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

12 de junio de 2026 actualizado por: 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.

Descripción general del estudio

Estado

Aún no reclutando

Condiciones

Intervención / Tratamiento

Descripción detallada

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 de estudio

Intervencionista

Inscripción (Estimado)

73

Fase

  • Fase 2
  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Niño

Acepta Voluntarios Saludables

No

Descripción

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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Doble

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: 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.
Comparador de placebos: 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.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Safety (Serious adverse events)
Periodo de tiempo: 48 weeks
Proportion of participants experiencing SAEs throughout the whole trial.
48 weeks
Virological suppression
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 48 weeks
• Proportion of participants who discontinue due to toxicity or tolerability issues.
48 weeks
Tolerability of the injection
Periodo de tiempo: 1 hour
• Median score of pain assessment scale after administration of bNAb (FLACC scale).
1 hour

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
PK profile of ePGT121v1-LS and of VRC07-523-LS
Periodo de tiempo: 12 weeks
Half-life
12 weeks
Time to sustained virological suppression
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 48 weeks
The acceptability will be assessed through a series of qualitative interviews and limited quantitative assessments.
48 weeks
Adverse events
Periodo de tiempo: 48 weeks
Number of and proportion of participants with solicited adverse event (AEs) and laboratory-related AEs.
48 weeks

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
All-cause mortality and number of hospitalizations.
Periodo de tiempo: 48 weeks
All-cause mortality and number of hospitalizations.
48 weeks
Clinical features at baseline and during follow-up
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 48 weeks
Association between sTREM-1 and adverse outcomes (mortality)
48 weeks

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Hospital Universitario 12 de Octubre

Colaboradores

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

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Estimado)

1 de enero de 2027

Finalización primaria (Estimado)

1 de julio de 2029

Finalización del estudio (Estimado)

31 de diciembre de 2029

Fechas de registro del estudio

Enviado por primera vez

9 de junio de 2026

Primero enviado que cumplió con los criterios de control de calidad

12 de junio de 2026

Publicado por primera vez (Actual)

17 de junio de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

17 de junio de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

12 de junio de 2026

Última verificación

1 de junio de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • 101190620_2

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

SÍ

Descripción del plan 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.

Marco de tiempo para compartir 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.

Criterios de acceso compartido de IPD

Upon reasonable request.

Tipo de información de apoyo para compartir IPD

  • PROTOCOLO DE ESTUDIO
  • SAVIA

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Sí

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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