The Tatelo Plus Study

NCT06508749 | Recruiting Phase 1 FDA Drug

• 1 other identifier: IMPAACT 2042
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV; HIV Infections

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• 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 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

• 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

Study Arms (7)

Group 1-Step 1a Entry

EXPERIMENTAL

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.

Drug: PGDM1400LS; Drug: VRC07-523LS; Drug: PGT121.414.LS; Drug: ART Regimen prior to enrolling in Step 1a

Group 2-Step 1a Entry

EXPERIMENTAL

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.

Drug: PGDM1400LS; Drug: VRC07-523LS; Drug: PGT121.414.LS; Drug: ART Regimen prior to enrolling in Step 1a

Step 1b Entry

EXPERIMENTAL

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.

Drug: PGDM1400LS; Drug: VRC07-523LS; Drug: PGT121.414.LS; Drug: ART Regimen prior to enrolling in Step 1b

Step 2a

EXPERIMENTAL

In Step 2a participants discontinue ART and receive three bNAbs administered on a rotating schedule.

Drug: PGDM1400LS; Drug: VRC07-523LS; Drug: PGT121.414.LS

Step 2b

EXPERIMENTAL

In Step 2b participants remain off ART and continue to receive three bNAbs administered on a rotating schedule.

Drug: PGDM1400LS; Drug: VRC07-523LS; Drug: PGT121.414.LS

Step 3 progression

EXPERIMENTAL

ATI Only. Participants discontinue ART and bNAbs. For participants progressing to Step 3 after participating in Steps 1 and 2

Other: Analytic Treatment Interruption

Group 3- Step 3 Direct Entry

EXPERIMENTAL

ATI Only. Participants discontinue ART. For anyone directly enrolling in the Step 3 ATI and not participating in Steps 1 or 2

Other: Analytic Treatment Interruption

Interventions

PGDM1400LS DRUG

IV Antibody Infusion based on subject's weight

Group 1-Step 1a Entry; Group 2-Step 1a Entry; Step 1b Entry; Step 2a; Step 2b

VRC07-523LS DRUG

IV Antibody Infusion based on subject's weight

Group 1-Step 1a Entry; Group 2-Step 1a Entry; Step 1b Entry; Step 2a; Step 2b

PGT121.414.LS DRUG

IV Antibody Infusion based on subject's weight

Group 1-Step 1a Entry; Group 2-Step 1a Entry; Step 1b Entry; Step 2a; Step 2b

ART Regimen prior to enrolling in Step 1a DRUG

Antiviral drugs are not study product. However, participants will continue to receive the ART regimen they were receiving prior to enrolling in the study during Step 1a.

Group 1-Step 1a Entry; Group 2-Step 1a Entry

ART Regimen prior to enrolling in Step 1b DRUG

Antiviral drugs are not study product. However, participants will continue to receive the ART regimen they were receiving prior to enrolling in the study during Step 1b.

Step 1b Entry

Analytic Treatment Interruption OTHER

(all anti-HIV agents are discontinued)

Group 3- Step 3 Direct Entry; Step 3 progression

Eligibility Criteria

• Age: 24 Weeks - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Previously enrolled in the EIT/Tatelo, or Moso Cohort Study
• Receiving prescribed ART for at least 24 weeks prior to study entry as determined by the site investigator based on participant/parent/guardian report and available medical records
• weeks to 12 years of age at enrollment, inclusive
• If entering Step 1a: HIV-1 RNA \<40 copies/mL for at least 24 weeks prior to entry, including documented suppression to \<40 copies/mL within 30 days of Step 1 entry
• If entering Step 1b: HIV-1 RNA \<200 copies/mL for at least 24 weeks prior to entry, including documented suppression to \<40 copies/mL within 30 days of Step 1 entry.
• Normal temperature (\<37.4°C axillary, or \<38°C non-axillary) and no signs or symptoms of acute illness at entry as determined by the site investigator based on participant/parent/guardian report and available medical records
• Normal, grade 1 or grade 2 results for all of the following laboratory tests at screening, based on testing of specimens collected within 30 days prior to entry and grading per protocol:
• Hemoglobin
• Absolute neutrophil count
• Platelet count
• Alanine aminotransferase
• Aspartate aminotransferase
• Creatinine
• For female participants who are able to become pregnant (defined as having reached menarche and not having undergone surgical sterilization), not pregnant based on testing performed from a specimen collected within 5 days prior to enrollment). Note: Pregnancy is not expected in Step 1 given the age range of eligible participants.
• Expected to be available for the duration of participation and expected to comply with the visit schedule and other requirements as determined by the site investigator based on participant/parent/guardian report at entry

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

Francistown CRS (CRS #31891)

Francistown, Botswana

RECRUITING

Botswana Harvard Health Partnership CRS (CRS #31833)

Gaborone, Botswana

RECRUITING

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Central Study Contacts

Molly Pretorius Holme, MSc

CONTACT

617-432-4377; mpretori@hsph.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2024
• First Posted: July 18, 2024
• Study Start: November 11, 2024
• Primary Completion (Estimated): November 5, 2027
• Study Completion (Estimated): April 21, 2028
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• Access Criteria: Researchers who provide a methodologically sound proposal for use of the data that is approved by the protocol leadership. * For what types of analyses? * To achieve aims in the proposal approved by the protocol leadership. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https:// www.impaactnetwork.org/ resources/study-proposals.htm. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.

Locations

BO (2)