CNS), pulmonary, vascular, gastrointestinal, endocrine, or laboratory abnormality.
• History or treatment of lymphoproliferative disorder (LPD) or malignancy within the past 5 years (excluding nonmelanoma skin cancer or carcinoma in situ of the cervix).
• Seropositivity for infection with human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) surface antigen, or hepatitis C virus (HCV).
• Pregnancy or nursing.
• Treatment with a first dose of infliximab or another anti-TNF-a drug within 4 weeks of randomization, or treatment with a subsequent dose of an anti-TNF-a drug within 2 weeks of randomization.
• Treatment with cyclosporine or tacrolimus (FK506) within 2 weeks prior to randomization.
• Treatment with any other investigational drugs or therapies within 60 days prior to randomization, except those mentioned in the two exclusion criteria above.
• Unwilling or unable to discontinue all UC drugs, except glucocorticoids and oral 5-ASA, immediately prior to randomization.
• Nontherapeutic levels of chronic antiseizure medications in subjects with a prior history of seizures.
• Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation.