A Clinical Trial to Evaluate the Impact of Broadly Neutralizing Antibodies VRC01LS and 10-1074 on Maintenance of HIV Suppression in a Cohort of Early-Treated Children in Botswana (Dual bNAb Treatment in Children)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Frequency of Treatment-associated Adverse Events (AEs) [Number of Participants With Treatment-associated Adverse Event(s) of Any Grade]
研究概览
简要总结
The purpose of this study is to evaluate the impact of two broadly neutralizing antibodies, VRC01LS and 10-1074, on the maintenance of HIV suppression in a cohort of early-treated children in Botswana.
详细描述
This study will evaluate the impact of two broadly neutralizing antibodies, VRC01LS and 10-1074, on the maintenance of HIV suppression in a cohort of early-treated children in Botswana.
The primary objectives are as follows:
- To conduct an interventional clinical trial to determine the safety, pharmacokinetics, dosing and antiviral efficacy of up to 24 weeks of maintenance VRC01LS and 10-1074 immunotherapy in early-treated HIV-1 infected children in Botswana.
- To evaluate effects of treatment with VRC01LS and 10-1074 on the size and cellular composition of residual viral reservoirs.
- To investigate the influence of VRC01LS and 10-1074 treatment on the magnitude and quality of antiviral innate and adaptive immune responses.
The study includes 4 steps: the pharmacokinetics (PK) Step, Step 1, Step 2, and Step 3. In the PK Step, antiretroviral treatment (ART) is continued and 12 study participants will undergo safety and PK testing, 6 for each bNAb used in the study (10-1074 and VRC01LS). In Step 1, ART is continued and dual bNAb treatment occurs, with PK confirmation of dual bNAb dosing for the first 6 participants in Step 1. In Step 2, ART is withdrawn and dual bNAb maintenance treatment occurs. In Step 3, dual bNAbs will be discontinued and participants will be re-started on ART.
Participants will be in the study for a minimum of 56 weeks, and a maximum of 98 weeks for those who start in the PK step and continue through the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 96 Weeks 至 7 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for PK Step*:
- •On ART for at least 96 weeks
- •Greater than or equal to 96 weeks and less than 5 years of age at enrollment
- •HIV RNA less than 40 copies/mL for at least 24 weeks prior to entry
- •Ability to remain in close study follow-up for at least 12 weeks
- •Willingness to receive IV infusions of bNAbs
- •Willingness to provide signed informed consent (by the parent/guardian)
- •*It is anticipated that all children in PK Step will be from Early Infant Treatment (EIT) Study (NCT02369406); however, up to 4 HIV+ children outside the PK Study (age range 2-5 years) may participate in the PK Step if otherwise eligible and if EIT children are unavailable.
- •Inclusion Criteria for Entry into Step 1 (followed by participation in Steps 2-3):
- •EIT Study participant (NCT02369406)
- •On ART for at least 96 weeks
- •Greater than or equal to 96 weeks and less than 7 years of age at enrollment
- •HIV RNA less than 40 copies/mL for at least 24 weeks prior to entry
- •Ability to remain in close study follow-up for at least 56 weeks
- •Willingness to receive IV infusions of bNAbs
- •Willingness to provide signed informed consent (by the parent/guardian)
排除标准
- •Medical condition making survival for at least 32 weeks unlikely
- •Active tuberculosis or malignancy
- •Actively breastfeeding
- •Previous receipt of VRC01/VRC01LS or 10-1074 (except during the PK Step)
研究组 & 干预措施
Steps 1-3 Participants (ART + 10-1074 + VRC01LS)
In Step 1, eligible participants will continue to receive ART and will receive both 10-1074 and VRC01LS at Weeks 0, 4, and 8. Following a recommendation from the study team and Safety Monitoring Committee (SMC) to increase the maintenance dosing based on the PK Step, a VRC01LS loading dose of 30 mg/kg will be given at the start of Step 1, followed by 15 mg/kg dosing at each 4-weekly visit, and 10-1074 dosing will be at 30 mg/kg at each 4-weekly visit. In Step 2, participants with ongoing viral suppression throughout Step 1 will undergo withdrawal of ART and will continue maintenance 10-1074 (30 mg/kg) and VRC01LS (15 mg/kg) treatment for up to 24 weeks. In Step 3, both 10-1074 and VRC01LS will be discontinued and ART will be re-started.
干预措施: 10-1074 (Biological)
Group PK-B: ART + 10-1074
In the PK Step, participants will continue ART and receive 10-1074 at Weeks 0, 4, and 8 as a single IV dose (30 mg/kg).
干预措施: ART (Drug)
Steps 1-3 Participants (ART + 10-1074 + VRC01LS)
In Step 1, eligible participants will continue to receive ART and will receive both 10-1074 and VRC01LS at Weeks 0, 4, and 8. Following a recommendation from the study team and Safety Monitoring Committee (SMC) to increase the maintenance dosing based on the PK Step, a VRC01LS loading dose of 30 mg/kg will be given at the start of Step 1, followed by 15 mg/kg dosing at each 4-weekly visit, and 10-1074 dosing will be at 30 mg/kg at each 4-weekly visit. In Step 2, participants with ongoing viral suppression throughout Step 1 will undergo withdrawal of ART and will continue maintenance 10-1074 (30 mg/kg) and VRC01LS (15 mg/kg) treatment for up to 24 weeks. In Step 3, both 10-1074 and VRC01LS will be discontinued and ART will be re-started.
干预措施: ART (Drug)
Group PK-A: ART + VRC01LS
In the PK Step, participants will continue ART and receive VRC01LS at Weeks 0, 4, and 8 as a single intravenous (IV) dose (30 mg/kg load then 10 mg/kg maintenance).
干预措施: VRC01LS (Biological)
Steps 1-3 Participants (ART + 10-1074 + VRC01LS)
In Step 1, eligible participants will continue to receive ART and will receive both 10-1074 and VRC01LS at Weeks 0, 4, and 8. Following a recommendation from the study team and Safety Monitoring Committee (SMC) to increase the maintenance dosing based on the PK Step, a VRC01LS loading dose of 30 mg/kg will be given at the start of Step 1, followed by 15 mg/kg dosing at each 4-weekly visit, and 10-1074 dosing will be at 30 mg/kg at each 4-weekly visit. In Step 2, participants with ongoing viral suppression throughout Step 1 will undergo withdrawal of ART and will continue maintenance 10-1074 (30 mg/kg) and VRC01LS (15 mg/kg) treatment for up to 24 weeks. In Step 3, both 10-1074 and VRC01LS will be discontinued and ART will be re-started.
干预措施: VRC01LS (Biological)
Group PK-A: ART + VRC01LS
In the PK Step, participants will continue ART and receive VRC01LS at Weeks 0, 4, and 8 as a single intravenous (IV) dose (30 mg/kg load then 10 mg/kg maintenance).
干预措施: ART (Drug)
Group PK-B: ART + 10-1074
In the PK Step, participants will continue ART and receive 10-1074 at Weeks 0, 4, and 8 as a single IV dose (30 mg/kg).
干预措施: 10-1074 (Biological)
结局指标
主要结局
Frequency of Treatment-associated Adverse Events (AEs) [Number of Participants With Treatment-associated Adverse Event(s) of Any Grade]
时间窗: Measured until 30 days after study completion for each participant
Severity of Treatment-associated AEs (Number of Participants With Grade 3 or Higher Related AEs)
时间窗: Measured until 30 days after study completion for each participant
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table). The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with Grade 1 indicating a mild event, Grade 2 indicating a moderate event, Grade 3 indicating a severe event, Grade 4 indicating a potentially life-threatening event, and Grade 5 indicating death.
Proportion of Children Who Maintain HIV-1 Plasma RNA Less Than 400 Copies/mL, After Initiating VRC01LS and 10-1074 Infusions and Stopping ART
时间窗: Measured through Week 24 of Step 2
Based on laboratory evaluations
Proportion of Children Who Maintain HIV-1 Plasma RNA Less Than 40 Copies/mL, After Initiating VRC01LS and 10-1074 Infusions and Stopping ART
时间窗: Measured through Week 24 of Step 2
Based on laboratory evaluations
次要结局
- VRC01LS or 10-1074 Concentrations in Plasma(Measured through Week 12 (PK Step))
- Median Trough Concentration of VRC01LS or 10-1074 in Plasma 28 Days After the Third Dose(Measured through Week 12 (PK Step))
- VRC01LS and 10-1074 Concentrations in Plasma for Each Time Point(Measured through Week 32 following Step 1 entry)
- Proportion of Children With Trough VRC01LS and 10-1074 Concentrations Below Defined Trough Ranges(Measured through Week 32 following Step 1 entry)
- Height Z-scores of Virally Suppressed Children Receiving bNAbs(Measured through Week 24 (Step 3))
- Weight Z-scores of Virally Suppressed Children Receiving bNAbs(Measured through Week 24 (Step 3))