HIV InfectionPhase 1/2NCT03707977
Dual bNAb Treatment in Children
A Phase 1/2 study testing ART, VRC01LS and 10-1074 in people with HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in Botswana.
Trial 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. Read more about this study
- Who is it for?
- Ages 96 weeks to 7 years
- Conditions the study is for
- HIV Infection
- What is being tested?
- ART, VRC01LS and 10-1074
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesBotswana
- Study dates
- 17 Jun 2019to 3 Dec 2021
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 96 weeks to 7 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
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- *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)
Who cannot join
- 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 locations and contacts
2 sites in 1 country.
Botswana2 sites
Francistown Non-Network CRS
Francistown
Botswana Harvard AIDS Institute Partnership CRS Non-Network
Gaborone
About this study
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)
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.
Read the 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:
- 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.
- To evaluate effects of treatment with VRC01LS and 10-1074 on the size and cellular composition of residual viral reservoirs.
- 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
- HIV Infection
- Being tested
- ART, VRC01LS, 10-1074
- Keywords
- broadly neutralizing antibodies, HIV suppression
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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. Receives: Drug: ART; Biological: VRC01LS; Biological: 10-1074 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Treatment-associated Adverse Events (AEs) [Number of Participants With Treatment-associated Adverse Event(s) of Any Grade]
Measured: 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: 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: 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: Measured through Week 24 of Step 2
Secondary outcomes (6)
VRC01LS or 10-1074 Concentrations in Plasma
Median pre-dose trough (28 days post previous dose) based on laboratory evaluations
Measured: 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
Measured: Measured through Week 12 (PK Step)
VRC01LS and 10-1074 Concentrations in Plasma for Each Time Point
Based on laboratory evaluations
Measured: Measured through Week 32 following Step 1 entry
Proportion of Children With Trough VRC01LS and 10-1074 Concentrations Below Defined Trough Ranges
Based on laboratory evaluations
Measured: Measured through Week 32 following Step 1 entry
Height Z-scores of Virally Suppressed Children Receiving bNAbs
World Health Organization (WHO) standardized Z-scores will be evaluated for changes over time: WHO Length/height-for-age z-score (0-19 yrs), Change from Step 1, Day 0 to Step 3, Week 24. A z-score of 0 corresponds to the population mean. Scores above 0 indicate a participant's height is above the mean, while a score below 0 indicates a participant's height is below the mean. A positive change in z-score corresponds to a higher z-score at the second timepoint compared to the first.
Measured: Measured through Week 24 (Step 3)
Weight Z-scores of Virally Suppressed Children Receiving bNAbs
WHO standardized Z-scores will be evaluated for changes over time: WHO Weight-for-age z-score (0-10 yrs), Change from Step 1, Day 0 to Step 3, Week 24. A z-score of 0 corresponds to the population mean. Scores above 0 indicate a participant's weight is above the mean, while a score below 0 indicates a participant's weight is below the mean. A positive change in z-score corresponds to a higher z-score at the second timepoint compared to the first.
Measured: Measured through Week 24 (Step 3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2018
- Study start17 Jun 2019
- Primary completion3 Dec 2021
- Study completion3 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Roger Shapiro, MD, MPH, Principal investigator, Harvard School of Public Health (HSPH)Daniel Kuritzkes, MD, Principal investigator, Brigham and Women's HospitalMathias Lichterfeld, MD, PhD, Principal investigator, Brigham and Women's Hospital/Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03707977
- Sponsor's protocol ID
- Tatelo Study
- Other IDs
- 38551
- Status last verified
- Jan 2023
- First submitted
- 12 Oct 2018
- Last updated
- 4 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 36094485Shapiro 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.
PubMed 37406137Banga 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.
PubMed 40136003Sakoi-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.
PubMed 38536810Niesar 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.
PubMed 41697750Ajibola 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.
PubMed 41078080