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Early Neutralizing Antibodies in Infants Living With HIV to Enhance Their Life (2) (ENABLE 2)

12 giugno 2026 aggiornato da: Hospital Universitario 12 de Octubre

A Phase 1/2 Trial Evaluating the Safety, Pharmacokinetics, and Antiviral Activity of Subcutaneous ePGT121v1-LS in Combination With VRC07-523LS, Added to Standard Antiretroviral Therapy in Infants Living With HIV

The goal of this clinical trial is to learn if subcutaneous ePGT121v1-LS and VRC07-523-LS added to standard antiretroviral therapy (ART) is safe and helps improve HIV viral suppression in infants living with HIV in Mozambique and Cameroon. The study will also learn how the body processes ePGT121v1-LS and VRC07-523-LS and whether caregivers and health workers find this treatment approach acceptable.

The main questions it aims to answer are:

  • Are ePGT121v1-LS and and VRC07-523-LS safe and well tolerated in infants living with HIV?
  • Does adding ePGT121v1-LS and VRC07-523-LS to standard ART increase the number of infants who achieve HIV viral suppression by week 48?
  • How long does it take participants receiving ePGT121v1-LS and VRC07-523-LS to achieve viral suppression compared with standard treatment alone?
  • How does ePGT121v1-LS and VRC07-523-LS behave in the body after repeated subcutaneous injections?

Researchers will compare infants receiving ePGT121v1-LS and VRC07-523-LS plus ART to infants receiving standard ART plus placebo (saline) to see if ePGT121v1-LS improves HIV viral suppression.

Participants will:

  • Continue taking standard oral ART.
  • Receive 4 subcutaneous injections of ePGT121v1-LS and VRC07-523-LS or placebo every 12 weeks.
  • Attend regular clinic visits for safety checks, blood tests, and HIV viral load monitoring.
  • Have follow-up visits for 48 weeks.
  • Participate in evaluations of treatment adherence and acceptability from the perspective of caregivers and health workers.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

This Phase 1/2 clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of subcutaneous (SC) ePGT121v1-LS and VRC07-523-LS administered as adjunctive therapy to standard antiretroviral therapy (ART) in infants living with HIV (ILHIV) in South Africa.

Although early ART initiation has significantly improved survival among infants with HIV, achieving sustained virological suppression during infancy remains challenging because of factors including limited pediatric formulations, adherence difficulties, high baseline viral loads, and treatment interruptions. Novel long-acting therapeutic strategies that simplify treatment delivery and enhance antiviral activity may improve outcomes in this vulnerable population.

Broadly neutralizing antibodies (bNAbs) have shown antiviral activity in adults and children living with HIV and may provide additional benefits through prolonged antiviral coverage and immunomodulatory effects. ePGT121v1-LS is a long-acting bNAb directed against the V3 glycan supersite of the HIV-1 envelope and VRC07-523-LS is a bNAb against the CD4 binding site. The LS mutation extends antibody half-life and supports infrequent dosing schedules using SC administration.

This study includes an initial safety lead-in phase followed by a randomized placebo-controlled phase evaluating ePGT121v1-LS and VRC07-523-LS in combination with standard ART. The trial will assess the safety profile and tolerability of repeated SC administrations and will characterize pharmacokinetic parameters following serial dosing in infants. In addition, the study will evaluate the antiviral effect of ePGT121v1-LS and VRC07-523-LS intensification therapy on HIV viral suppression during the first 48 weeks of follow-up.

Exploratory analyses will further assess virological, immunological, and reservoir-related outcomes, including HIV-1 DNA dynamics, anti-drug antibodies, biomarkers and immune responses associated with bNAb exposure. Qualitative assessments will also evaluate the acceptability and feasibility of SC bNAb administration from the perspective of caregivers, healthcare workers, and stakeholders.

The results of this study are intended to inform the development of future pediatric trials evaluating long-acting bNAb-based therapeutic strategies for infants living with HIV.

Tipo di studio

Interventistico

Iscrizione (Stimato)

73

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Bambino

Accetta volontari sani

No

Descrizione

Inclusion Criteria:

  • Infants from 1 to 365 days old at the time of enrolment.
  • Living with HIV-1, diagnosed with an approved assay detecting HIV nucleic acids in blood.
  • Weight > 2.5 kg at enrolment.
  • ART-naïve or ≤ 30 days of triple ART at screening (not including prophylaxis in HIV-exposed).
  • Clinically stable and can be managed as outpatient (participants identified in-hospital can start the trial at their first routine visit).
  • Parent or legal guardian able to provide Informed consent (IC).

Exclusion Criteria:

  • Participation in other concurrent research studies that, in the opinion of the principal investigator and central team, would interfere with the objectives of this study.
  • Previous receipt of bNAbs against HIV.
  • Serious Adverse Reactions (SARs) to the investigational medicinal product (IMP) or its components.
  • Intravenous (IV) immunoglobulins received within 90 days before IMP administration.
  • Any clinically significant acute or chronic illness or condition at screening that, in the opinion of the principal investigator/designee, renders the participant unfit to participate in the study or jeopardizes the safety or rights of the participant. Including, but not restricted to:
  • Evidence of active tuberculosis (TB) disease at the time of enrolment.
  • Life-threatening condition associated with a high risk of death within 30 days of enrolment, as determined by the study clinician.
  • Severe acute malnutrition with complications.
  • Severe neurological illness.
  • Hemodynamically significant severe congenital heart disease.
  • Active malignancies.
  • Life-threatening bleeding disorder.
  • Use of systemic immunosuppressive drugs within 30 days before first IMP administration. Not exclusionary: nasal steroid spray, inhaled steroids, topical steroids, a single course of oral/parenteral prednisone or equivalent at 2 mg/kg/day, and length of therapy <14 days.
  • Unwillingness to have blood drawn
  • Unable to receive SC medications.
  • Chronic or recurrent urticaria or any other chronic dermatological condition that may be confused with local Adverse Reactions (ARs).

Any social or medical condition in the caregivers that, in the judgement of the investigator, would interfere with protocol adherence, completion of the trial or assessment of safety.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: ePGT121v1-LS and VRC07-523-LS
4 injections of the bNAb ePGT121v1-LS and 4 injections of and VRC07-523-LS, separated 12 weeks, plus antiretroviral treatment.
Droga: Broadly neutralizing antibody (bNAb) ePGT121v1-LS
Administration of subcutaneous ePGT121v1LS, 4 doses, separate 12 weeks away.
Droga: Broadly neutralizing antibody (bNAb) VRC07-523-LS
Administration of subcutaneous ePGT121v1LS, 4 doses, separate 12 weeks away.
Comparatore placebo: Placebo (saline)
4 injections of saline, separated 12 weeks, plus antiretroviral treatment.
Droga: Saline (0.9% NaCl)
Administration of subcutaneous saline, 4 doses, separate 12 weeks away.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Safety (Serious adverse events)
Lasso di tempo: 48 weeks
Proportion of participants experiencing SAEs throughout the whole trial.
48 weeks
Virological suppression
Lasso di tempo: 48 weeks
  • Proportion of infants achieving virological suppression (plasma HIV-1 RNA < 40 copies/mL) at week 48, as well as over the 48 week follow-up period.
  • Time to first virological suppression, defined as the time from randomization to the first post-baseline measurement of plasma HIV-1 RNA < 40 copies/mL.
48 weeks
Time to virological suppression
Lasso di tempo: 48 weeks
• Time to first virological suppression, defined as the time from randomization to the first post-baseline measurement of plasma HIV-1 RNA < 40 copies/mL.
48 weeks
Tolerability of the treatment (participants who discontinue)
Lasso di tempo: 48 weeks
• Proportion of participants who discontinue due to toxicity or tolerability issues.
48 weeks
Tolerability of the injection
Lasso di tempo: 1 hour
• Median score of pain assessment scale after administration of bNAb (FLACC scale).
1 hour

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
PK profile of ePGT121v1-LS and of VRC07-523-LS
Lasso di tempo: 12 weeks
Half-life
12 weeks
Time to sustained virological suppression
Lasso di tempo: 48 weeks
Time from randomization to the first scheduled post-baseline visit at which HIV-1 RNA is < 40 copies/mL, provided that all subsequent scheduled HIV-1 RNA measurements through week 48 also remain < 40 copies/mL.
48 weeks
Longitudinal virological response
Lasso di tempo: 48 weeks
Proportion of participants with HIV-1 RNA < 40 copies/mL at weeks 12, 24, 36, and 48 will be recorded as the endpoint and log change in plasma HIV-1 RNA levels relative to baseline and subsequent pre-dose measurements.
48 weeks
Acceptability
Lasso di tempo: 48 weeks
The acceptability will be assessed through a series of qualitative interviews and limited quantitative assessments.
48 weeks
Adverse events
Lasso di tempo: 48 weeks
Number of and proportion of participants with solicited adverse event (AEs) and laboratory-related AEs.
48 weeks

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
All-cause mortality and number of hospitalizations.
Lasso di tempo: 48 weeks
All-cause mortality and number of hospitalizations.
48 weeks
Clinical features at baseline and during follow-up
Lasso di tempo: 48 weeks
This exploratory objective will include a comprehensive evaluation of different clinical parameters such as demographics (age, gestational age, weight, Prevention of Mother-To-Child Transmission (PMTCT) interventions), HIV disease severity (VL, CD4+ T-cell count/percentage), nutritional status, comorbidities (infectious and non-infectious), and ART (time to initiation, adherence during follow-up).
48 weeks
HIV-1 DNA
Lasso di tempo: 48 weeks
The concentration of intact and defective HIV-1 proviral DNA, expressed as copies per million of peripheral blood mononuclear cells (PBMCs), measured by intact proviral DNA assay (IPDA) and quantified at baseline and week 48
48 weeks
Anti-drug antibodies (ADAs)
Lasso di tempo: 48 weeks
The titers of ADAs will be quantified at baseline and week 48 to assess whether the development of host antibodies (anti-bNAbs) contributes to virological failure among infants who experience viral rebound by week 48, compared to infants with virological suppression at week 48.
48 weeks
Neutralizing Activity
Lasso di tempo: 48 weeks
Neutralization titers will be calculated as IC50 (50% inhibitory concentration) and IC80 (80% inhibitory concentration) by TZM-bl luciferase reporter assay. In vitro susceptibility of env-pseudotyped viruses derived from all participants at baseline and from those experiencing breakthrough viremia at week 48 will be used to establish whether in vitro susceptibility predicts virological success
48 weeks
Immunophenotype
Lasso di tempo: 48 weeks
Cellular immunophenotype will be measured using AIM-ICS flow cytometry to determine the activation status and cytokine production of T-cells and NK cells.
48 weeks
ADCC and intracellular p24 expression
Lasso di tempo: 24 weeks
Change from baseline in bNAb-mediated effector function, as measured by ADCC assays, quantified by percentage of target cell lysis and percentage of activated NK cells (e.g., CD107a+) at predefined timepoints.
24 weeks
Biomarkers
Lasso di tempo: 48 weeks
Association between sTREM-1 and adverse outcomes (mortality)
48 weeks

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Hospital Universitario 12 de Octubre

Collaboratori

University of Rome Tor Vergata
International AIDS Vaccine Initiative
University of Witwatersrand, South Africa
PENTA Foundation
Centro de Investigação em Saúde de Manhiça
Barcelona Institute for Global Health
Eduardo Mondlane University
Africa Health Research Institute
Faculty of Medical Sciences, Radboud University of Medical Center
Centre Pasteur du Cameroun
Servicio Madrileño de Salud (SERMAS)
Fundaçao Ariel Glaser contra o SIDA Pediatrico

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 gennaio 2027

Completamento primario (Stimato)

1 luglio 2029

Completamento dello studio (Stimato)

31 dicembre 2029

Date di iscrizione allo studio

Primo inviato

9 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

12 giugno 2026

Primo Inserito (Effettivo)

17 giugno 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

17 giugno 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

12 giugno 2026

Ultimo verificato

1 giugno 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 101190620_2

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano IPD

The individual de-identified participant data (including data dictionary), statistical code, and any other materials will be accessible after the end of the project in an open repository upon request.

Periodo di condivisione IPD

The individual de-identified participant data (including data dictionary), statistical code, and any other materials will be accessible after the end of the project in an open repository upon request.

Criteri di accesso alla condivisione IPD

Upon reasonable request.

Tipo di informazioni di supporto alla condivisione IPD

  • STUDIO_PROTOCOLLO
  • LINFA

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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