Dual bNAb Treatment in Children

HIV Infection Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03707977
• Other study ID #: Tatelo Study
• Secondary ID: 38551
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 17, 2019
• Est. completion date: December 3, 2021

Study information

• Verified date: January 2023
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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 In Step 2, ART is withdrawn and dual bNAb maintenance treatment occurs.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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 3, 2021
• Est. primary completion date: December 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 96 Weeks to 7 Years

Eligibility

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)

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Drug:
• ART
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.

Biological:
• VRC01LS
Administered by intravenous (IV) infusion
• 10-1074
Administered by intravenous (IV) infusion

Locations

Country	Name	City	State
Botswana	Francistown Non-Network CRS	Francistown
Botswana	Botswana Harvard AIDS Institute Partnership CRS Non-Network	Gaborone

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Botswana, 

References & Publications (1)

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, Kuritz — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	VRC01LS or 10-1074 Concentrations in Plasma	Median pre-dose trough (28 days post previous dose) based on laboratory evaluations	Measured through Week 12 (PK Step)
Secondary	Median Trough Concentration of VRC01LS or 10-1074 in Plasma 28 Days After the Third Dose	Based on laboratory evaluations	Measured through Week 12 (PK Step)
Secondary	VRC01LS and 10-1074 Concentrations in Plasma for Each Time Point	Based on laboratory evaluations	Measured through Week 32 following Step 1 entry
Secondary	Proportion of Children With Trough VRC01LS and 10-1074 Concentrations Below Defined Trough Ranges	Based on laboratory evaluations	Measured through Week 32 following Step 1 entry
Secondary	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 through Week 24 (Step 3)
Secondary	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 through Week 24 (Step 3)