Dual bNAb Treatment in Children

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 2; Phase 1

Conditions: HIV Infection

Treatments: Drug: ART; Biological: 10-1074; Biological: VRC01LS

Study type: Interventional

Funder types: NIH

Identifiers

NCT03707977

38551 (Registry Identifier)

Tatelo Study

Details and patient eligibility

About

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.

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 In Step 2, ART is withdrawn and dual bNAb maintenance treatment occurs.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

Enrollment: 30 patients

Sex: All

Ages: 96 weeks to 7 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria 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)

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Group PK-A: ART + VRC01LS

Experimental group

Description:

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).

Treatment:

Biological: VRC01LS

Drug: ART

Group PK-B: ART + 10-1074

Experimental group

Description:

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).

Treatment:

Biological: 10-1074

Drug: ART

Steps 1-3 Participants (ART + 10-1074 + VRC01LS)

Experimental group

Description:

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.

Treatment:

Biological: VRC01LS

Biological: 10-1074

Drug: ART