A Phase 1 Randomized Placebo-controlled Clinical Trial of the Safety, Pharmacokinetics and Antiviral Activity of PGT121 Monoclonal Antibody (mAb) in HIV-uninfected and HIV-infected Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Pharmacokinetics: elimination half-life (t1/2)
研究概览
简要总结
This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGT121 monoclonal antibody for HIV prevention and therapy.
详细描述
This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGT121 monoclonal antibody for HIV prevention and therapy. PGT121 mAb is a recombinant human IgG1 monoclonal antibody that targets a V3 glycan-dependent epitope region of the HIV envelope protein. PGT121 mAb was chosen for this study because it is potent, neutralizes a wide array of HIV viruses, and can prevent and treat simian-human immunodeficiency virus (SHIV) in rhesus monkeys.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
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
- •HIV-uninfected males or females age 18-50 years old
- •Willing to maintain low risk behavior for HIV infection
排除标准
- •confirmed HIV-infection, pregnancy or lactation, significant acute or chronic disease and clinically significant laboratory abnormalities
- •Group 2 Inclusion Criteria:
- •HIV-infected males or females age 18-65 years old
- •On a stable antiretroviral regimen with HIV-1 RNA plasma level <50 copies/ml, CD4 cell count greater than or equal to 300 cells/uL
- •Group 2 Exclusion Criteria:
- •history of AIDS-defining illness within the previous 5 years, significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities
- •Group 3 Inclusion Criteria:
- •HIV-infected males or females age 18-65
- •Not on antiretroviral therapy for > 6 months with detectable HIV-1 viral load between 100 and 100,000 copies/ml, CD4 cell count greater than or equal to 300 cells/uL
- •Group 3 Exclusion Criteria:
- •history of AIDS-defining illness within the previous 5 years, significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities
研究组 & 干预措施
Group 1C
HIV-uninfected participants
干预措施: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 1C
HIV-uninfected participants
干预措施: PGT121 30mg/kg IV (Biological)
Group 2A
HIV-infected on ART, (<50 cp/ml)
干预措施: PGT121 3mg/kg IV (Biological)
Group 1A
HIV-uninfected participants
干预措施: PGT121 3mg/kg IV (Biological)
Group 1A
HIV-uninfected participants
干预措施: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 1B
HIV-uninfected participants
干预措施: PGT121 10mg/kg IV (Biological)
Group 1B
HIV-uninfected participants
干预措施: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 2A
HIV-infected on ART, (<50 cp/ml)
干预措施: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 2B
HIV-infected on ART, (<50 cp/ml)
干预措施: PGT121 10mg/kg IV (Biological)
Group 2B
HIV-infected on ART, (<50 cp/ml)
干预措施: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 2C
HIV-infected on ART, (<50 cp/ml)
干预措施: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 2C
HIV-infected on ART, (<50 cp/ml)
干预措施: PGT121 30mg/kg IV (Biological)
Group 3A
HIV-Infected off ART (VL 2x10^3 - 1x10^5 cp/ml)
干预措施: PGT121 30mg/kg IV (Biological)
Group 3B
HIV-Infected off ART (VL 1x10^2 - 2x10^3 cp/ml)
干预措施: PGT121 30mg/kg IV (Biological)
Arm 1D
HIV-uninfected participants
干预措施: PGT121 3mg/kg SC (Biological)
Arm 1D
HIV-uninfected participants
干预措施: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
结局指标
主要结局
Pharmacokinetics: elimination half-life (t1/2)
时间窗: 6 Months post infusion
Pharmacokinetics: elimination half-life (t1/2)
Pharmacokinetics: Clearance (CL/F)
时间窗: 6 Months post infusion
Pharmacokinetics: Clearance (CL/F)
Pharmacokinetics: Volume of distribution (Vz/F)
时间窗: 6 months post infusion
Pharmacokinetics: Volume of distribution (Vz/F)
Pharmacokinetics: Area under the concentration decay curve (AUC)
时间窗: 6 months post infusion
Pharmacokinetics: Area under the concentration decay curve (AUC)
Proportion of participants with PGT121 mAb reactogenicity, related AEs and SAEs
时间窗: 6 Months post infusion
The investigators will measure the following endpoints to evaluate the safety and tolerability of PGT121 mAb in HIV-uninfected and HIV-infected adults: 1. Proportion of participants with moderate or greater reactogenicity (e.g., solicited adverse events) for 3 days following IV infusion of PGT121 mAb. 2. Proportion of participants with moderate or greater and/or PGT121 mAb-related unsolicited adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, following IV infusion of PGT121 mAb for the first 56 days post administration of Investigational Product. 3. Proportion of participants with PGT121 mAb-related serious adverse events (SAEs) throughout the study period.
Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure
时间窗: 6 months post infusion
Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure
Antiviral Activity
时间窗: 6 Months post infusion
Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values)
次要结局
未报告次要终点