Pilot Trial of Bavituximab Combined With Ribavirin for Initial Treatment of Chronic HepC Virus Genotype 1 Infection
Pilot Trial of Bavituximab Combined With Ribavirin for Initial Treatment of Chronic HepC Virus Genotype 1 Infection
This will be a randomized, open-label, active-control Phase II pilot trial of bavituximab
 combined with ribavirin for initial treatment of chronic HCV genotype 1 infection. Eligible
 patients with normal coagulation, hematological, and renal function will undergo a
 screening/washout period of up to 28 days, followed by randomization to receive weekly
 bavituximab or PEG-IFN alpha-2a therapy for 12 weeks, both with twice-daily ribavirin.

 The primary endpoint of this study is the proportion of patients who show a greater than or
 equal to 2-log10 IU reduction in plasma HCV RNA level after 12 weeks of treatment (early
 virological response; EVR).

 Secondary endpoints include the proportion of patients with an undetectable HCV RNA level
 after 12 weeks of treatment; the proportion of patients who show a reduction in HCV RNA level
 of greater than or equal to 2 log10 IU after 4 weeks of treatment, viral kinetics for
 individual patients over time, and comprehensive evaluation of the safety and tolerability of
 bavituximab infusion.
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:

 1. Male or female between the ages of 18 and 65 years

 2. Chronic hepatitis C virus (HCV) genotype 1 infection

 3. HCV RNA level >10,000 IU/mL

 4. 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

 5. 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

 6. Female patients: negative urine pregnancy test

 7. Ability to provide informed consent

 Exclusion Criteria:

 1. Previous interferon-based antiviral therapy for chronic HCV infection

 2. Previous treatment with known immunogenic drugs

 3. Concomitant human immunodeficiency (HIV) or hepatitis B virus (HBV) infection

 4. Cause of liver disease other than chronic HCV infection, such as autoimmune or
 alcoholic liver disease

 5. Decompensated clinical liver disease, including a history of encephalopathy, bleeding
 esophageal or gastric varices, or ascites

 6. Recipient of liver or other solid-organ transplantation

 7. Evidence of clinically significant bleeding, defined as gross hematuria, hemoptysis,
 or gastrointestinal bleeding

 8. History of bleeding diathesis or coagulopathy (eg, von Willebrand disease or
 hemophilia)

 9. 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.

 10. Requirement for concurrent treatment with oral or parenteral anticoagulants or
 hormones (estrogen-containing contraceptives, hormone replacement, antiestrogen
 agents, progestins)

 11. Condition requiring daily therapy with antiplatelet agents (eg, thienopyridines,
 dipyridamole, cilostazol; cardiovascular prophylaxis with aspirin is allowed) or
 corticosteroids

 12. Investigational therapy within 28 days before the first planned dose of study drug

 13. Major surgery within 28 days before the first planned dose of study drug

 14. Uncontrolled intercurrent disease (eg, diabetes, hypertension, thyroid disease)

 15. Ongoing angina pectoris or other symptoms of coronary artery disease (CAD); history of
 stroke, or transient ischemic attack (TIA)

 16. History of suicidal ideation or attempt

 17. Condition requiring treatment (past or current) with coumarin-type agents

 18. Cardiac arrhythmia requiring medical therapy

 19. Serious nonhealing wound (including wound healing by secondary intention, ulcer, or
 bone fracture)

 20. 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)

 21. Female patients and female partners of male patients: pregnancy, lactation, or
 inability/unwillingness to practice effective contraception