Pilot Trial of Bavituximab Combined With Ribavirin for Initial Treatment of Chronic HepC Virus Genotype 1 Infection

Primary Objective: The primary objective of this study is to assess the effect of 12 weeks of initial treatment with bavituximab versus PEG-IFN, each combined with ribavirin, on plasma HCV RNA level in patients with chronic HCV genotype 1 infection.

Inclusion criteria

• Male or female between the ages of 18 and 65 years
• Chronic hepatitis C virus (HCV) genotype 1 infection
• HCV RNA level >10,000 IU/mL
• Chronic HCV infection, defined as:

• Previous documentation of positive HCV serology (HCV antibody or RNA) at least 6 months (24 weeks) previously, or
• Positive HCV serology (HCV antibody or RNA) with a prior remote (more than 6 months previously) risk factor for acquisition of HCV or
• Historical biopsy consistent with chronic HCV infection
• No clinically significant abnormalities in hematology, coagulation, or chemistry variables:

• Hemoglobin >12 g/dL for women; >13 g/dL for men
• Total white cell count >3000/mm3 and absolute neutrophil count >1500/mm3
• Platelets >100,000/mm3
• Prothrombin time (PT) and/or international normalized ratio (INR) less than or equal to 1.2 times the local upper limit of normal (ULN)
• Conjugated (direct) bilirubin less than or equal to 1.5 times the ULN
• Serum creatinine within normal limits
• Thyroid-stimulating hormone (TSH) and free thyroxine (T4) within normal limits
• Female patients: negative urine pregnancy test
• Ability to provide informed consent

Exclusion criteria

• Previous interferon-based antiviral therapy for chronic HCV infection
• Previous treatment with known immunogenic drugs
• Concomitant human immunodeficiency (HIV) or hepatitis B virus (HBV) infection
• Cause of liver disease other than chronic HCV infection, such as autoimmune or alcoholic liver disease
• Decompensated clinical liver disease, including a history of encephalopathy, bleeding esophageal or gastric varices, or ascites
• Recipient of liver or other solid-organ transplantation
• Evidence of clinically significant bleeding, defined as gross hematuria, hemoptysis, or gastrointestinal bleeding
• History of bleeding diathesis or coagulopathy (eg, von Willebrand disease or hemophilia)
• History of thromboembolic events (eg, deep-vein thrombosis [DVT] or pulmonary embolism). Previous central venous catheter-related thrombosis is acceptable if there is resolution recorded at least 12 months before enrollment.
• Requirement for concurrent treatment with oral or parenteral anticoagulants or hormones (estrogen-containing contraceptives, hormone replacement, antiestrogen agents, progestins)
• Condition requiring daily therapy with antiplatelet agents (eg, thienopyridines, dipyridamole, cilostazol; cardiovascular prophylaxis with aspirin is allowed) or corticosteroids
• Investigational therapy within 28 days before the first planned dose of study drug
• Major surgery within 28 days before the first planned dose of study drug
• Uncontrolled intercurrent disease (eg, diabetes, hypertension, thyroid disease)
• Ongoing angina pectoris or other symptoms of coronary artery disease (CAD); history of stroke, or transient ischemic attack (TIA)
• History of suicidal ideation or attempt
• Condition requiring treatment (past or current) with coumarin-type agents
• Cardiac arrhythmia requiring medical therapy
• Serious nonhealing wound (including wound healing by secondary intention, ulcer, or bone fracture)
• Cancer, autoimmune disease, or any disease or concurrent therapy known to cause significant alteration in immune function (corticosteroids are allowed before study enrollment and during the study to treat an AE)
• Female patients and female partners of male patients: pregnancy, lactation, or inability/unwillingness to practice effective contraception