A Phase 2, Open Label Study of the Safety, Antiretroviral Activity and Pharmacokinetics of 3BNC117 During a Short Analytical Treatment Interruption in HIV-infected Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of Participants With Virologic Rebound at 8 Weeks After Interruption of Antiretroviral Therapy
研究概览
简要总结
This study evaluates the effects of two infusions of 3BNC117 in preventing or delaying rebound of viral load during a brief treatment interruption of standard ART and its safety during a brief analytical interruption of antiretroviral therapy.
详细描述
The proposed study is a Phase II, open label study to evaluate the safety and antiretroviral activity of two and four infusions of 3BNC117 in HIV-infected subjects on combination ART during a brief analytical treatment interruption.
After meeting enrollment criteria sixteen subjects with 3BNC117 sensitive virus (<2μg/ml IC50) will receive two (Group A) or four (Group B) intravenous infusions of 3BNC117, administered at 30 mg/kg.
In both dosing groups, antiretroviral therapy will be discontinued 2 days after the first 3BNC117 infusion (day 2) until week 12. Combination ART will be resumed at week 12. ART will be resumed sooner if plasma HIV-1 RNA level is ≥ 200 copies/ml or if CD4+ count drops < 350 cells/μl and either result is confirmed upon repeat measurement. Participants will be followed weekly until week 12 for safety assessments and for monitoring plasma HIV-1 RNA levels (viral load). CD4+ T cell counts will be monitored every 2 weeks until week 12.
Participants may remain off antiretroviral therapy after week 12, with weekly viral load monitoring, if viral rebound does not occur by week 12. Participants will be followed for a total of 36 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Age 18 to 65
- •HIV-1 infection confirmed by ELISA and immunoblot.
- •Plasma HIV-1 RNA < 50 copies/ml for at least 12 months while on combination ART and < 20 copies/ml at the screening visit. [Note: One or two viral blips of < 200 copies/mL prior to enrollment are permitted if preceded and followed by test results showing VL less than or equal to 50 copies/mL on the same ARV regimen.]
- •3BNC117 sensitivity (IC50 < 2 μg/ml) of subject derived HIV-1 virus isolates. These are isolated under protocol MCA-823 by co-culture of subject PBMCs with HIV-uninfected donor PBMCs followed by in vitro neutralization assays as previously described
- •Current CD4 cell count > 500 cells/μl and no prior CD4 cell count < 200 cells/μl.
- •Willing to interrupt antiretroviral treatment for 12 weeks, or until viral rebound occurs.
- •If sexually active male or female, and participating in sexual activity that could lead to pregnancy using an effective method of contraception throughout the study period. Subjects should also agree to use a male or female condom during the time of pausing their HIV medication.
- •If on an NNRTI-based regimen willing to a switch for 4 weeks to dolutegravir.
排除标准
- •Have a history of AIDS-defining illness within 1 year prior to enrollment
- •History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months;
- •Chronic hepatitis B or hepatitis C;
- •Patient report, or chart history, of significant coronary artery disease, myocardial infarction, percutaneous coronary intervention with placement of cardiac stents;
- •Patient report, or chart history, of diabetes type 1 or 2 and/or current use of insulin or oral hypoglycemic medications;
- •Uncontrolled hypertension, as defined by a systolic blood pressure > 180 and/or diastolic blood pressure > 120, in the presence or absence of anti-hypertensive medications;
- •Any other clinically significant acute or chronic medical condition, such as autoimmune diseases, that in the opinion of the investigator would preclude participation;
- •Current cigarette use in excess of 1 pack per day;
- •Laboratory abnormalities in the parameters listed below:
- •Absolute neutrophil count ≤1,000
- •Hemoglobin ≤ 10 gm/dL
- •Platelet count ≤125,000
- •ALT ≥ 2.0 x ULN
- •AST ≥ 2.0 x ULN
- •Total bilirubin ≥ 1.5 ULN
- •Creatinine ≥ 1.1 x ULN
- •Coagulation parameters ≥ 1.5 x ULN;
- •Current antiretroviral regimen includes either maraviroc or enfuvirtide;
- •Pregnancy or lactation;
- •Any vaccination within 14 days prior to 3BNC117 administration;
- •Receipt of any monoclonal antibody therapy of any kind in the past;
- •Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
- •History of resistance to two or more antiretroviral drug classes
研究组 & 干预措施
Group A: 3BNC117 IV + ART Interruption
Two intravenous infusions of 3BNC117 (30 mg/kg) at day 0 and day 21, with interruption of antiretroviral treatment (ART) at day 2.
干预措施: 3BNC117 (Drug)
Group A: 3BNC117 IV + ART Interruption
Two intravenous infusions of 3BNC117 (30 mg/kg) at day 0 and day 21, with interruption of antiretroviral treatment (ART) at day 2.
干预措施: ART Interruption (Other)
Group B: 3BNC117 IV + ART interruption
Four intravenous infusions of 3BNC117 (30 mg/kg) at day 0, day 14, day 28, and day 42 with interruption of antiretroviral treatment (ART) at day 2.
干预措施: 3BNC117 (Drug)
Group B: 3BNC117 IV + ART interruption
Four intravenous infusions of 3BNC117 (30 mg/kg) at day 0, day 14, day 28, and day 42 with interruption of antiretroviral treatment (ART) at day 2.
干预措施: ART Interruption (Other)
结局指标
主要结局
Number of Participants With Virologic Rebound at 8 Weeks After Interruption of Antiretroviral Therapy
时间窗: 8 weeks
Virologic rebound is defined as confirmed plasma HIV-1 RNA level \> 200 copies/ml in two separate occasions
The Rate of Signs, Symptoms and Laboratory Abnormalities After 3BNC117 Infusions
时间窗: 36 weeks
The percentage of participants who experienced adverse events (e.g. signs, symptoms and laboratory abnormalities) following 3BNC117 infusions.
次要结局
- The Plasma Level of 3BNC117 at the Time of Viral Rebound.(36 weeks)