A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 10-1074 Monoclonal Antibody in HIV-infected and HIV-uninfected Individuals
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 3
- 主要终点
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
研究概览
简要总结
This is a phase 1 clinical trial to evaluate the safety, pharmacokinetics and the antiretroviral effects of the highly neutralizing anti-HIV-1 monoclonal antibody 10-1074 in HIV-infected and HIV-uninfected individuals.
详细描述
In preclinical studies carried out in humanized mice and non-human primates, 10-1074 alone or in combination with other neutralizing antibodies led to protection from HIV or simian/human immunodeficiency virus (SHIV) infection and also to sustained suppression of HIV plasma viremia. The aims of this protocol are to evaluate the safety, tolerability and pharmacokinetics profile of 10-1074 in both HIV-infected and HIV-uninfected individuals, and its antiretroviral activity in HIV-infected individuals.
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-infected)
- •Males and females, age 18 to 65
- •HIV-1 infection confirmed by two independent assays.
- •Group (1A-1C): HIV-infected individuals off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml by standard assays, or on ART with HIV-1 plasma RNA levels < 500 copies/ml. HIV-1 RNA levels should be measured on 2 occasions, at least 1 week apart and one measurement must be performed within 49 days prior to enrollment.
- •Group (1D): HIV-infected individuals off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml by standard assays, measured on 2 occasions, at least 1 week apart. At least one measurement must be performed within 49 days prior to enrollment.
- •Current CD4 count > 300 cells/μl.
- •If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception from 10 days prior to the 10-1074 infusion until the end of the study.
- •Group 2 (HIV-uninfected):
- •Males and females, age 18 to
- •Amenable to HIV risk reduction counseling and agrees to maintain behavior consistent with low risk of HIV exposure.
- •If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception throughout the study period, as described for the HIV-infected groups above.
排除标准
- •Group 1 (HIV-infected):
- •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.
- •Any clinically significant acute or chronic medical condition other than HIV infection, that in the opinion of the investigator would preclude participation.
- •Chronic Hepatitis B or Hepatitis C infection.
- •Laboratory abnormalities in the parameters listed below:
- •Absolute neutrophil count ≤ 1,000; Hemoglobin ≤10 gm/dL; Platelet count ≤100,000; ALT ≥ 2.0 x ULN; AST ≥ 2.0 x ULN; Total bilirubin ≥ 1.25 x ULN; Creatinine ≥ 1.1 x ULN; Coagulation parameters (PT, PTT or INR) ≥ 1.25 x ULN.
- •Pregnancy or lactation.
- •Any vaccination within 14 days prior to 10-1074 administration.
- •History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
- •Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
- •Group 2 (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 (such as autoimmune diseases) 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 infection.
- •Chronic Hepatitis B or Hepatitis C infection.
- •Laboratory abnormalities in the parameters listed:
- •Absolute neutrophil count ≤ 1,500; Hemoglobin ≤ 12 gm/dL if female; ≤ 13.5 gm/dL if male; Platelet count ≤ 140,000; Alanine transaminase (ALT) ≥ 1.25 x upper limit of normal (ULN); aspartate transaminase (AST) ≥ 1.25 x ULN; Total bilirubin ≥ 1.25 x ULN; Creatinine ≥ 1.1 x ULN; Coagulation parameters (prothrombin time - PT, partial thromboplastin time - PTT or INR) ≥ 1.25 x ULN.
- •Pregnancy or lactation.
- •Any vaccination within 14 days prior to 10-1074 administration.
- •Receipt of any experimental HIV vaccine in the past.
- •History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
- •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 2A
HIV-uninfected individuals
3 mg/kg, single dose IV administration of 10-1074
干预措施: 3 mg/kg, single dose IV administration of 10-1074 (Biological)
Group 1A
HIV-infected individuals Off ART, HIV-1 viral load < 100,000 copies/ml or On ART, HIV-1 viral load < 500 copies/ml
3 mg/kg, single dose IV administration of 10-1074
干预措施: 3 mg/kg, single dose IV administration of 10-1074 (Biological)
Group 1B
HIV-infected individuals Off ART, HIV-1 viral load < 100,000 copies/ml or On ART, HIV-1 viral load < 500 copies/ml
10 mg/kg, single dose IV administration of 10-1074
干预措施: 10 mg/kg, single dose IV administration of 10-1074 (Biological)
Group 1C
HIV-infected individuals Off ART, HIV-1 viral load < 100,000 copies/ml or On ART, HIV-1 viral load < 500 copies/ml
30 mg/kg, single dose IV administration of 10-1074
干预措施: 30 mg/kg, single dose IV administration of 10-1074 (Biological)
Group 1D
HIV-infected individuals Off ART, HIV-1 viral load < 100,000 copies/ml
30 mg/kg, single dose IV administration of 10-1074
干预措施: 30 mg/kg, single dose IV administration of 10-1074 (Biological)
Group 2B
HIV-uninfected individuals
10 mg/kg, single dose IV administration of 10-1074
干预措施: 10 mg/kg, single dose IV administration of 10-1074 (Biological)
Group 2C
HIV-uninfected individuals
30 mg/kg, single dose IV administration of 10-1074
干预措施: 30 mg/kg, single dose IV administration of 10-1074 (Biological)
Group 2D
HIV-uninfected individuals
30 mg/kg, single dose IV administration of 10-1074
干预措施: 30 mg/kg, single dose IV administration of 10-1074 (Biological)
结局指标
主要结局
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
时间窗: 24 weeks after 10-1074 administration
次要结局
- Serum peak concentration of 10-1074, measured in micrograms per ml(24 hours after 10-1074 administration)
- Serum half-life of 10-1074 expressed in days(24 Weeks after 10-1074 administration)
- Plasma HIV-1 RNA levels measured in copies/ml(2 weeks after 10-1074 administration)