A Randomized, Active-Control Phase II Pilot Trial of Bavituximab Combined With Ribavirin for Initial Treatment of Chronic Hepatitis C Virus Genotype 1 Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Reduction in Hepatitis C Virus RNA
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Bavituximab (Drug)
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
干预措施: Bavituximab (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 to 75 kg) divided into twice-daily doses, for 12 weeks
干预措施: Pegylated interferon (PEG-IFN) (Drug)
结局指标
主要结局
Reduction in Hepatitis C Virus RNA
时间窗: 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).
次要结局
未报告次要终点