The Tatelo Plus Study

Phase 1

Recruiting

• Conditions: HIV; HIV Infections
• Interventions: Drug: PGDM1400LS; Other: Analytic Treatment Interruption; 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

• Registration Number: NCT06508749
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2024-06-26
• Study First Submitted QC: 2024-07-12
• Study First Posted: 2024-07-18
• Status Verified: 2024-11
• Study Start: 2024-11-11
• Last Update Submitted: 2024-11-18
• Last Update Posted: 2024-11-20
• Primary Completion: 2028-02-25
• Study Completion: 2028-02-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

Not provided

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Step 2b	PGDM1400LS	In Step 2b participants remain off ART and continue to receive three bNAbs administered on a rotating schedule.
Step 1b Entry	PGDM1400LS	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.
Group 1-Step 1a Entry	VRC07-523LS	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.
Group 1-Step 1a Entry	ART Regimen prior to enrolling in Step 1a	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.
Group 2-Step 1a Entry	PGDM1400LS	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.
Group 2-Step 1a Entry	VRC07-523LS	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.
Group 1-Step 1a Entry	PGT121.414.LS	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.
Group 2-Step 1a Entry	PGT121.414.LS	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.
Group 2-Step 1a Entry	ART Regimen prior to enrolling in Step 1a	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.
Step 2b	VRC07-523LS	In Step 2b participants remain off ART and continue to receive three bNAbs administered on a rotating schedule.
Group 1-Step 1a Entry	PGDM1400LS	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.
Step 2a	PGDM1400LS	In Step 2a participants discontinue ART and receive three bNAbs administered on a rotating schedule.
Step 2a	VRC07-523LS	In Step 2a participants discontinue ART and receive three bNAbs administered on a rotating schedule.
Step 1b Entry	VRC07-523LS	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.
Step 2a	PGT121.414.LS	In Step 2a participants discontinue ART and receive three bNAbs administered on a rotating schedule.
Group 3- Step 3 Direct Entry	Analytic Treatment Interruption	ATI Only. Participants discontinue ART. For anyone directly enrolling in the Step 3 ATI and not participating in Steps 1 or 2
Step 1b Entry	PGT121.414.LS	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.
Step 1b Entry	ART Regimen prior to enrolling in Step 1b	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.
Step 2b	PGT121.414.LS	In Step 2b participants remain off ART and continue to receive three bNAbs administered on a rotating schedule.
Step 3 progression	Analytic Treatment Interruption	ATI Only. Participants discontinue ART and bNAbs. For participants progressing to Step 3 after participating in Steps 1 and 2

Primary Outcome Measures

Name	Time	Method
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	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	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	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	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	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	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 Outcome Measures

Name	Time	Method
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	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)
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	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.
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	Time to viral re-suppression defined as first HIV-1 RNA \<40 copies/mL following ART resumption

Trial Locations

Locations (2)

Francistown CRS (CRS #31891); 🇧🇼 Francistown, Botswana

Botswana Harvard Health Partnership CRS (CRS #31833); 🇧🇼 Gaborone, Botswana