A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117 Monoclonal Antibody in HIV-infected and HIV-uninfected Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 4
- 主要终点
- Safety and tolerability
研究概览
简要总结
The proposed study is a first-in-man phase I study that aims to evaluate the safety, tolerability and pharmacokinetics of 3BNC117 in HIV-infected and HIV-uninfected subjects, and its antiretroviral activity in HIV-infected subjects.
详细描述
In preclinical studies carried out in humanized mice and non-human primates, 3BNC117 alone or in combination with other neutralizing antibodies led to protection from HIV-1 or SHIV infection and also to sustained suppression of HIV-1 plasma viremia. The aims of this protocol are to evaluate the safety, tolerability and pharmacokinetics profile of 3BNC117 in both HIV-infected and HIV-uninfected subjects,and its antiretroviral activity in HIV-infected subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- 是
入选标准
- •Group 1 (HIV-uninfected):
- •Adult males and females, age 18 to 65
- •Amenable to HIV risk reduction counseling and agrees to maintaining behavior consistent with low risk of HIV exposure;
- •If a sexually active male or female, participating in sexual activity that could lead to pregnancy, agrees to use an effective method of contraception throughout the study.
- •Groups 2-5 (HIV-infected):
- •Age 18 to 65
- •HIV infection confirmed by ELISA and immunoblot
- •Groups 2A-D - on ART with HIV-1 plasma RNA levels below 100,000 copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA level between 2,000-100,000 copies/ml by standard assays on 2 occasions at least 1 week apart;
- •Group 2E - Untreated HIV-infected (not on ART for at least 8 weeks): HIV-1 RNA plasma levels between 2,000 - 100,000 copies/ml;
- •Group 3 - Untreated HIV controllers (not on ART for at least 8 weeks): HIV-1 RNA plasma level of < 2,000 copies/ml by standard assays, on 2 occasions, at least 1 week apart, and ART-naive.
- •Group 4 - ART treated with HIV-1 RNA plasma level of > 20 copies/ml by standard assays on 2 occasions, at least 1 week apart, while on combination antiretroviral therapy;
- •Groups 5A and 5B - ART treated with HIV-1 RNA plasma level of < 20 copies/ml by standard assays on 2 occasions, at least 1 week apart, while on combination antiretroviral therapy;
- •Current CD4 cell count > 300 cells/µl
- •If sexually active male and female, participating in sexual activity that could lead to pregnancy, agrees to use an effective method of contraception throughout the study.
排除标准
- •Group 1 (HIV-uninfected):
- •Confirmed HIV-1 or HIV-2 infection;
- •History of immunodeficiency or autoimmune disease; use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months;
- •Any clinically significant acute or chronic medical condition that in the opinion of the investigator would preclude participation;
- •Within the 12 months prior to enrollment, the volunteer has a history of sexually transmitted disease;
- •Hepatitis B (surface antigen, HbsAg) or hepatitis C (HCV antibodies);
- •Laboratory abnormalities in the parameters listed below:
- •Absolute neutrophil count ≤ 2,000
- •Hemoglobin ≤ 12 gm/dL if female; ≤ 13.5 gm/dL if male
- •Platelet count ≤ 140,000
- •ALT ≥ 1.25 x ULN
- •AST ≥ 1.25 x ULN
- •Total bilirubin ≥ 1.1 ULN
- •Creatinine ≥ 1.1 x ULN
- •Coagulation parameters (PT, PTT, INR) ≥ 1.1 x ULN
- •Pregnancy or breastfeeding;
- •Any vaccination within 14 days prior to 3BNC117 administration;
- •Receipt of any experimental HIV vaccine in the past or 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.
- •Groups 2-5 (HIV-infected):
- •History of AIDS-defining illness
- •History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months;
- •Any clinically significant acute or chronic medical condition, other than HIV infection, that in the opinion of the investigator would preclude participation;
- •Hepatitis B (surface antigen, HbsAg) or hepatitis C (HCV antibodies);
- •Laboratory abnormalities in the parameters listed below:
- •Absolute neutrophil count ≤ 1,300
- •Hemoglobin ≤ 10 gm/dL
- •Platelet count ≤ 125,000
- •ALT ≥ 2.0 x ULN
- •AST ≥ 2.0 x ULN
- •Total bilirubin ≥ 1.1 ULN
- •Creatinine ≥ 1.1 x ULN
- •Coagulation parameters ≥ 1.1 x ULN;
- •Current antiretroviral regimen includes either maraviroc or enfuvirtide;
- •Pregnancy or breastfeeding;
- •Any vaccination within 14 days prior to 3BNC117 administration;
- •Receipt of any experimental HIV vaccine or 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.
研究组 & 干预措施
Group 1A
HIV-uninfected individuals
1 mg/kg, single dose IV administration of 3BNC117
干预措施: 1 mg/kg, single dose IV administration of 3BNC117 (Biological)
Groups 1B
HIV-uninfected individuals 3 mg/kg, single dose IV administration of 3BNC117
干预措施: 3 mg/kg, single dose IV administration of 3BNC117 (Biological)
Group 1C
HIV-uninfected individuals 10 mg/kg, single dose IV administration of 3BNC117
干预措施: 10 mg/kg, single dose IV administration of 3BNC117 (Biological)
Group 1D
HIV-uninfected individuals 10 mg/kg, two doses IV of 3BNC117
干预措施: 10 mg/kg, two doses IV of 3BNC117 (Biological)
Group 1E
HIV-uninfected individuals 30 mg/kg, single dose IV administration of 3BNC117
干预措施: 30 mg/kg, single dose IV administration of 3BNC117 (Biological)
Group 1F
HIV-uninfected individuals 30 mg/kg, two doses IV of 3BNC117
干预措施: 30 mg/kg, two doses IV of 3BNC117 (Biological)
Group 2A
HIV-infected individuals on or off ART
1 mg/kg, single dose IV administration of 3BNC117
干预措施: 1 mg/kg, single dose IV administration of 3BNC117 (Biological)
Group 2B
HIV-infected individuals on or off ART 3 mg/kg, single dose IV administration of 3BNC117
干预措施: 3 mg/kg, single dose IV administration of 3BNC117 (Biological)
Group 2C
HIV-infected individuals on or off ART 10 mg/kg, single dose IV administration of 3BNC117
干预措施: 10 mg/kg, single dose IV administration of 3BNC117 (Biological)
Group 2D
HIV-infected individuals on or off ART 30 mg/kg, single dose IV administration of 3BNC117
干预措施: 30 mg/kg, single dose IV administration of 3BNC117 (Biological)
Group 2E
HIV-infected individuals off ART, VL 2,000-100,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
干预措施: 30 mg/kg, single dose IV administration of 3BNC117 (Biological)
Group 3
HIV-infected individuals off ART, VL < 2,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
干预措施: 30 mg/kg, single dose IV administration of 3BNC117 (Biological)
Group 4
HIV-infected individuals on ART, VL < 100,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
干预措施: 30 mg/kg, single dose IV administration of 3BNC117 (Biological)
Group 5A
HIV-infected individuals on ART, VL < 20 copies/ml 10 mg/kg, single dose IV administration of 3BNC117
干预措施: 10 mg/kg, single dose IV administration of 3BNC117 (Biological)
Group 5B
HIV-infected individuals on ART, VL < 20 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
干预措施: 30 mg/kg, single dose IV administration of 3BNC117 (Biological)
结局指标
主要结局
Safety and tolerability
时间窗: 24 weeks
To evaluate the safety and tolerability profile of one or two intravenous infusions of 3BNC117 at 3 increasing dose levels in HIV-infected and HIV-uninfected individuals.
次要结局
- Pharmacokinetic profile(24 hours post infusion)