The Tatelo Plus Study
NCT Number: NCT06508749
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: HIV|HIV Infections
Interventions: DRUG: PGDM1400LS|DRUG: VRC07-523LS|DRUG: PGT121.414.LS|DRUG: ART Regimen prior to enrolling in Step 1a|DRUG: ART Regimen prior to enrolling in Step 1b|OTHER: Analytic Treatment Interruption
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sex: ALL
Age: CHILD, ADULT
Enrollment: 41
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-06
Completion Date: 2028-02-25
Locations: Francistown CRS (CRS #31891), Francistown, Botswana|Botswana Harvard Health Partnership CRS (CRS #31833), Gaborone, Botswana

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.

Primary Outcome Measures: 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, 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, Through week 32|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, 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, Through week 24|To determine the safety of 24 weeks of maintenance VRC07-523LS, PGDM1400LS and PGT121.414.LS immunotherapy alone, following the discontinuation of ART, Occurrence of Grade 3 or higher adverse events Occurrence of Grade 1 or higher bNAb-related adverse events, Through Week 24|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, Viral rebound defined as plasma HIV-1 RNA ≥400 copies/mL at or prior to 24 weeks of bNAb-only treatment., Through Week 24|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, Change in absolute CD4 cell count, Through Week 24|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, 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, Through Week 48
Secondary Outcome Measures: 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), Viral rebound defined as plasma HIV-1 RNA ≥400 copies/mL at or prior to 48 weeks of bNAb-only treatment (among participants who continue beyond 24 weeks on bNAb-only treatment), 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, Time to viral re-suppression defined as first HIV-1 RNA \<40 copies/mL following ART resumption, 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, Change in total, intact, and defective provirus between entry and end of triple bNAbs + ART Change in total, intact, and defective provirus between start of bNAb-only treatment and end of bNAb-only treatment Change in total, intact, and defective provirus between start of ATI and end of ATI.

Change in total, intact, and defective provirus between study entry and end of ATI., Through week 48