Safety and Immunogenicity of Stabilized CH505 TF chTrimer Vaccination in Adults Living With HIV-1 on Suppressive Antiretroviral Therapy
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 30
- 试验地点
- 24
- 主要终点
- Proportion of participants who initiated active study treatment (CH505 TF chTrimer, 3M-052-AF and Alum) who met the study-defined primary safety composite endpoint
研究概览
简要总结
A5422 is a phase 1, randomized, double-blind, placebo-controlled clinical trial to assess the safety, tolerability, and immunogenicity of a vaccination with stabilized CH505 TF chTrimer admixed with 3M-052-AF + Aluminum hydroxide (Alum), to assess the effect of CH505 TF chTrimer vaccine as a therapeutic vaccine in adults living with HIV-1 on suppressive antiretroviral therapy (ART) with the aim of inducing new HIV-1 Envelope (Env) B-cell neutralizing immune responses. Participants will be on study for up to 100 weeks (52 weeks on study treatment plus 48 weeks follow-up).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Randomized (2:1), 20 participants in Arm 1 and 10 participants in Arm 2
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-1 infection
- •On a suppressive ART regimen for at least 24 months with no changes in the 90 days prior to study entry
- •CD4+ cell count greater than 200 cells/mm3 obtained within 56 days prior to study entry
- •HIV-1 RNA <200 copies/mL obtained within 56 days prior to study entry
- •Plasma HIV-1 RNA levels <200 copies/mL for at least 12 months on ART prior to study entry
- •The following laboratory values obtained within 56 days prior to study entry
- •White blood cell count ≥2,500 cells/mm3
- •Absolute neutrophil count (ANC) >750/mm3
- •Hemoglobin ≥11 g/dL for cisgender men/transgender women and ≥10 g/dL for cisgender women/transgender men
- •Platelet count ≥100,000/mm3
- •Creatinine <1.5x upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) (SGPT) ≤1.5 ULN
- •Hepatitis C Virus (HCV) antibody-negative or HCV RNA negative result if indicated, within 56 days prior to study entry
- •Negative hepatitis B surface antigen (HBsAg) result obtained within 56 days prior to study entry
- •For study candidates of child-bearing potential, negative serum or urine pregnancy test at screening and within 48 hours prior to study entry
- •No participation in conception process and agree to use at least one reliable form of contraception if participating in sexual activity that could lead to pregnancy during the study and for 8 weeks following the final study vaccine
排除标准
- •Known to have started ART during acute HIV infection
- •Known to have HIV-related opportunistic infections within the last 2 years prior to study entry.
- •History of malignancy within the last 5 years prior to study entry.
- •Currently breastfeeding
- •History of or active autoimmune disorders
- •HIV vaccination (prophylactic and/or therapeutic) within 1 year prior to study entry
- •Receipt of any anti-HIV-1 bNAbs within 2 years prior to study entry
- •Vaccination within 4 weeks prior to study entry
- •Use of any infusion blood product or immune globulin within 16 weeks prior to study entry (Exception: COVID-19-specific monoclonal antibodies are allowed)
- •Use of systemic immunomodulators, systemic cytotoxic chemotherapy, or non-FDA approved investigational therapy within 60 days prior to study entry
- •Intent to use immunomodulators during the course of the study
- •Immune deficiency other than HIV
- •HCV antiviral therapy within 90 days prior to screening
- •Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation
- •Active drug or alcohol use or dependence that would interfere with adherence to study requirements
- •Acute or serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry
- •Conditions that would preclude injection site reaction assessments (e.g., extensive tattoos, scarring, skin conditions).
研究组 & 干预措施
Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg)
干预措施: CH505 TF chTrimer (Biological)
Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg)
干预措施: 3M-052-AF (Biological)
Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg)
干预措施: Aluminum Hydroxide Suspension (Biological)
Study Arm 2: Placebo (sodium chloride for injection, 0.9% USP)
干预措施: Sodium Chloride for Injection (Other)
结局指标
主要结局
Proportion of participants who initiated active study treatment (CH505 TF chTrimer, 3M-052-AF and Alum) who met the study-defined primary safety composite endpoint
时间窗: Day 0 (after initial vaccination) to 4 weeks (28 days) after the last vaccination
The study-defined primary safety endpoint is a composite endpoint. A participant who has initiated active study treatment is considered to have met the endpoint if the participant has experienced any treatment-related (i.e., related to CH505 TF chTrimer, 3M-052-AF or Alum as judged by the core team, blinded to study treatment) 1) serious adverse event (SAE), or 2) Grade 3+ adverse event (AE), or 3) AE that led to permanent discontinuation of study treatment regardless of grade
Number of the viruses with antibody neutralization response for a cross-clade global panel of 9 viruses expressing heterologous envelopes determined using a neutralization assay
时间窗: Day 0 pre-vaccination to 2 weeks (14 days) after the fifth vaccination
次要结局
- Antibody neutralization response for vaccine-matched and related viruses(Day 0 pre-vaccination to 2 weeks (14 days) after the fifth vaccination)