A Phase 1 Randomized Placebo-controlled Clinical Trial of the Safety, Pharmacokinetics and Antiviral Activity of PGDM1400 and PGT121 and VRC07-523LS Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Safety and tolerability
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 PGDM1400 and PGT121 and VRC07-523LS mAbs 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 PGDM1400, PGT121 and VRC07-523LS mAbs for HIV prevention and therapy. PGDM1400, PGT121 and VRC07-523LS mAbs are recombinant human IgG1 monoclonal antibodies that target V1V2 (PGDM1400), a V3 glycan-dependent epitope (PGT121) and the CD4 binding site (VRC07-523LS) epitope region of the HIV envelope protein. PGT121, PGDM1400 and VRC07-523LS mAb were chosen for this study because of their potency, their ability to neutralize a wide array of cross-clade HIV viruses in a complementary pattern and their proven antiviral activity in animal studies e.g., their capacity to robustly 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
- •Groups 1 and 2 Inclusion Criteria:
- •HIV-uninfected males or females age 18-50 years old
- •Willing to maintain low risk behavior for HIV infection
- •Groups 1 and 2
排除标准
- •Confirmed HIV-infection, pregnancy or lactation, significant acute or chronic disease and clinically significant laboratory abnormalities
- •Group 3 Inclusion Criteria:
- •HIV-infected males or females age 18-65 years old
- •Not on antiretroviral therapy with HIV-1 RNA plasma level between 1,000 and 100,000 copies/ml, CD4 cell count ≥ 300 cells/uL
- •Group 3 Exclusion Criteria:
- •Significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities
研究组 & 干预措施
Group 1A HIV-Uninfected
PGDM1400 low dose
干预措施: PGDM1400/Placebo (3mg/kg IV) (Biological)
Group 1B HIV-Uninfected
PGDM1400 mid dose
干预措施: PGDM1400/Placebo (10mg/kg IV) (Biological)
Group 1C HIV-Uninfected
PGDM1400 high dose
干预措施: PGDM1400/Placebo (30mg/kg IV) (Biological)
Group 2A HIV-Uninfected
PGDM1400 + PGT121 low dose
干预措施: PGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV) (Biological)
Group 2B HIV-Uninfected
PGDM1400 + PGT121 mid dose
干预措施: PGDM1400 + PGT121/Placebo (10mg/kg + 10mg/kg IV) (Biological)
Group 2C HIV-Uninfected
PGDM1400 + PGT121 high dose
干预措施: PGDM1400 + PGT121/Placebo (30mg/kg + 30mg/kg IV) (Biological)
Group 3A HIV-infected off ART
PGDM1400 + PGT121 + VRC07-523LS at 20mg/kg; HIV+ without ART
干预措施: PGDM1400 + PGT121 + VRC07-523LS (20mg/kg + 20mg/kg + 20 mg/kg IV) (Biological)
Group 3B HIV-infected off ART
PGDM1400 + PGT121 at high dose; HIV + without ART
干预措施: PGDM1400 + PGT121 (MTD IV) (Biological)
结局指标
主要结局
Safety and tolerability
时间窗: 6 Months post infusion
1. Proportion of participants with moderate or greater reactogenicity (e.g., solicited adverse events) for 3 days following IV infusion of PGDM1400 mAb alone, and a combination of PGDM1400 mAb and PGT121 mAb, and a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb 2. Proportion of participants with adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, during the first 56 days following IV infusion of PGDM1400 mAb alone and a combination of PGDM1400 mAb and PGT121 mAb, and a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb, that are moderate or greater, and/or related to PGDM1400 mAb or PGT121 mAb or VRC07-523LS mAb 3. Proportion of participants with SAEs throughout the study period following IV infusion of PGDM1400 mAb alone and a combination of PGDM1400 mAb and PGT121 mAb, and a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb, that are related to PGDM1400 mAb or PGT121 mAb or VRC07-523LS mAb
Elimination half-life (t1/2)
时间窗: 6 Months post infusion
Elimination half-life following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults
Clearance (CL/F)
时间窗: 6 months post infusion
Clearance following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults.
Volume of distribution (Vz/F)
时间窗: 6 months post infusion
Volume of distribution following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults
Area under the concentration decay curve (AUC)
时间窗: 6 months post infusion
AUC following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults
Impact of viral load and/or ART
时间窗: 6 months post infusion
Impact of viral load and/or ART on PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb disposition
Antiviral activity of PGDM1400 in combination with PGT121 or PGDM1400 in combination with PGT121 and VRC07-523LS mAbs
时间窗: 6 Months post infusion
Antiviral activity following IV infusion of PGDM1400 mAb in combination with PGT121 mAb, or PGDM1400 mAb in combination with PGT121 mAb and VRC07-523LS mAb, in viremic HIV-infected adults not on ART: Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values)
次要结局
- Serum antibody titers against bNAbs(6 Months post infusion)
- CD4+ T cell count(6 Months post infusion)
- HIV genotyping of circulating virus(6 Months post infusion)
- HIV phenotyping of circulating virus(6 months post infusion)