Dual bNAb Treatment in Children

National Institute of Allergy and Infectious Diseases (NIAID)30 enrolled

Overview

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.

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 In Step 2, ART is withdrawn and dual bNAb maintenance treatment occurs.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

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV Infection

Interventions

ARTDRUG

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.

VRC01LSBIOLOGICAL

Administered by intravenous (IV) infusion

10-1074BIOLOGICAL

Administered by intravenous (IV) infusion

Eligibility

Sex: ALLMin age: 96 WeeksMax age: 7 Years

Medical Language ↔ Plain English

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)

Locations (2)

Francistown Non-Network CRS

Francistown, Botswana

Botswana Harvard AIDS Institute Partnership CRS Non-Network

Gaborone, Botswana

Outcomes

Primary Outcomes

Frequency of Treatment-associated Adverse Events (AEs) [Number of Participants With Treatment-associated Adverse Event(s) of Any Grade]

Time frame: 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)

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.

Time frame: Measured until 30 days after study completion for each participant

Proportion of Children Who Maintain HIV-1 Plasma RNA Less Than 400 Copies/mL, After Initiating VRC01LS and 10-1074 Infusions and Stopping ART

Based on laboratory evaluations

Time frame: Measured through Week 24 of Step 2

Proportion of Children Who Maintain HIV-1 Plasma RNA Less Than 40 Copies/mL, After Initiating VRC01LS and 10-1074 Infusions and Stopping ART

Based on laboratory evaluations

Time frame: Measured through Week 24 of Step 2

Secondary Outcomes

VRC01LS or 10-1074 Concentrations in Plasma

Median pre-dose trough (28 days post previous dose) based on laboratory evaluations

Time frame: Measured through Week 12 (PK Step)

Median Trough Concentration of VRC01LS or 10-1074 in Plasma 28 Days After the Third Dose

Based on laboratory evaluations

Time frame: Measured through Week 12 (PK Step)

Data from ClinicalTrials.gov

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