Bavituximab Repeat-Dose Trial in Patients Co-Infected With Chronic Hepatitis C Virus and Human Immunodeficiency Virus

A Phase Ib Open-Label, Escalating Repeat-Dose Trial of Bavituximab (Chimeric Anti-Phosphatidylserine Monoclonal Antibody) in Patients Co-Infected With Chronic Hepatitis C Virus and Human Immunodeficiency Virus

This trial is designed to assess the safety, tolerability, pharmacokinetics and viral kinetics after multiple infusions of bavituximab in patients co-infected with HCV and HIV.

OBJECTIVES:

• To determine the safety and tolerability of bavituximab administered as multiple intravenous (IV) infusions to patients co-infected with HCV and HIV
• To characterize the pharmacokinetic profile and viral kinetics after multiple intravenous infusions of bavituximab to patients infected with HCV and HIV
• To define the maximum tolerated dose (MTD) and/or maximum effective dose (MED) of bavituximab administered as multiple infusions to patients infected with chronic HCV infection and HIV

Inclusion Criteria:

• Written informed consent has been obtained
• Adults 18 years of age or older
• HIV infection documented by detectable HIV RNA PCR
• Absolute CD4+ > 300 cells/mm3
• Chronic hepatitis C infection based on history and detectable serum HCV RNA
• Serum alanine aminotransferase (ALT) above normal limits and/or historical biopsy consistent with hepatitis C
• Complete blood counts within normal limits
• Normal renal function (serum creatinine within normal limits)
• PT/INR and aPTT within normal limits
• All patients of reproductive potential must agree to use an approved form of barrier contraception or agree not to become pregnant while taking study medications and for 30 days after study completion. Female patients must have a negative serum pregnancy test at prestudy (not applicable to patients with bilateral oophorectomy and/or hysterectomy or to those patients who are postmenopausal)

Exclusion Criteria:

• HCV or HIV antiviral therapy within 4 weeks of Day 0
• Prior exposure to any chimeric antibody
• Any other cause of liver disease other than chronic hepatitis C, such as autoimmune or alcoholic liver disease.
• Decompensated clinical liver disease, including a history of prolonged clotting times, hypoalbuminemia, encephalopathy, treatment for elevated ammonia levels, or ascites
• Any evidence of clinically significant bleeding defined as gross hematuria, hemoptysis, or gastrointestinal bleeding
• Known history of bleeding diathesis or coagulopathy (e.g., von Willebrand Disease or Hemophilia)
• Any history of thromboembolic events [e.g., deep vein thrombosis (DVT) or pulmonary thromboembolism (PE)]. A history of including central venous catheter-related thrombosis is acceptable if there is documentation of resolution at least 12 months prior to enrollment.
• Concurrent therapy with oral or parenteral anticoagulants
• Concurrent hormone therapy (i.e., estrogen contraceptives, hormone replacement, anti-estrogen)
• Investigational therapy within 4 weeks of Day 0
• Major surgery within 4 weeks of Day 0
• Pregnant or nursing women
• Uncontrolled intercurrent disease (e.g., diabetes, hypertension, thyroid disease)
• Any history of angina pectoris, coronary artery disease or cerebrovascular accident, or transient ischemic attack
• A history of any condition requiring anti-platelet therapy with the exception of general cardiovascular prophylaxis with aspirin
• A history of any condition requiring treatment (past or current) with coumarin-type agents
• Cardiac arrhythmia requiring medical therapy
• Serious non-healing wound (including wound healing by secondary intention, ulcer, or bone fracture)
• Requirement for chronic daily treatment with NSAIDs, antiplatelet drugs (e.g., phosphodiesterase inhibitors, adenosine diphosphate receptor antagonists), or steroids
• Cancer, autoimmune disease or any disease or concurrent therapy known to cause significant alteration in immunologic function. Corticosteroids administered as pre-treatment, or to treat an adverse event, are allowed.