A Phase 1 Study to Evaluate the Safety, Immunologic and Virologic Responses of MGD014 Therapy in HIV-Infected Individuals on Suppressive Antiretroviral Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- MacroGenics
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Number of Participants With Treatment-Emerging Adverse Events
研究概览
简要总结
This is a Phase 1, open-label single-center study to determine the safety of MGD014 in participants with human immunodeficiency virus (HIV) infection on stable suppressive antiretroviral therapy (ART).
详细描述
Eligible participants will be maintained on ART and receive either one infusion (Part 1) or multiple infusions of MGD014 (Part 2). Part 1 is a single ascending dose study with a 1+3 design for the first 2 dose cohorts, and a 3+3 design with staggered accrual for the 6 higher dose cohorts, with an aim of determining the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ascending doses up to either the Optimal Biologic Dose (OBD) or the maximum administered dose (MAD).
Part 2 is a multi-dose expansion cohort with MGD014 administered at the OBD, as determined in Part 1. In Part 2, additional assessments on the effects of MGD014 on HIV latent infection parameters will be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Ability and willingness of participant to provide written informed consent.
- •HIV-1 infection, documented by any FDA-approved rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
- •On a potent, stable, continuous ART regimen for ≥ 24 months prior to Screening.
- •Plasma HIV-1 RNA < 50 copies/mL at two time points in the previous 12 months prior to screening (one time point can be screening) and never ≥ 50 copies/mL on 2 consecutive time points in the last 24 months.
- •Adequate organ function based on acceptable laboratory parameters.
排除标准
- •Women of childbearing potential defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or menopause.
- •History or other evidence of severe illness, immunodeficiency other than HIV, or any other condition that would make the potential participant unsuitable for study.
- •History or other evidence of any condition or process for which signs or symptoms could be confused with reactions to MGD
- •History of any HIV immunotherapy or HIV vaccine except for MGD014 within 12 months prior to screening.
- •History of clinically significant cardiovascular disease, severe allergic reactions, malignancy (except non-melanoma skin cancer) within 5 years, seizure disorder within 2 years, organ/tissue transplant, autoimmune disease, unstable asthma, bleeding disorder.
- •Evidence of active viral, or antifungal treatment within 7 days prior to the initiation of study drug
- •Active, asymptomatic, or suspected COVID-19/SARS-CoV-2 infection.
- •Active, untreated syphilis.
- •Use of blood products, cytokine therapy, growth-stimulating factors, cytotoxic chemotherapy or investigational therapy within 90 days.
- •Current use of the antivirals maraviroc and/or enfuvirtide.
- •Any vaccination with exception of flu vaccine within 30 days of screening.
结局指标
主要结局
Number of Participants With Treatment-Emerging Adverse Events
时间窗: up to 77 days
Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.
次要结局
- AUC Inf: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity of MGD014(Study Day 0 to 42)
- Cmax: Maximum Plasma Concentration(Study Day 0)
- Clearance(Study Day 0 to 42)
- Vz: Terminal Phase Volume of Distribution of MGD014(Study Day 1, 2, 7, 14, 21, 28, and 42 (single infusion) and Study Day 1, 3, 14, 28, 42, and 77 (multiple infusions))
- Number of Participants With Increased Cytokine Levels(Study Day 1, 2 and 7 (single infusion) and Study Day 1, 3, 14 and 28 (multiple infusions))
- Ctrough: Trough Level Concentration(Study Day 14)
- Terminal Half Life of MGD014(Study Day 0 to Study Day 42)
- Tmax: Time to Maximum Concentration(Study Day 0)
- Number of Participants That Developed Antidrug Antibodies to MGD014(Study Day 1, 14, 28 and 42 (single infusion) and Study Day 1, 14, 28 and 77 (multiple infusions))