Clinical trial NCT03707977: Dual bNAb Treatment in Children
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infection
Keywords: broadly neutralizing antibodies
HIV suppression
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2018-10-16
Enrollment: 30
Sex: ALL
Minimum age (years): 96
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 In Step 2, ART is withdrawn and dual bNAb maintenance treatment occurs.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

Eligibility 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)

Primary outcomes:
measure: Frequency of Treatment-associated Adverse Events (AEs) [Number of Participants With Treatment-associated Adverse Event(s) of Any Grade]
timeFrame: Measured until 30 days after study completion for each participant
measure: Severity of Treatment-associated AEs (Number of Participants With Grade 3 or Higher Related AEs)
timeFrame: Measured until 30 days after study completion for each participant
measure: Proportion of Children Who Maintain HIV-1 Plasma RNA Less Than 400 Copies/mL, After Initiating VRC01LS and 10-1074 Infusions and Stopping ART
timeFrame: Measured through Week 24 of Step 2
measure: Proportion of Children Who Maintain HIV-1 Plasma RNA Less Than 40 Copies/mL, After Initiating VRC01LS and 10-1074 Infusions and Stopping ART
timeFrame: Measured through Week 24 of Step 2
Secondary outcomes:
measure: VRC01LS or 10-1074 Concentrations in Plasma
timeFrame: Measured through Week 12 (PK Step)
measure: Median Trough Concentration of VRC01LS or 10-1074 in Plasma 28 Days After the Third Dose
timeFrame: Measured through Week 12 (PK Step)
measure: VRC01LS and 10-1074 Concentrations in Plasma for Each Time Point
timeFrame: Measured through Week 32 following Step 1 entry
measure: Proportion of Children With Trough VRC01LS and 10-1074 Concentrations Below Defined Trough Ranges
timeFrame: Measured through Week 32 following Step 1 entry
measure: Height Z-scores of Virally Suppressed Children Receiving bNAbs
timeFrame: Measured through Week 24 (Step 3)
measure: Weight Z-scores of Virally Suppressed Children Receiving bNAbs
timeFrame: Measured through Week 24 (Step 3)
Other outcomes:
Locations:
city: Francistown
country: Botswana
facility: Francistown Non-Network CRS
city: Gaborone
country: Botswana
facility: Botswana Harvard AIDS Institute Partnership CRS Non-Network
Study officials:
affiliation: Harvard School of Public Health (HSPH)
name: Roger Shapiro, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Daniel Kuritzkes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital/Massachusetts General Hospital
name: Mathias Lichterfeld, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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. doi: 10.1097/QAI.0000000000003663. Online ahead of print.
citation: 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.