Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202607574273305 Date of Registration: 03/07/2026
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Early Neutralizing Antibodies in Infants Living With HIV to Enhance Their Life 1
Official scientific 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
Brief summary describing the background and objectives of the trial Infants living with HIV remain at high risk of morbidity, mortality, and delayed virological suppression during the first year of life despite early initiation of standard antiretroviral therapy (ART). Additional therapeutic strategies are needed to achieve faster and more sustained viral control during this vulnerable period. Broadly neutralizing antibodies (bNAbs) are a promising adjunct to ART because they can neutralize diverse HIV-1 strains, may enhance clearance of infected cells, and could contribute to reducing viral replication and reservoir size. ePGT121v1-LS is a long-acting, V3 glycan-targeting bNAb being evaluated as an adjunctive treatment in infants living with HIV. ENABLE 1 is a phase 1/2 clinical trial in South Africa designed to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of subcutaneous ePGT121v1-LS added to standard ART in infants younger than 365 days living with HIV. The trial has two sequential phases. Step 1 is a non-randomized safety lead-in phase enrolling 11 infants, all of whom receive ePGT121v1-LS plus standard ART, to assess initial safety and tolerability. Step 2 is a single-blind randomized controlled phase enrolling 76 infants, randomized 1:1 to receive either ePGT121v1-LS plus standard ART or placebo plus standard ART. The total planned sample size is 87 infants. The primary objectives are to evaluate the safety and tolerability of four subcutaneous doses of ePGT121v1-LS administered every 12 weeks in combination with ART, and to assess its antiviral activity by comparing virological suppression outcomes between study arms through 48 weeks of follow-up. Secondary objectives include characterization of the pharmacokinetic profile of ePGT121v1-LS, assessment of longitudinal virological responses, and description of adverse events and serious adverse events. Exploratory objectives include mortality, hospitalizations, reservoir, anti-drug antibodies, viral sequencing, neutralization, and acceptability.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ENABLE
Disease(s) or condition(s) being studied Infections and Infestations,Paediatrics
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/01/2027
Actual trial start date
Anticipated date of last follow up 30/06/2029
Actual Last follow-up date
Anticipated target sample size (number of participants) 87
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group ePGT121v1LS 100 mg every 12 weeks. 48 weeks 4 injections of the bNAb ePGT121v1-LS, separated 12 weeks, plus antiretroviral treatment. The trial has two sequential phases. Step 1 is a non-randomized safety lead-in phase enrolling 11 infants, all of whom receive ePGT121v1-LS plus standard ART, to assess initial safety and tolerability. Step 2 is a single-blind randomized controlled phase enrolling 76 infants (38 in the intervention group and 38 in the control group) randomized 1:1 to receive either ePGT121v1-LS plus standard ART or placebo plus standard ART. The total planned sample size is 87 infants. 49
Control Group Saline 0.8 mL of saline every 12 weeks 48 weeks 4 injections of saline, separated 12 weeks, plus antiretroviral treatment. 38 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• 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 provides Informed consent (IC). • 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. Infant: 1 Month(s)-12 Month(s),New born: 0 Day-1 Month 1 Day(s) 1 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 10/07/2026 Stellenbosch University Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Room 3034, 3rd Floor, Clinical Building, Tygerberg Campus Cape Town 7505 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety (Serious adverse events) Proportion of participants experiencing SAEs throughout the whole trial. 48 weeks after randomization and first administration of IMP
Primary Outcome 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. 48 weeks after randomization and first administration of IMP
Primary Outcome 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. 48 weeks after randomization and first administration of IMP
Primary Outcome Tolerability of the treatment (participants who discontinue) • Proportion of participants who discontinue due to toxicity or tolerability issues. 48 weeks after randomization and first administration of IMP
Primary Outcome Tolerability of the injection • Median score of pain assessment scale after administration of bNAb (FLACC scale). 1 hour after administration of the IMP
Secondary Outcome PK profile of ePGT121v1-LS Half-life 12 weeks after randomization and first administration of IMP
Secondary Outcome 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. 48 weeks after randomization and first administration of IMP
Secondary Outcome 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. 48 weeks after randomization and first administration of IMP
Secondary Outcome Acceptability The acceptability will be assessed through a series of qualitative interviews and limited quantitative assessments. 48 weeks after randomization and first administration of IMP
Secondary Outcome Adverse events Number of and proportion of participants with solicited adverse event (AEs) and laboratory-related AEs. 48 weeks after randomization and first administration of IMP
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Stellenbosch University Tygerberg Academic HospitalFrancie van Zijl DriveParow Valley Cape Town 7505 South Africa
Enhancing Care Foundation 16 Charles Strachan Road, Westridge Durban South Africa
Wits University 1 Jan Smuts Ave, Braamfontein Johannesburg South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP Anna van Saksenlaan 51, 2593 HW Le Hague 2593 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor SERMAS Fundacion Hospital 12 de Octubre Avenida de Cordoba s/n Madrid Spain Hospital
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Alfredo Tagarro alfredo.tagarro@salud.madrid.org +34606194888 Avenida de Cordoba s/n
City Postal code Country Position/Affiliation
Madrid Spain Clinical Researcher
Role Name Email Phone Street address
Public Enquiries Annabelle Gachet annabellegachetpm@gmail.com +33640587415 Avenida de Cordoba
City Postal code Country Position/Affiliation
Madrid Spain Project Manager
Role Name Email Phone Street address
Scientific Enquiries Alfredo Tagarro alfredotagarro@gmail.com +34606194888 Avenida de Cordoba
City Postal code Country Position/Affiliation
Madrid Spain Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
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 Protocol 1 year after completion date. Upon reasonable request
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 26/06/2026 Requested by the Registry to include background and detail sample size. 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 living with HIV remain at high risk of morbidity, mortality, and delayed virological suppression during the first year of life despite early initiation of standard antiretroviral therapy (ART). Additional therapeutic strategies are needed to achieve faster and more sustained viral control during this vulnerable period. Broadly neutralizing antibodies (bNAbs) are a promising adjunct to ART because they can neutralize diverse HIV-1 strains, may enhance clearance of infected cells, and could contribute to reducing viral replication and reservoir size. ePGT121v1-LS is a long-acting, V3 glycan-targeting bNAb being evaluated as an adjunctive treatment in infants living with HIV. ENABLE 1 is a phase 1/2 clinical trial in South Africa designed to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of subcutaneous ePGT121v1-LS added to standard ART in infants younger than 365 days living with HIV. The trial has two sequential phases. Step 1 is a non-randomized safety lead-in phase enrolling 11 infants, all of whom receive ePGT121v1-LS plus standard ART, to assess initial safety and tolerability. Step 2 is a single-blind randomized controlled phase enrolling 76 infants, randomized 1:1 to receive either ePGT121v1-LS plus standard ART or placebo plus standard ART. The total planned sample size is 87 infants. The primary objectives are to evaluate the safety and tolerability of four subcutaneous doses of ePGT121v1-LS administered every 12 weeks in combination with ART, and to assess its antiviral activity by comparing virological suppression outcomes between study arms through 48 weeks of follow-up. Secondary objectives include characterization of the pharmacokinetic profile of ePGT121v1-LS, assessment of longitudinal virological responses, and description of adverse events and serious adverse events. Exploratory objectives include mortality, hospitalizations, reservoir, anti-drug antibodies, viral sequencing, neutralization, and acceptability.
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 26/06/2026 explanation of the sample size Experimental Group, ePGT121v1LS, 100 mg every 12 weeks., 48 weeks, 4 injections of the bNAb ePGT121v1-LS, separated 12 weeks, plus antiretroviral treatment, 38, Experimental Group, ePGT121v1LS, 100 mg every 12 weeks., 48 weeks, 4 injections of the bNAb ePGT121v1-LS, separated 12 weeks, plus antiretroviral treatment. The trial has two sequential phases. Step 1 is a non-randomized safety lead-in phase enrolling 11 infants, all of whom receive ePGT121v1-LS plus standard ART, to assess initial safety and tolerability. Step 2 is a single-blind randomized controlled phase enrolling 76 infants (38 in the intervention group and 38 in the control group) randomized 1:1 to receive either ePGT121v1-LS plus standard ART or placebo plus standard ART. The total planned sample size is 87 infants., 49,
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/06/2026 complete Primary Outcome, Safety (Serious adverse events) Proportion of participants experiencing SAEs throughout the whole trial., 48 weeks Primary Outcome, Safety (Serious adverse events) Proportion of participants experiencing SAEs throughout the whole trial., 48 weeks after randomization and first administration of IMP
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/06/2026 complete Primary Outcome, 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., 48 weeks Primary Outcome, 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., 48 weeks after randomization and first administration of IMP
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/06/2026 complete Primary Outcome, 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., 48 weeks Primary Outcome, 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., 48 weeks after randomization and first administration of IMP
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/06/2026 complete Primary Outcome, Tolerability of the treatment (participants who discontinue) • Proportion of participants who discontinue due to toxicity or tolerability issues., 48 weeks Primary Outcome, Tolerability of the treatment (participants who discontinue) • Proportion of participants who discontinue due to toxicity or tolerability issues., 48 weeks after randomization and first administration of IMP
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/06/2026 complete info Primary Outcome, Tolerability of the injection • Median score of pain assessment scale after administration of bNAb (FLACC scale)., 1 hour Primary Outcome, Tolerability of the injection • Median score of pain assessment scale after administration of bNAb (FLACC scale)., 1 hour after administration of the IMP
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/06/2026 complete Secondary Outcome, PK profile of ePGT121v1-LS Half-life, 12 weeks Secondary Outcome, PK profile of ePGT121v1-LS Half-life, 12 weeks after randomization and first administration of IMP
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/06/2026 complete Secondary Outcome, 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., 48 weeks Secondary Outcome, 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., 48 weeks after randomization and first administration of IMP
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/06/2026 Complete Secondary Outcome, 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., 48 weeks Secondary Outcome, 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., 48 weeks after randomization and first administration of IMP
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/06/2026 Complete Secondary Outcome, Acceptability The acceptability will be assessed through a series of qualitative interviews and limited quantitative assessments., 48 weeks Secondary Outcome, Acceptability The acceptability will be assessed through a series of qualitative interviews and limited quantitative assessments., 48 weeks after randomization and first administration of IMP
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/06/2026 Complete Secondary Outcome, Adverse events Number of and proportion of participants with solicited adverse event (AEs) and laboratory-related AEs., 48 weeks Secondary Outcome, Adverse events Number of and proportion of participants with solicited adverse event (AEs) and laboratory-related AEs., 48 weeks after randomization and first administration of IMP