Dual bNAb Treatment in Children

NCT03707977 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: Tatelo Study38551
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV Infection

Keywords

broadly neutralizing antibodies; HIV suppression

Outcome Measures

Primary Outcomes (4)

• 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

• 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.

  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

  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

  Measured through Week 24 of Step 2

Secondary Outcomes (6)

• VRC01LS or 10-1074 Concentrations in Plasma

  Measured through Week 12 (PK Step)

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

  Measured through Week 12 (PK Step)

• VRC01LS and 10-1074 Concentrations in Plasma for Each Time Point

  Measured through Week 32 following Step 1 entry

• Proportion of Children With Trough VRC01LS and 10-1074 Concentrations Below Defined Trough Ranges

  Measured through Week 32 following Step 1 entry

• Height Z-scores of Virally Suppressed Children Receiving bNAbs

  Measured through Week 24 (Step 3)

Study Arms (3)

Group PK-A: ART + VRC01LS

EXPERIMENTAL

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).

Drug: ART; Biological: VRC01LS

Group PK-B: ART + 10-1074

EXPERIMENTAL

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).

Drug: ART; Biological: 10-1074

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

EXPERIMENTAL

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.

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

Interventions

ART 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.

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

VRC01LS BIOLOGICAL

Administered by intravenous (IV) infusion

Group PK-A: ART + VRC01LS; Steps 1-3 Participants (ART + 10-1074 + VRC01LS)

10-1074 BIOLOGICAL

Administered by intravenous (IV) infusion

Group PK-B: ART + 10-1074; Steps 1-3 Participants (ART + 10-1074 + VRC01LS)

Eligibility Criteria

• Age: 96 Weeks - 7 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

Francistown Non-Network CRS

Francistown, Botswana

Location

Botswana Harvard AIDS Institute Partnership CRS Non-Network

Gaborone, Botswana

Location

Related Publications (6)

• 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.

  PMID: 36094485 RESULT

• 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.

  PMID: 37406137 RESULT

• 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.

  PMID: 40136003 RESULT

• 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.

  PMID: 38536810 RESULT

• Niesar A, Lancien M, Hong S, Naasz C, Ajibola G, Maswabi K, Sakoi-Mosetlhi M, Batlang O, Moyo S, Mohammed T, Maphorisa C, Carrere L, Roseto I, Hartana CA, Tan TS, Gao C, Parsons E, Hua R, Pretorius Holme M, Lockman S, Powis KM, Carrington M, Makhema J, Yu XG, Kuritzkes DR, Shapiro RL, Lichterfeld M. Immune correlates of HIV-1 rebound during broadly neutralizing antibody treatment in young children. J Clin Invest. 2026 Feb 16;136(4):e193912. doi: 10.1172/JCI193912. eCollection 2026 Feb 16.

  PMID: 41697750 RESULT

• Ajibola G, Nelson BS, Niesar A, Hong S, Lancien M, Holme MP, Hughes MD, Yin DE, Jean-Philippe P, Moyo S, Batlang O, Sakoi M, Maphorisa C, Mohammed T, Lockman S, Makhema J, Kuritzkes DR, Lichterfeld M, Shapiro RL. Long-Term Clinical, Immunologic, and Viral Reservoir Outcomes in Children Treated With VRC01LS and 10-1074 Monoclonal Antibodies in the Tatelo Study. Clin Infect Dis. 2026 Feb 25;82(2):e278-e285. doi: 10.1093/cid/ciaf568.

  PMID: 41078080 RESULT

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Molly Pretorius Holme
• Organization: Harvard T.H. Chan School of Public Health

mpretori@hsph.harvard.edu

617-432-4377

Study Officials

• Roger Shapiro, MD, MPH

  Harvard School of Public Health (HSPH)

  PRINCIPAL INVESTIGATOR

• Daniel Kuritzkes, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Mathias Lichterfeld, MD, PhD

  Brigham and Women's Hospital/Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: October 16, 2018
• Study Start: June 17, 2019
• Primary Completion: December 3, 2021
• Study Completion: December 3, 2021
• Last Updated: May 4, 2026
• Results First Posted: February 14, 2023

Record last verified: 2023-01

Locations

BO (2)