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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Randomized, Active-Control Phase II Pilot Trial of Bavituximab Combined With Ribavirin for Initial Treatment of Chronic Hepatitis C Virus Genotype 1 Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Bavituximab
* Drug: Pegylated interferon (PEG-IFN)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bavituximab 3 mg/kg<br>Bavituximab 3 mg/kg given by intravenous (IV) infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks | Drug: Bavituximab<br>* Bavituximab 3 mg/kg given by intravenous (IV) infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks or Bavituximab 0.3 mg/kg given by IV infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks or<br>* Other names: Bavituxmab;|
| Experimental: Bavituximab 0.3 mg/kg<br>Bavituximab 0.3 mg/kg given by IV infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks | Drug: Bavituximab<br>* Bavituximab 3 mg/kg given by intravenous (IV) infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks or Bavituximab 0.3 mg/kg given by IV infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks or<br>* Other names: Bavituxmab;|
| Active Comparator: Pegylated interferon (PEG-IFN)<br>Pegylated interferon (PEG-IFN) alpha-2a 180 micrograms given by subcutaneous (SC) injection once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks | Drug: Pegylated interferon (PEG-IFN)<br>* Pegylated interferon (PEG-IFN) alpha-2a 180 micrograms given by subcutaneous (SC) injection once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal 75 kg) divided into twice-daily doses, for 12 weeks<br>* Other names: Pegasys;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Hepatitis C Virus RNA | The primary endpoint is the proportion of patients who show a greater or equal 2-log(10) IU reduction in HCV RNA level at Study Week 12 (early virological response, EVR). | 12 weeks |