A clinical trial to evaluate the impact of broadly neutralizing antibody VRC01 on HIV viral reservoir and maintenance of suppression in a cohort of early-treated children in Botswana

一项临床试验，旨在评估广泛中和抗体 VRC01 对博茨瓦纳早期治疗儿童队列中 HIV 病毒库的影响以及维持抑制

• 批准号: 10700262
• 负责人: Daniel R. Kuritzkes
• 金额: $ 99.37万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-20 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700262
• 关键词: Adult; Aftercare; Anti-Retroviral Agents; Antibody Therapy; Archives; Autologous; Binding; Biological Assay; Birth; Blood specimen; Botswana; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; COVID-19; Cells; Characteristics; Child; Chromosomes; Clinical; Clinical Data; Clinical Markers; Clinical Research; Clinical Trials; Complex; Coupled; DNA; Data; Dose; Drug Kinetics; Enrollment; Evaluation; Evolution; Failure; Frequencies; Gene Expression; Growth; HIV; HIV Genome; HIV-1; Homeostasis; Hour; Immune; Immune response; Immune system; Immunologic Markers; Immunologics; Immunotherapy; Infant; Infection; Innate Immune Response; Interruption; Intervention; Intervention Studies; Kinetics; Length; Life; Longterm Follow-up; Maintenance; Measurement; Monitor; Monoclonal Antibody Therapy; Multi-Institutional Clinical Trial; Outcome; Participant; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Phase; Phenotype; Plasma; Population; RNA; Research Infrastructure; Residual state; Safety; Serious Adverse Event; Severities; Site; T-Lymphocyte; Testing; Time; Variant; Viral; Viral reservoir; Virus; Withdrawal; adaptive immune response; anti-viral efficacy; antiviral drug development; cohort; design; efficacy evaluation; exhaustion; experience; follow-up; immune activation; intrapartum; neutralizing antibody; neutralizing monoclonal antibodies; novel; open label; pediatric patients; primary endpoint; recruit; research clinical testing; secondary endpoint; small molecule; success; timeline; transcriptome sequencing; treatment effect; viral rebound

The Dual bNAb Treatment in Children Study (“Tatelo”) is an ongoing phase I/II, multi-site clinical trial of dual treatment with two broadly neutralizing monoclonal antibodies (bNAbs), VRC01LS and 10-1074, offered to HIV-1 infected virally suppressed children. The study is evaluating the efficacy of dual bNAbs for maintaining viral suppression in the absence of ART among virally suppressed HIV-infected children who started standard ART within 96 hours of birth (or soon after intrapartum infection). All children in the Tatelo Study were recruited from the Early Infant Treatment (EIT) study (U01AI114235), and have been followed from birth with frequent assessments of their clinical, virologic and immunologic characteristics. Children who received at least 96 weeks of ART and met virologic entry criteria were offered enrollment into the Tatelo Study. The intervention consisted of two PK and safety phases (single and then dual bNAbs), followed by the main study intervention (dual bNAbs plus ART for at least 8 weeks, then dual bNAbs alone for up to 24 weeks), and then a follow-up period when children were returned to ART alone. The study is designed to evaluate three possible benefits of dual bNAb therapy in HIV-1-infected children: 1) to determine the duration of virologic control that can be maintained with dual bNAb treatment following early ART, providing proof-of-concept that bNAbs may serve as a possible alternative to standard ART in children with low viral reservoirs; 2) to investigate whether bNAb therapy is associated with changes in the size and/or the cellular or clonal composition of residual viral reservoirs, which will be highly informative for developing strategies to limit viral persistence and to destabilize viral reservoir homeostasis in pediatric patients; and 3) to evaluate whether treatment with bNAbs is associated with qualitative or quantitative changes in innate or adaptive antiviral immune responses, and if it facilitates the development of an antiviral immune profile that can enable spontaneous post-treatment viral control.

儿童双重bNAb治疗研究（"Tatelo"）是一项正在进行的双重bNAb治疗的I/II期、多中心临床试验。 用两种广泛中和的单克隆抗体（bNAb），VRC01LS和10 - 1074， HIV-1感染的病毒抑制儿童。该研究正在评估双重bNAb用于维持 在没有ART的情况下，开始标准治疗的病毒抑制HIV感染儿童中的病毒抑制 出生后96小时内（或分娩时感染后不久）接受抗逆转录病毒治疗。 Tatelo研究中的所有儿童均来自早期婴儿治疗（EIT）研究（U01AI114235）， 并从出生起就经常对其进行临床、病毒学和免疫学评估， 特色接受至少96周抗逆转录病毒治疗并符合病毒学入选标准的儿童 入组Tatelo研究。干预包括两个PK和安全性阶段（单次，然后 双重bNAb），然后是主要研究干预（双重bNAb + ART至少8周，然后是双重bNAb + ART至少8周， bNAbs单独治疗长达24周），然后是一个随访期，儿童仅返回ART治疗。 该研究旨在评估双重bNAb治疗HIV-1感染儿童的三种可能益处： 1)为了确定在以下情况下双重bNAb治疗可以维持的病毒学控制的持续时间， 早期ART，提供概念验证，bNAb可作为标准ART的可能替代品， 低病毒库的儿童; 2）研究bNAb治疗是否与 残留病毒库的大小和/或细胞或克隆组成，这将是高度信息化的 制定策略以限制病毒持续存在并破坏儿科中病毒库的稳态 3）评估bNAb治疗是否与定性或定量 先天性或适应性抗病毒免疫反应的变化，如果它促进了 抗病毒免疫谱，可以使自发的治疗后病毒控制。