Dual bNAb Treatment in Children

NCT ID: NCT03707977

Last Updated: 2025-05-14

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-17

Study Completion Date

2021-12-03

Brief Summary

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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

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 In Step 2, ART is withdrawn and dual bNAb maintenance treatment occurs.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

Conditions

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HIV Infection

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

ART

Intervention Type DRUG

ART will not be provided by the study. Participants will continue to receive their ART regimen they were receiving prior to enrolling in the study.

VRC01LS

Intervention Type BIOLOGICAL

Administered by intravenous (IV) infusion

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).

Group Type EXPERIMENTAL

ART

Intervention Type DRUG

ART will not be provided by the study. Participants will continue to receive their ART regimen they were receiving prior to enrolling in the study.

10-1074

Intervention Type BIOLOGICAL

Administered by intravenous (IV) infusion

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.

Group Type EXPERIMENTAL

ART

Intervention Type DRUG

ART will not be provided by the study. Participants will continue to receive their ART regimen they were receiving prior to enrolling in the study.

VRC01LS

Intervention Type BIOLOGICAL

Administered by intravenous (IV) infusion

10-1074

Intervention Type BIOLOGICAL

Administered by intravenous (IV) infusion

Interventions

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ART

ART will not be provided by the study. Participants will continue to receive their ART regimen they were receiving prior to enrolling in the study.

Intervention Type DRUG

VRC01LS

Administered by intravenous (IV) infusion

Intervention Type BIOLOGICAL

10-1074

Administered by intravenous (IV) infusion

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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.


* 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)

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)
Minimum Eligible Age

96 Weeks

Maximum Eligible Age

7 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Roger Shapiro, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Harvard School of Public Health (HSPH)

Daniel Kuritzkes, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Mathias Lichterfeld, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital/Massachusetts General Hospital

Locations

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Francistown Non-Network CRS

Francistown, , Botswana

Site Status

Botswana Harvard AIDS Institute Partnership CRS Non-Network

Gaborone, , Botswana

Site Status

Countries

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Botswana

References

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Capparelli EV, Ajibola G, Maswabi K, Holme MP, Bennett K, Powis KM, Moyo S, Mohammed T, Maphorisa C, Hughes MD, Seaton KE, Tomaras GD, Mosher S, Taylor A, O'Connell S, Narpala S, Mcdermott A, Caskey M, Gama L, Lockman S, Jean-Philippe P, Makhema J, Kuritzkes DR, Lichterfeld M, Shapiro RL; Tatelo Study Team. Safety and Pharmacokinetics of Intravenous 10-1074 and VRC01LS in Young Children. J Acquir Immune Defic Syndr. 2022 Oct 1;91(2):182-188. doi: 10.1097/QAI.0000000000003033.

Reference Type RESULT
PMID: 36094485 (View on PubMed)

Shapiro RL, Ajibola G, Maswabi K, Hughes M, Nelson BS, Niesar A, Pretorius Holme M, Powis KM, Sakoi M, Batlang O, Moyo S, Mohammed T, Maphorisa C, Bennett K, Hu Z, Giguel F, Reeves JD, Reeves MA, Gao C, Yu X, Ackerman ME, McDermott A, Cooper M, Caskey M, Gama L, Jean-Philippe P, Yin DE, Capparelli EV, Lockman S, Makhema J, Kuritzkes DR, Lichterfeld M. Broadly neutralizing antibody treatment maintained HIV suppression in children with favorable reservoir characteristics in Botswana. Sci Transl Med. 2023 Jul 5;15(703):eadh0004. doi: 10.1126/scitranslmed.adh0004. Epub 2023 Jul 5.

Reference Type RESULT
PMID: 37406137 (View on PubMed)

Banga J, Nelson BS, Ajibola G, Mohammed T, Maphorisa C, Boleo C, Moyo S, Batlang O, Sakoi-Mosetlhi M, Maswabi K, Holme MP, Powis KM, Lockman S, Hughes MD, Makhema J, Kuritzkes DR, Litcherfeld M, Shapiro R. Predictive markers for sustained viral suppression on dual bNAbs during ART interruption in children. J Acquir Immune Defic Syndr. 2025 Mar 26:10.1097/QAI.0000000000003663. doi: 10.1097/QAI.0000000000003663. Online ahead of print.

Reference Type RESULT
PMID: 40136003 (View on PubMed)

Sakoi-Mosetlhi M, Ajibola G, Haghighat R, Batlang O, Maswabi K, Pretorius-Holme M, Powis KM, Lockman S, Makhema J, Litcherfeld M, Kuritzkes DR, Shapiro R. Caregivers of children with HIV in Botswana prefer monthly IV Broadly Neutralizing Antibodies (bNAbs) to daily oral ART. PLoS One. 2024 Mar 27;19(3):e0299942. doi: 10.1371/journal.pone.0299942. eCollection 2024.

Reference Type RESULT
PMID: 38536810 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: PK Step

View Document

Document Type: Informed Consent Form: Steps 1 to 3

View Document

Other Identifiers

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38551

Identifier Type: REGISTRY

Identifier Source: secondary_id

Tatelo Study

Identifier Type: -

Identifier Source: org_study_id

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