Pilot Trial of Bavituximab Combined With Ribavirin for Initial Treatment of Chronic HepC Virus Genotype 1 Infection
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Bavituximab 3 mg/kg 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
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
Other Names:
|
| Experimental: Bavituximab 0.3 mg/kg 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
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
Other Names:
|
| Active Comparator: Pegylated interferon (PEG-IFN) 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)
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
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Reduction in Hepatitis C Virus RNA [12 weeks]
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).
Eligibility Criteria
Criteria
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:
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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
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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
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Decompensated clinical liver disease, including a history of encephalopathy, bleeding esophageal or gastric varices, or ascites
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Recipient of liver or other solid-organ transplantation
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Evidence of clinically significant bleeding, defined as gross hematuria, hemoptysis, or gastrointestinal bleeding
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History of bleeding diathesis or coagulopathy (eg, von Willebrand disease or hemophilia)
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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.
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Requirement for concurrent treatment with oral or parenteral anticoagulants or hormones (estrogen-containing contraceptives, hormone replacement, antiestrogen agents, progestins)
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Condition requiring daily therapy with antiplatelet agents (eg, thienopyridines, dipyridamole, cilostazol; cardiovascular prophylaxis with aspirin is allowed) or corticosteroids
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Investigational therapy within 28 days before the first planned dose of study drug
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Major surgery within 28 days before the first planned dose of study drug
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Uncontrolled intercurrent disease (eg, diabetes, hypertension, thyroid disease)
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | LTD Vakhtang Bochorishvili Anticeptic Centre | Tbilisi | Georgia |
Sponsors and Collaborators
- Peregrine Pharmaceuticals
Investigators
- Study Chair: Janet Nuttall, MPH, Peregrine Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PPHM 1003