Dual bNAb Treatment in Children

Phase 1

Completed

• Conditions: HIV Infection
• Interventions: Drug: ART; Biological: VRC01LS; Biological: 10-1074

• Registration Number: NCT03707977
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

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.

Detailed Description

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:

1. 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.

2. To evaluate effects of treatment with VRC01LS and 10-1074 on the size and cellular composition of residual viral reservoirs.

3. 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 In Step 2, ART is withdrawn and dual bNAb maintenance treatment occurs.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.

Study Timeline

• Study First Submitted: 2018-10-12
• Study First Submitted QC: 2018-10-12
• Study First Posted: 2018-10-16
• Study Start: 2019-06-17
• Primary Completion: 2021-12-03
• Study Completion: 2021-12-03
• Results First Submitted: 2022-12-02
• Status Verified: 2023-01
• Results First Submitted QC: 2023-01-18
• Results First Posted: 2023-02-14
• Last Update Submitted: 2024-09-30
• Last Update Posted: 2024-10-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

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Exclusion Criteria

• 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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Steps 1-3 Participants (ART + 10-1074 + VRC01LS)	10-1074	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.
Group PK-B: ART + 10-1074	ART	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).
Steps 1-3 Participants (ART + 10-1074 + VRC01LS)	ART	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.
Group PK-A: ART + VRC01LS	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).
Steps 1-3 Participants (ART + 10-1074 + VRC01LS)	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.
Group PK-A: ART + VRC01LS	ART	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).
Group PK-B: ART + 10-1074	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).

Primary Outcome Measures

Name	Time	Method
Severity of Treatment-associated AEs (Number of Participants With Grade 3 or Higher Related AEs)	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	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	Measured through Week 24 of Step 2	Based on laboratory evaluations
Frequency of Treatment-associated Adverse Events (AEs) [Number of Participants With Treatment-associated Adverse Event(s) of Any Grade]	Measured until 30 days after study completion for each participant

Secondary Outcome Measures

Name	Time	Method
VRC01LS or 10-1074 Concentrations in Plasma	Measured through Week 12 (PK Step)	Median pre-dose trough (28 days post previous dose) based on laboratory evaluations
Median Trough Concentration of VRC01LS or 10-1074 in Plasma 28 Days After the Third Dose	Measured through Week 12 (PK Step)	Based on laboratory evaluations
VRC01LS and 10-1074 Concentrations in Plasma for Each Time Point	Measured through Week 32 following Step 1 entry	Based on laboratory evaluations
Proportion of Children With Trough VRC01LS and 10-1074 Concentrations Below Defined Trough Ranges	Measured through Week 32 following Step 1 entry	Based on laboratory evaluations
Height Z-scores of Virally Suppressed Children Receiving bNAbs	Measured through Week 24 (Step 3)	World Health Organization (WHO) standardized Z-scores will be evaluated for changes over time: WHO Length/height-for-age z-score (0-19 yrs), Change from Step 1, Day 0 to Step 3, Week 24. A z-score of 0 corresponds to the population mean. Scores above 0 indicate a participant's height is above the mean, while a score below 0 indicates a participant's height is below the mean. A positive change in z-score corresponds to a higher z-score at the second timepoint compared to the first.
Weight Z-scores of Virally Suppressed Children Receiving bNAbs	Measured through Week 24 (Step 3)	WHO standardized Z-scores will be evaluated for changes over time: WHO Weight-for-age z-score (0-10 yrs), Change from Step 1, Day 0 to Step 3, Week 24. A z-score of 0 corresponds to the population mean. Scores above 0 indicate a participant's weight is above the mean, while a score below 0 indicates a participant's weight is below the mean. A positive change in z-score corresponds to a higher z-score at the second timepoint compared to the first.

Trial Locations

Locations (2)

Francistown Non-Network CRS; 🇧🇼 Francistown, Botswana

Botswana Harvard AIDS Institute Partnership CRS Non-Network; 🇧🇼 Gaborone, Botswana