Early Neutralizing Antibodies in Infants Living With HIV to Enhance Their Life

Official title

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

Overview

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.

Detailed description

This Phase 1/2 clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of subcutaneous (SC) ePGT121v1-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. 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 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 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, viral diversity, neutralization sensitivity, anti-drug antibodies, 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.

Interventions

• Drug Broadly neutralizing antibody (bNAb) ePGT121v1-LS
  Administration of subcutaneous ePGT121v1LS, 4 doses, separate 12 weeks away.
• Drug Saline (0.9% NaCl)
  Administration of subcutaneous saline, 4 doses, separate 12 weeks away.

Primary outcome measures

• Safety (Serious adverse events) [Time frame: 48 weeks]
• Virological suppression (snapshot) [Time frame: 48 weeks]
• Time to virological suppression [Time frame: 48 weeks]
• Tolerability of the treatment (participants who discontinue) [Time frame: 48 weeks]
• Tolerability of the injection [Time frame: 1 hour]

Secondary outcome measures (5)

• PK profile of ePGT121v1-LS [Time frame: 12 weeks]
• Time to sustained virological suppression [Time frame: 48 weeks]
• Longitudinal virological response [Time frame: 48 weeks]
• Acceptability [Time frame: 48 weeks]
• Adverse events [Time frame: 48 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07655128 · 101190620_1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗