Infliximab Treatment Along With Pegylated Interferon and Ribavirin in the Treatment of Hepatitis C

The aim of the study is to investigate in subjects receiving their first course of peg-interferon α-2b plus ribavirin therapy for chronic HCV infection (genotype 1) whether the addition of infliximab to a standard regimen of pegylated interferon α-2b in combination with ribavirin:

• increases the proportion of subjects attaining a sustained virological response SVR (undetectable blood Hepatitis C viral load 6 months after treatment)
• improves the safety profile compared to the same regimen without infliximab

Inclusion criteria

• Male or female subjects, >18 years of age with proven chronic (greater than 6 months) hepatitis C infection (genotype 1) who have never been treated with pegylated interferon α-2b and /or ribavirin.

Criteria for inclusion in this trial are as follows:

• Male or female, 18 years of age or older
• Positive HCV RNA, Genotype 1, treatment naïve (never received pegylated interferon and / or ribavirin)
• Evidence of chronic HCV infection for at least six months prior to screening
• Findings on liver biopsy within the past 36 months that are consistent with the presence of chronic hepatitis C infection.
• Negative hepatitis B surface antigen
• No evidence of hemochromatosis
• Hemoglobin ≥12 g/dL for females and ≥13 g/dL for males
• WBC ≥3.0 x 109/L and neutrophils ≥1.5 x 109/L
• Platelets ≥80 x109/L
• Direct Bilirubin WNL +/- 50% of central laboratory normal range. Total bilirubin ≤1.6.
• Albumin within normal limits
• Serum creatinine within normal limits.
• Serum thyroid stimulating hormone (TSH) levels within normal limits
• Men and women of childbearing potential must use two forms of adequate birth control measures for the duration of the study and should continue such precautions for 6 months after receiving the last infusion.
• Subjects with a history of mild depression may be considered for entry into this study.
• No history of latent or active TB.

Exclusion criteria

• Women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion and men with partners who are pregnant at baseline or intend to become pregnant within 6 months after the last infusion.
• Known allergy against infliximab, ribavirin, or pegylated interferon
• Decompensated liver disease characterized as decreased hepatic synthetic functioning with abnormal albumin and bilirubin levels, prolonged prothrombin time or complications including ascites or recent variceal bleeding
• have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidiomycosis (Valley Fever)
• History of autoimmune hepatitis or a history of poorly controlled autoimmune disease
• Use of other systemic anti-inflammatory medication except NSAIDs and low dose systemic steroids
• Previous treatment with monoclonal antibodies or antibody fragments
• History of receiving human/murine recombinant products or a known allergy to murine products
• Documentation of seropositive for human immunodeficiency virus (HIV)
• History of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results
• History of serious infections (e.g., hepatitis, pneumonia or pyelonephritis) in the previous 3 months
• Opportunistic infection within 6 months prior to screening
• History of lymphoproliferative disease
• Currently have any known malignancy or have a history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence
• Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease
• Treatment with any other therapeutic agent targeted at reducing TNF within 3 months of screening
• Presence of a transplanted solid organ
• Concomitant diagnosis or history of congestive heart failure