Phase I/II Trial to Evaluate the Impact of Three Broadly Neutralizing Antibodies or Analytic Treatment Interruption on Viral Reservoir, Immune Function, and Maintenance of HIV Suppression in Early Treated Children in Botswana
Overview
- Phase
- Phase 1
- Intervention
- PGDM1400LS
- Conditions
- HIV
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 41
- Locations
- 2
- Primary Endpoint
- To describe the safety and pharmacokinetics of bNAb immunotherapy with VRC07-523LS, PGDM1400LS and PGT121.414.LS when added to existing effective ART in early-treated children living with HIV-1 in Botswana
- Status
- Recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
The purpose of this study is to advance pediatric HIV treatment and cure research by evaluating the impact of a combination of three anti-HIV-1 broadly neutralizing antibodies (bNAbs) or analytic treatment interruption (ATI) on viral reservoir, immune function, and maintenance of HIV suppression in early-treated children.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Active tuberculosis (either suspected or proven) or malignancy.
- •Hepatitis B surface antigen (HBsAg) positive
- •Received within 30 days prior to study entry, or is identified as requiring, any of the following:
- •Any immunoglobulin-based treatment
- •Chronic (more than 14 days) systemic steroid treatment
- •Has any other documented or suspected clinically significant medical condition or any other condition that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
- •For participants entering Step 1 and Step 2: \<5 kg or \>115kg.
- •For participants entering Step 3 directly: Received NNRTI-based ART (including efavirenz, nevirapine, rilpivirine) within 14 days of Step 3 entry
Arms & Interventions
Group 1-Step 1a Entry
Receiving PGDM1400LS first Step 1a includes a single-agent safety lead-in period for PGDM1400LS (Group 1), followed by three bNAbs administered on a rotating schedule while participants continue to receive ART. A pharmacokinetic assessment will be conducted for the three bNAbs.
Intervention: PGDM1400LS
Group 1-Step 1a Entry
Receiving PGDM1400LS first Step 1a includes a single-agent safety lead-in period for PGDM1400LS (Group 1), followed by three bNAbs administered on a rotating schedule while participants continue to receive ART. A pharmacokinetic assessment will be conducted for the three bNAbs.
Intervention: VRC07-523LS
Group 1-Step 1a Entry
Receiving PGDM1400LS first Step 1a includes a single-agent safety lead-in period for PGDM1400LS (Group 1), followed by three bNAbs administered on a rotating schedule while participants continue to receive ART. A pharmacokinetic assessment will be conducted for the three bNAbs.
Intervention: PGT121.414.LS
Group 1-Step 1a Entry
Receiving PGDM1400LS first Step 1a includes a single-agent safety lead-in period for PGDM1400LS (Group 1), followed by three bNAbs administered on a rotating schedule while participants continue to receive ART. A pharmacokinetic assessment will be conducted for the three bNAbs.
Intervention: ART Regimen prior to enrolling in Step 1a
Group 2-Step 1a Entry
Receiving PGT121.414.LS first Step 1a includes a single-agent safety lead-in period for PGT121.414.LS (Group 2), followed by three bNAbs administered on a rotating schedule while participants continue to receive ART. A pharmacokinetic assessment will be conducted for the three bNAbs.
Intervention: PGDM1400LS
Group 2-Step 1a Entry
Receiving PGT121.414.LS first Step 1a includes a single-agent safety lead-in period for PGT121.414.LS (Group 2), followed by three bNAbs administered on a rotating schedule while participants continue to receive ART. A pharmacokinetic assessment will be conducted for the three bNAbs.
Intervention: VRC07-523LS
Group 2-Step 1a Entry
Receiving PGT121.414.LS first Step 1a includes a single-agent safety lead-in period for PGT121.414.LS (Group 2), followed by three bNAbs administered on a rotating schedule while participants continue to receive ART. A pharmacokinetic assessment will be conducted for the three bNAbs.
Intervention: PGT121.414.LS
Group 2-Step 1a Entry
Receiving PGT121.414.LS first Step 1a includes a single-agent safety lead-in period for PGT121.414.LS (Group 2), followed by three bNAbs administered on a rotating schedule while participants continue to receive ART. A pharmacokinetic assessment will be conducted for the three bNAbs.
Intervention: ART Regimen prior to enrolling in Step 1a
Step 1b Entry
ATI Only. For anyone directly enrolling in the Step 3 ATI and not participating in Steps 1 or 2 In Step 1b participants receive three bNAbs administered on a rotating schedule while continuing to receive ART.
Intervention: PGDM1400LS
Step 1b Entry
ATI Only. For anyone directly enrolling in the Step 3 ATI and not participating in Steps 1 or 2 In Step 1b participants receive three bNAbs administered on a rotating schedule while continuing to receive ART.
Intervention: VRC07-523LS
Step 1b Entry
ATI Only. For anyone directly enrolling in the Step 3 ATI and not participating in Steps 1 or 2 In Step 1b participants receive three bNAbs administered on a rotating schedule while continuing to receive ART.
Intervention: PGT121.414.LS
Step 1b Entry
ATI Only. For anyone directly enrolling in the Step 3 ATI and not participating in Steps 1 or 2 In Step 1b participants receive three bNAbs administered on a rotating schedule while continuing to receive ART.
Intervention: ART Regimen prior to enrolling in Step 1b
Step 2a
In Step 2a participants discontinue ART and receive three bNAbs administered on a rotating schedule.
Intervention: PGDM1400LS
Step 2a
In Step 2a participants discontinue ART and receive three bNAbs administered on a rotating schedule.
Intervention: VRC07-523LS
Step 2a
In Step 2a participants discontinue ART and receive three bNAbs administered on a rotating schedule.
Intervention: PGT121.414.LS
Step 2b
In Step 2b participants remain off ART and continue to receive three bNAbs administered on a rotating schedule.
Intervention: PGDM1400LS
Step 2b
In Step 2b participants remain off ART and continue to receive three bNAbs administered on a rotating schedule.
Intervention: VRC07-523LS
Step 2b
In Step 2b participants remain off ART and continue to receive three bNAbs administered on a rotating schedule.
Intervention: PGT121.414.LS
Step 3 progression
ATI Only. Participants discontinue ART and bNAbs. For participants progressing to Step 3 after participating in Steps 1 and 2
Intervention: Analytic Treatment Interruption
Group 3- Step 3 Direct Entry
ATI Only. Participants discontinue ART. For anyone directly enrolling in the Step 3 ATI and not participating in Steps 1 or 2
Intervention: Analytic Treatment Interruption
Outcomes
Primary Outcomes
To describe the safety and pharmacokinetics of bNAb immunotherapy with VRC07-523LS, PGDM1400LS and PGT121.414.LS when added to existing effective ART in early-treated children living with HIV-1 in Botswana
Time Frame: Through week 32
Occurrence of Grade 3 or higher adverse events Occurrence of Grade 1 or higher bNAb-related adverse events Occurrence of any SAE Permanent discontinuation of study product Pre-dose trough concentrations of VRC07-523LS, PGDM1400LS and PGT121.414.LS at Week 16 Pre-dose trough concentrations of VRC07-523LS, PGDM1400LS and PGT121.414.LS through 32 weeks
To describe the safety of up to 24 weeks of bNAb immunotherapy with VRC07-523LS, PGDM1400LS and PGT121.414.LS when added on a rotating schedule to existing effective ART in early-treated children living with HIV-1 in Botswana
Time Frame: Through week 24
Occurrence of Grade 3 or higher adverse events Occurrence of Grade 1 or higher bNAb-related adverse events Occurrence of any SAE Permanent discontinuation of study product
To determine the CD4 cell count preservation of 24 weeks of maintenance VRC07-523LS, PGDM1400LS and PGT121.414.LS immunotherapy alone, following the discontinuation of ART
Time Frame: Through Week 24
Change in absolute CD4 cell count
To determine the safety of 24 weeks of maintenance VRC07-523LS, PGDM1400LS and PGT121.414.LS immunotherapy alone, following the discontinuation of ART
Time Frame: Through Week 24
Occurrence of Grade 3 or higher adverse events Occurrence of Grade 1 or higher bNAb-related adverse events
To determine the maintenance of virologic suppression of 24 weeks of maintenance VRC07-523LS, PGDM1400LS and PGT121.414.LS immunotherapy alone, following the discontinuation of ART
Time Frame: Through Week 24
Viral rebound defined as plasma HIV-1 RNA ≥400 copies/mL at or prior to 24 weeks of bNAb-only treatment.
To describe the safety, maintenance of virologic suppression, and CD4 cell count preservation of up to 48 weeks of ATI (with no ART or bNAbs) among participants who meet specified criteria for an ATI
Time Frame: Through Week 48
Occurrence of Grade 3 or higher adverse events Occurrence of Grade 1 or higher ATI-related adverse events Viral rebound defined as plasma HIV-1 RNA ≥400 copies/mL at or prior to 48 weeks of ATI Change in absolute CD4 cell count
Secondary Outcomes
- To measure the proportion of participants with viral rebound defined as a single plasma HIV-1 RNA ≥400 copies/mL at or prior to 48 weeks of bNAb-only treatment (for those who continue bNAb-only treatment beyond 24 weeks)(Through week 48)
- To measure the size of residual viral reservoirs, during each step of the study. Comparisons will include change during triple bNAbs + ART; change during triple bNAbs alone; change during ATI; and change during entire study(Through week 48)
- To monitor and report time to re-suppression of plasma HIV-1 RNA following re-initiation of ART, for participants who experience viral rebound on bNAbs alone or during ATI(Through week 48)