Study of Visilizumab Versus Placebo in Subjects With Intravenous Steroid-refractory Ulcerative Colitis Previously Responsive in a Visilizumab Study

A Randomized, Double-blind, Multicenter Study of Visilizumab Versus Placebo in Subjects With Intravenous Steroid-refractory Ulcerative Colitis Previously Responsive in a Visilizumab Study

The purpose of this study is to compare the efficacy, safety, pharmacokinetics, and immunogenicity in subjects retreated with visilizumab or placebo after a response in a prior visilizumab study.

The purpose of this study is to compare the efficacy, safety, pharmacokinetics, and immunogenicity in subjects retreated with visilizumab or placebo after a response in a prior visilizumab study.

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

Inclusion Criteria:

• Males and females, 18 years of age or older.
• Only 1 prior treatment course with visilizumab (or placebo in a blinded visilizumab study).
• Response (as defined in parent protocol) of intravenous steroid-refractory ulcerative colitis (IVSR-UC) disease to visilizumab or placebo.
• Symptomatic worsening (ie, an increase of ≥3 points in MTWSI score) from the subject's best response on the parent study, an MTWSI score of ≥9, sustained for at least 2 assessments performed at least 1 week apart, and a confirmatory MTWSI ≥8 within 1 day prior to randomization.
• CD4^+ T-cell count ≥ 200 cells/mcL at screening for this protocol, or ≥ 80% of the subject's screening baseline count prior to enrollment on the parent study.
• Mayo assessment (including flexible sigmoidoscopy) performed by a trained, blinded evaluating physician within 2 weeks prior to randomization.
• Adequate contraception from the day of consent through 3 months after the last dose of study drug.
• Negative serum pregnancy test.
• Negative Clostridium difficile test.
• Signed and dated informed consent, and Health Insurance Portability and Accountability Act (HIPAA) if applicable.

Exclusion Criteria:

• UC requiring immediate surgical, endoscopic, or radiologic interventions.
• White blood cell count less than 2.5 x 10^3/mcL; platelet count less than 150 x 10^3/mcL; or hemoglobin less than 8 g/dL.
• Active, medically significant infections, particularly those of viral etiology, eg, known cytomegalovirus (CMV) colitis. This includes any incidence of opportunistic infections within the past 12 months.
• Live vaccination within 6 weeks prior to randomization.
• Significant organ dysfunction, including cardiac, renal, liver, CNS, pulmonary, vascular, gastrointestinal, endocrine, or laboratory abnormality, history of myocardial infarction, coronary artery disease, congestive heart failure, or arrhythmias within 6 months prior to consent.
• History of lymphoproliferative disorder (LPD) or malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix that has been adequately treated within the past five years.
• Seropositive for infection with human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) surface antigen, or hepatitis C virus (HCV).
• Pregnancy or nursing.
• Treatment with any other UC salvage drugs (including but not limited to infliximab or another anti-TNF-a drug, cyclosporine, tacrolimus [FK506], adalimumab, thalidomide, or another experimental agent), or therapies (surgery, pheresis, affinity columns) since the first course of treatment with study drug in the parent visilizumab study.
• Treatment with any other investigational drug or therapy within 60 days prior to randomization.
• Nontherapeutic levels of chronic antiseizure medications in subjects with a history of seizures.
• Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation.