HIV -1 InfectionPhase 1/2ENABLE 1NCT07655128
Early Neutralizing Antibodies in Infants Living With HIV to Enhance Their Life
A Phase 1/2 study testing Broadly neutralizing antibody (bNAb) ePGT121v1-LS and Saline (0.9% NaCl) in people with HIV -1 Infection, run by Hospital Universitario 12 de Octubre.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 day to 1 year
- Conditions the study is for
- HIV -1 Infection
- What is being tested?
- Broadly neutralizing antibody (bNAb) ePGT121v1-LS and Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 87 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2027to 31 Dec 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 1 year
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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
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:
Read more
- 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.
Read the 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.
- Conditions
- HIV -1 Infection
- Being tested
- Broadly neutralizing antibody (bNAb) ePGT121v1-LS, Saline (0.9% NaCl)
- Keywords
- HIV, broadly neutralizing antibody, ePGT121v1-LS, viral load, safety, infant, children
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Broadly neutralizing antibody (bNAb) ePGT121v1-LSDrug
Administration of subcutaneous ePGT121v1LS, 4 doses, separate 12 weeks away.
Saline (0.9% NaCl)Drug
Administration of subcutaneous saline, 4 doses, separate 12 weeks away.
| Study group | Role | What they receive |
|---|---|---|
| ePGT121v1-LS | Active comparator | 4 injections of the bNAb ePGT121v1-LS, separated 12 weeks, plus antiretroviral treatment. Receives: Drug: Broadly neutralizing antibody (bNAb) ePGT121v1-LS |
| Placebo (saline) | Placebo comparator | 4 injections of saline, separated 12 weeks, plus antiretroviral treatment. Receives: Drug: Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (Serious adverse events)
Proportion of participants experiencing SAEs throughout the whole trial.
Measured: 48 weeks
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.
Measured: 48 weeks
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.
Measured: 48 weeks
Tolerability of the treatment (participants who discontinue)
- Proportion of participants who discontinue due to toxicity or tolerability issues.
Measured: 48 weeks
Tolerability of the injection
- Median score of pain assessment scale after administration of bNAb (FLACC scale).
Measured: 1 hour
Secondary outcomes (5)
PK profile of ePGT121v1-LS
Half-life
Measured: 12 weeks
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.
Measured: 48 weeks
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.
Measured: 48 weeks
Acceptability
The acceptability will be assessed through a series of qualitative interviews and limited quantitative assessments.
Measured: 48 weeks
Adverse events
Number of and proportion of participants with solicited adverse event (AEs) and laboratory-related AEs.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2026
- Study start1 Jan 2027 (estimated)
- Primary completion1 Jul 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV -1 InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Step 1 (safety lead-in): Non-randomized single arm with ePGT121v1-LS on top of antiretroviral therapy (ART). Step 2 (safety and efficacy): Double blind, randomized, parallel group with ePGT121v1-LS on top of ART compared to oral ART and placebo (saline).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 87 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario 12 de Octubre
- Sponsor type
- University, hospital or other
- Collaborators
- University of Stellenbosch, Africa Health Research Institute, PENTA Foundation, International AIDS Vaccine Initiative, University of Witwatersrand, South Africa, Enhancing Care Foundation, Radboud University Medical Center, Servicio Madrileño de Salud (SERMAS)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07655128
- Sponsor's protocol ID
- 101190620_1
- Acronym
- ENABLE 1
- Status last verified
- Aug 2026
- First submitted
- 9 Jun 2026
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07655128
- Acronym / sponsor ID
- ENABLE 1 / 101190620_1
- Conditions
- HIV -1 Infection
- Keywords
- HIV, broadly neutralizing antibody, ePGT121v1-LS, viral load, safety, infant, children
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 87 participants (estimated)
- Lead sponsor
- Hospital Universitario 12 de OctubreUniversity, hospital or other
- Collaborators
- University of Stellenbosch, Africa Health Research Institute, PENTA Foundation, International AIDS Vaccine Initiative, University of Witwatersrand, South Africa, Enhancing Care Foundation, Radboud University Medical Center, Servicio Madrileño de Salud (SERMAS)
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 1 Jul 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 17 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Step 1 (safety lead-in): Non-randomized single arm with ePGT121v1-LS on top of antiretroviral therapy (ART). Step 2 (safety and efficacy): Double blind, randomized, parallel group with ePGT121v1-LS on top of ART compared to oral ART and placebo (saline).
| Arm | Type | Receives |
|---|---|---|
| ePGT121v1-LS | Active comparator | Drug: Broadly neutralizing antibody (bNAb) ePGT121v1-LS4 injections of the bNAb ePGT121v1-LS, separated 12 weeks, plus antiretroviral treatment. |
| Placebo (saline) | Placebo comparator | Drug: Saline (0.9% NaCl)4 injections of saline, separated 12 weeks, plus antiretroviral treatment. |
Who may qualify
- Ages
- 1 day to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (17 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Broadly neutralizing antibody (bNAb) ePGT121v1-LSAdministration of subcutaneous ePGT121v1LS, 4 doses, separate 12 weeks away. | Drug | ePGT121v1-LS |
| Saline (0.9% NaCl)Administration of subcutaneous saline, 4 doses, separate 12 weeks away. | Drug | Placebo (saline) |
Primary outcome
Safety (Serious adverse events)
Time frame: 48 weeks
Proportion of participants experiencing SAEs throughout the whole trial.
Virological suppression (snapshot)
Time frame: 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 virological suppression
Time frame: 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.
Tolerability of the treatment (participants who discontinue)
Time frame: 48 weeks
• Proportion of participants who discontinue due to toxicity or tolerability issues.
Tolerability of the injection
Time frame: 1 hour
• Median score of pain assessment scale after administration of bNAb (FLACC scale).
5 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Broadly neutralizing antibody (bNAb) ePGT121v1-LS and Saline (0.9% NaCl) in people with HIV -1 Infection, run by Hospital Universitario 12 de Octubre.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alfredo Tagarro, PhD (+34606194888, alfredo.tagarro@salud.madrid.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (Serious adverse events) (time frame: 48 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026.