ISIS 14803-CS2, Treatment With ISIS 14803, Administered IV in Patients With Chronic Hepatitis C Virus Infections

Inclusion criteria

Patients must meet the following inclusion criteria during screening:

• Age greater than or equal to 18 years.
• Both males and females are eligible. All patients should be advised that there are no data on the possible reproductive (teratological) effects of ISIS 14803.

Therefore:

• a) Females may participate if they are surgically sterile or post-menopausal. Pre-menopausal women may participate if they are abstinent or are compliant with a contraceptive regimen. Abstinence or contraceptive regimen must be maintained during the treatment period and for 4 weeks after discontinuation of therapy. A negative serum pregnancy test (i.e., human chorionic gonadotropin, hCG) within 2 weeks prior to dosing with ISIS 14803 is required for pre-menopausal women. Subjects must not be breast feeding.
• b) Male patients must be surgically sterile, abstinent, or utilizing a barrier contraceptive method. Abstinence or contraceptive regimen must be maintained during the treatment period and for 4 weeks after discontinuation of therapy.
• Anti-HCV antibody positive.
• Plasma HCV RNA greater than 10,000 copies/mL.
• Prior liver biopsy indicating chronic hepatitis.
• WBC count less than or equal to upper limit of normal.
• Absolute neutrophil count in normal range for the laboratory.
• Platelet count greater than 130,000 cells/mm³.
• Hemoglobin concentration greater than or equal to 11 g/dL.
• PT in the normal range for the laboratory.
• Normal aPTT.
• Bilirubin in the normal range unless due to documented Gilbert's disease.
• Serum creatinine less than or equal to 1.5 times the upper limit of the normal range.
• Urinalysis showing no evidence of infection or active renal disease (e.g., proteinuria).
• Subjects must be able to adhere to the visit schedule set forth in this protocol.
• Written informed consent prior to the performance of any study related procedures.

Exclusion criteria

Patients with any of the following criteria during screening will not be eligible:

• Human immunodeficiency virus (HIV) infection (Western immunoblot confirmed presence of anti-HIV antibodies or detection of HIV RNA in blood).
• Chronic hepatitis B virus (HBV) infection (HBV surface antigen or DNA in blood).
• Antiviral therapy for HCV within 3 months.
• Immunomodulatory therapy (e.g., systemic corticosteriods or interferon) within 3 months.
• Advanced or decompensated liver disease (e.g., history of bleeding varices, spontaneous hepatic encephalopathy, ascites) of any etiology such as alcohol, drug, obesity, or hemochromatosis.
• ALT greater than 5x ULN.
• Histologic evidence of cirrhosis.
• Presence of an underlying disease state associated with active bleeding.
• Undergoing therapeutic anticoagulation with heparin or warfarin.
• Presence of any other active infection requiring therapy.
• Presence of malignancy.
• Presence or history of any significant medical illness that might interfere with this study.
• Receipt of an investigational new drug, biological or therapeutic device within 30 days of study entry.
• Alcohol or drug abuse requiring medical intervention within 2 years.
• History of non-compliance with prescribed medical care.
• Limited mental capacity or language skills to the extent simple instructions cannot be followed or information regarding adverse events cannot be provided