The goal of this clinical trial is to learn if subcutaneous ePGT121v1-LS added to standard antiretroviral therapy (ART) is safe and helps improve HIV viral suppression in infants living with HIV in South Africa. The study will also learn how the body processes ePGT121v1-LS and whether caregivers and health workers find this treatment approach acceptable.
The main questions it aims to answer are:
* Is ePGT121v1-LS safe and well tolerated in infants living with HIV? * Does adding ePGT121v1-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 to achieve viral suppression compared with standard treatment alone? * How does ePGT121v1-LS behave in the body after repeated subcutaneous injections?
Researchers will compare infants receiving ePGT121v1-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 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.
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).
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.
Parallel
Broadly neutralizing antibody (bNAb) ePGT121v1-LS
DrugAdministration of subcutaneous ePGT121v1LS, 4 doses, separate 12 weeks away.
Saline (0.9% NaCl)
DrugAdministration of subcutaneous saline, 4 doses, separate 12 weeks away.
Safety (Serious adverse events)
Proportion of participants experiencing SAEs throughout the whole trial.
Virological suppression (snapshot)
• 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 virological suppression
• 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.
Tolerability of the treatment (participants who discontinue)
• Proportion of participants who discontinue due to toxicity or tolerability issues.
PK profile of ePGT121v1-LS
Half-life
Time to sustained virological suppression
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.
Longitudinal virological response
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.
Acceptability
The acceptability will be assessed through a series of qualitative interviews and limited quantitative assessments.
All-cause mortality and number of hospitalizations.
All-cause mortality and number of hospitalizations.
Clinical features at baseline and during follow-up
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).
HIV-1 DNA
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
Anti-drug antibodies (ADAs)
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.
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Hospital Universitario 12 de Octubre
Lead sponsor
University of Stellenbosch
Collaborator
Africa Health Research Institute
Collaborator
PENTA Foundation
Collaborator
International AIDS Vaccine Initiative
Collaborator
University of Witwatersrand, South Africa
Collaborator
Enhancing Care Foundation
Collaborator
Radboud University Medical Center
Collaborator
Servicio Madrileño de Salud (SERMAS)
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
