South African National Clinical Trials Registry
South African Medical Research Council, Cochrane South Africa
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: sactradmin@mrc.ac.za Website: sanctr.samrc.ac.za
Trial no.: DOH-27-102025-4937 Date of Approval: 21/10/2025
Trial Status: Approved
TRIAL DESCRIPTION
Public title The LEN4PrEP Study: Integration of Lenacapavir PrEP within multi-method HIV prevention services: a phase 3B study
Official scientific title Integration of Lenacapavir PrEP within multi-method HIV prevention services: a phase 3B study
Brief summary describing the background and objectives of the trial Much progress has been made in the prevention of HIV with the number of people using oral PrEP globally reaching 3.5 million in 2023. However, the number of new HIV infections among adolescent girls and young women (AGYW) remains above the target of >50,000 a year. Increased access to PrEP is needed to reduce new infections, particularly among key populations and women in high HIV incidence settings. To overcome this, long-acting PrEP methods are slowly becoming available, with the Dapivirine vaginal ring (DVR) and long-acting injectable cabotegravir (CAB-LA) approved by SAHPRA and several regulatory authorities in other countries. The newest method, the twice-yearly subcutaneous injectable lenacapvir for PrEP (L4P), has been found to be safe and highly effective in preventing HIV but data around how to integrate it into existing health care systems in limited. Introducing L4P with speed and at scale requires a strategic and coordinated approach, with research, implementation science, programming and community engagement moving in parallel. However, the method uptake when L4P is offered within existing multi-method PrEP services, as well as how and when PrEP users will switch between the methods, remains unknown. This data is critical for health departments to ensure accurate demand forecasting and planning. This study will evaluate the integration of L4P within existing multi-method HIV prevention services, amongHIV-negative people in real-world settings in South Africa.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) LEN4PrEP
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Prevention
Anticipated trial start date 10/11/2025
Actual trial start date 28/11/2025
Anticipated date of last follow up 30/06/2027
Actual Last follow-up date
Anticipated target sample size (number of participants) 2000
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
LEN4PrEP Wits RHI
CO-US-974-7718 Gilead Sciences
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 Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group PrEP products available through standard of care services 1) Oral PrEP: Oral HIV pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) 1 tablet (245/200mg) daily during times of risk Participants may use each method as long as their are eligible for the trial duration (up to 12 months) Standard of care HIV prevention services that includes: o HIV and STI risk reduction counselling and the provision of condoms o Screening for GBV and mental health and management and/or referral if required o Provision of contraception according to participant’s method choice (among females of child-bearing potential) o Syndromic screening and management of STIs o Counselling on PrEP effective use o Provision of post-exposure prophylaxis as required 600 Active-Treatment of Control Group
Experimental Group Lenacapavir for PrEP At initiation: Subcutaneous (SC) L4P 927mg (2 x 1.5mL injections) administered together with a loading dose of oral lenacapavir 600 mg (2 x 300 mg tablets) once daily on the L4P initiation visit, and the day after. At follow-up visits: SC L4P 927mg (2 x 1.5mL injections) administered every 26 weeks (+/- 2 weeks). Participants that return for follow-up visit outside of the re-injection window will be treated as a reinitiation. 12 months L4P inclusive of standard of care HIV prevention services that includes: o HIV and STI risk reduction counselling and the provision of condoms o Screening for GBV and mental health and management and/or referral if required o Provision of contraception according to participant’s method choice (among females of child-bearing potential) o Syndromic screening and management of STIs o Counselling on PrEP effective use o Provision of post-exposure prophylaxis as required 1400
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Participants who meet the following criteria will be eligible for inclusion in the cohort study: 1. HIV negative confirmed through a rapid point of care antibody test conducted in accordance with the latest national HIV testing services guidelines14 2. Aged 16 years – 65 years at screening 3. Interested in HIV prevention services 4. Willing and able to provide written informed consent, or informed assent and parental consent in participants who are <18 years Participants who meet any of the following criteria will be excluded from the study: 1. Known or confirmed HIV positive through a rapid point of care antibody test conducted in accordance with the latest national HIV testing services guidelines14 2. One or more reactive or positive HIV test results at screening, even if HIV diagnosis is not confirmed 3. Currently enrolled in any interventional research study (based on self-report) Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 16 Year(s) 65 Year(s) Both
APPROVALS
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 09/09/2025 Wits HREC
Ethics Committee Address
Street address City Postal code Country
Faculty of Health Sciences, Phillip Tobias Building, Offices 301-304, 3rd Floor, Corner York Road Johannesburg 2001 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 09/10/2025 SAHPRA
Ethics Committee Address
Street address City Postal code Country
Loftus Park, Building A 402 Kirkness Street Pretoria 0083 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome L4P uptake new - The number and proportion of people who have never used PrEP before and who, after being offered multi-method prevention services (including LRP), select LRP. At enrolment
Primary Outcome L4P uptake all - The number and proportion of people who, after being offered multi-method prevention services (including L4P for the first time), select L4P. At enrolment
Secondary Outcome L4P adherence - The number and proportion of people who initiated L4P who received an ‘on-time’ injection, defined as =28 weeks from the last injection. 6 and 12 months
Secondary Outcome L4P persistence - The number and proportion of people who initiated L4P who consistently and continuously used L4P, defined as all injections being ‘on time’ (never exceeding >28 weeks between injections). 12 months
Secondary Outcome L4P continuation - The number and proportion of people who initiated L4P who are =28 weeks from their last L4P injection at a specific point in time. 12 months
Secondary Outcome L4P coverage - The number and proportion of days in a specified interval protected by L4P, defined as the number of days that were =28 weeks from the last injection. 12 months
Secondary Outcome L4P restarts - Restart events: The number and proportion of people who initiated L4P who needed to re-initiate due to exceeding >28 weeks between injections. Time to Restart: The time (mean, median) between injections among individuals initiating L4P who needed to re-initiate L4P. 6 and 12 months
Secondary Outcome L4P switchers - The number and proportion of people who have previously used PrEP, (after being offered multi-method prevention services including L4P), who select a PrEP method different to the method previously used 6 and 12 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Province Country
Wits RHI 22 Esselen Street, Hillbrow Johannesburg South Africa
FUNDING SOURCES
Name of source Street address City Province Country
UNITAID 1218 Grand-Saconnex Geneva Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Wits Health Consortium 31 Princess of Wales Terrace Johannesburg South Africa Research Institute
COLLABORATORS
Name Street address City Province Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Saiqa Mullick smullick@wrhi.ac.za +27113585300 22 Esselen Street, Hillbrow
City Postal code Country Position/Affiliation
Johannesburg South Africa Director
Role Name Email Phone Street address
Scientific Enquiries Catherine Martin cmartin@wrhi.ac.za +27113585300 22 Esselen Street, Hillbrow
City Postal code Country Position/Affiliation
Johannesburg South Africa Senior Technical Specialist
Role Name Email Phone Street address
Public Enquiries Vusile Butler vbutler@wrhi.ac.za +27113585300 22 Esselen Street, Hillbrow
City Postal code Country Position/Affiliation
Johannesburg South Africa Technical Head Programme Implementation
Role Name Email Phone Street address
Scientific Enquiries Roisin Drysdale rdrysdale@wrhi.ac.za +27113585300 22 Esselen Street, Hillbrow
City Postal code Country Position/Affiliation
Johannesburg South Africa Senior Researcher
Role Name Email Phone Street address
Principal Investigator Mrinmayee Dhar mdhar@wrhi.ac.za +27113585300 22 Esselen Street, Hillbrow
City Postal code Country Position/Affiliation
Johannesburg South Africa Research Clinician
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Anonymized individual participant data Informed Consent Form,Study Protocol The IPD data will be shared in accordance with Wits RHI Data Access Policy or Data Management Plan, whichever comes first. The IPD data and additional documents will be available for sharing 2 years after completion of the study unless otherwise specified in the study data management plan. Access to the IPD and the associated documents will require completion of a data access application form. Data users will be required to abide by the data use conditions stipulated on the application for access to the data.
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 Public title 14/10/2025 Request from reviewers The LEN4PrEP Study The LEN4PrEP Study: Integration of Lenacapavir PrEP within multi-method HIV prevention services: a phase 3B implementation study
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Public title 24/11/2025 Removal of the word integration in the study title to align with the approved SAHPRA title. The LEN4PrEP Study: Integration of Lenacapavir PrEP within multi-method HIV prevention services: a phase 3B implementation study The LEN4PrEP Study: Integration of Lenacapavir PrEP within multi-method HIV prevention services: a phase 3B study
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Official scientific title 24/11/2025 Removal of the word integration in the study title to align with the approved SAHPRA title. Integration of Lenacapavir PrEP within multi-method HIV prevention services: a phase 3B implementation study Integration of Lenacapavir PrEP within multi-method HIV prevention services: a phase 3B study
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 14/01/2026 To reflect actual trial start date 28 Nov 2025
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 14/01/2026 To reflect anticipated last follow-up date based on actual trial start date 31 Mar 2027 30 Jun 2027
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 14/01/2026 To reflect current status Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 14/10/2025 Request from reviews to align site with ethics approvals Wits RHI , 22 Esselen Street, Hillbrow , Johannesburg , , South Africa
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 14/10/2025 Please note, the only letter received from the ethics committee is the approval certificate attached. True, Wits HREC , Faculty of Health Sciences, Phillip Tobias Building, Offices 301-304, 3rd Floor, Corner York Road, Johannesburg, 2001, South Africa, , 11 Sep 2025, 0117172700, ethicsregulatory@witshealth.co.za, 13831_22300_4737.pdf, 250610 True, Wits HREC , Faculty of Health Sciences, Phillip Tobias Building, Offices 301-304, 3rd Floor, Corner York Road, Johannesburg, 2001, South Africa, , 11 Sep 2025, 0117172700, ethicsregulatory@witshealth.co.za, 13831_22300_4737.pdf, 250610
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 17/10/2025 Request from reviewers True, Wits HREC , Faculty of Health Sciences, Phillip Tobias Building, Offices 301-304, 3rd Floor, Corner York Road, Johannesburg, 2001, South Africa, , 11 Sep 2025, 0117172700, ethicsregulatory@witshealth.co.za, 13831_22300_4737.pdf, 250610 True, Wits HREC , Faculty of Health Sciences, Phillip Tobias Building, Offices 301-304, 3rd Floor, Corner York Road, Johannesburg, 2001, South Africa, , 09 Sep 2025, 0117172700, ethicsregulatory@witshealth.co.za, 13831_22300_4737.pdf, 250610