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 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202302484199604 Date of Approval: 08/02/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Long-Acting Treatment in Adolescents (LATA)
Official scientific title Long-Acting Treatment in Adolescents (LATA): A randomised open-label 2-arm 96 week trial in virologically suppressed HIV-1-positive adolescents aged 12-19 years of age in Sub-Saharan Africa
Brief summary describing the background and objectives of the trial Background: Over 2 million adolescents aged 10-19 years are living with HIV, the majority in sub-Saharan Africa (SSA). Current treatment recommendations are to take life-long, daily oral antiretroviral therapy (ART). While this is very successful in older people, the same is not true for adolescents and young people, who have much higher rates of dropping out of healthcare, and higher mortality from HIV. In SSA, it is clear that there is a need for novel ART strategies to improve quality-of-life, engagement in care and treatment adherence for the large numbers of HIV-positive children who were infected at birth who are now entering adolescence, and for adolescents newly-infected through sexual transmission. Objectives of the Study: There is now a new way of taking HIV medicines in the form of two injections called long-acting injectables, which must be given every 8 weeks in the clinic. In LATA, we will investigate whether taking these long-acting injectable medicines works just as well as taking oral HIV medicines every day for young HIV-positive people aged 12-19 years. We need 460 young people living with HIV-1 from Kenya, South Africa, Uganda and Zimbabwe to be part of the LATA trial. Participants will be randomised, with an equal chance that they will either go into the long-acting injectable group or get a daily ART tablet by mouth. The two randomised groups are: • Long-Acting (LA) Injectable Group: In this group, long-acting injectables called cabotegravir (CAB) and rilpivirine (RPV) will be given every 8 weeks for at least 96 weeks. • Continuous Therapy (CT) Control Group: this group will continue to take their HIV medicines every day by mouth. To join the trial, some participants might have to change some of their oral medications, as the combination being used in LATA is TLD. TLD is dolutegravir and tenofovir, plus either lamivudine or emtricitabine, as a single tablet taken once a day.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) LATA
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Drugs
Anticipated trial start date 30/03/2023
Actual trial start date 22/06/2023
Anticipated date of last follow up 30/03/2025
Actual Last follow-up date 22/04/2024
Anticipated target sample size (number of participants) 460
Actual target sample size (number of participants) 476
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
NCT05154747 Clinicaltrials.gov
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 Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Combination oral ART Until the end of study Dolutegravir 50mg oral with tenofovir disoproxil fumarate (245mg) and lamivudine (300mg) in a fixed dose combination or Dolutegravir 50mg oral with tenofovir alafenamide fumarate (25mg) and lamivudine (300mg) (l/TAF) oral in a fixed dose combination 230 Active-Treatment of Control Group
Experimental Group Long Acting Injectable Cabotegravir and Rilpivirine Cabotegravir Long-Acting (LA) 600mg as a 3mL intramuscular (IM) injection and rilpivirine LA 900mg as a 3mL IM injection. Cabotegravir LA will be given IM into one buttock, and rilpivirine LA will be given IM into the opposite buttock. First loading doses of CAB/RPV LA given at the week 4 visit and the second loading doses at week 8.The maintenance doses of CAB/RPV LA given every 8 weeks, starting at the week 16 visit. Until the end of study Cabotegravir LA 600mg as a 3mL IM injection. The product is packaged in a 3mL USP Type I glass vial. Each vial is for single-dose use. CAB LA injectable suspension is to be stored according to the product label at room temperature (<30oC). CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol3350, mannitol, and water for injection. Rilpivirine LA 900mg as a 3mL IM injection. Each single-dose vial contains 900mg/3mL rilpivirine. RPV LA injectable suspension should be stored according to the product label refrigerated at 2-8oC and should be protected from light. RPV LA is composed of RPV free base, poloxamer 338, sodium dihydrogen phosphate monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, and water for injection. 230
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. HIV-1-positive 2. Aged 12-19 years 3. Aware of HIV status 4. Body weight ≥35Kg 5. On ART consisting of 2NRTI and a third agent 6. On ART for ≥1 year with no previous regimen change for treatment failure* 7. Virologically suppressed with all HIV-1 RNA viral loads <50copies/mL¥ in the last 12 months up to and including screening. Additionally, there must be one result <50copies/mL¥ at least 12 months prior to screening and the viral load at trial screening must be <50 copies/mL 8. Written informed consent provided by participant (if aged 18 to 19 years) and/or carer/legal guardian (if participant aged 12 to 17 years) as appropriate 9. Written informed assent in participants aged 12 to 17 years 10. Females who are sexually active must be willing to adhere to highly effective methods of contraception⌂ * Treatment failure includes virological, immunological or clinical failure where regimen has been changed for lack of response to treatment ¥ The screening sample VL must be <50 copies/mL. For samples prior to screening, a diluted sample may be used; if the viral load in the diluted sample is below lower limit of quantification (LLQ), a calculated VL<100 copies/mL is allowed; if the viral load in the diluted sample is equal or above LLQ the calculated VL should be below 50 copies/mL. ⌂ Highly effective contraception are injectable, implantable, oral and intrauterine contraceptives which have an expected failure rate <1% per year; in the LA group, must avoid pregnancy for 12 months after the last dose of the CAB and RPV LA 1. Known HIV-2 positive 2. Females who are pregnant or breastfeeding 3. Females who plan to become pregnant during the trial follow-up or are sexually active and are unwilling to avoid pregnancy for the duration of the trial 4. Moderate or high-risk score on the Columbia-Suicide Severity Rating Scale 5. Hepatitis B SAg positive 6. ALT ≥3 x upper limit of normal 7. On treatment for active TB 8. Known contraindication to receipt of dolutegravir, cabotegravir, rilpivirine, emtricitabine/ lamivudine and any formulation of tenofovir 9. Participants determined by the investigator to have a high risk of seizure, including those with unstable or poorly controlled seizure disorder 10. Unwilling or contraindication to receiving injections 11. Contraindication to receiving injectable agents in the buttock area 12. Underlying medical condition (e.g. bleeding disorder; use of warfarin) that in the opinion of the investigator precludes participation 13. Previous randomisation in the BREATHER Plus trial 14. Known major** resistance to non-nucleoside reverse transcriptase inhibitors or integrase inhibitors **Major NNRTI and INSTI mutations are those listed in the IAS report (www.iasusa.org/resources/hiv-drug-resistance-mutations/ - which is likely to change over time (36) Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Child: 6 Year-12 Year 12 Year(s) 19 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
Yes 22/02/2022 University College London
Ethics Committee Address
Street address City Postal code Country
2 Taviton Street London WC1H 0BT United Kingdom
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 18/10/2022 Pharma Ethics
Ethics Committee Address
Street address City Postal code Country
123 Amkor Road, Lyttelton Manor Ext 3, Centurion Gauteng 786 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 26/08/2022 Joint Clinical Research Centre Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Plot 101 Lubowa Estates, Off Entebbe Road Kampala 10005 Uganda
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 03/10/2022 Joint Research Ethics Committee for The University of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
JREC Office No.4, 5th Floor, Faculty of Medicine and Health Sciences Building Harare Box A178 Zimbabwe
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 16/02/2023 Institutional Research and Ethics Committee IREC
Ethics Committee Address
Street address City Postal code Country
Moi University College of Health Sciences Eldoret PO Box 46 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The proportion of participants with confirmed virological rebound, defined as 2 consecutive plasma HIV-RNA ≥50 copies/mL at any time up to the 96 week assessment 48 and 96 weeks
Secondary Outcome Proportions of participants with HIV-RNA ≥50 copies/mL at 48 and 96 weeks using a modified FDA snapshot algorithm 48 and 96 weeks
Secondary Outcome The proportion of participants with HIV-RNA ≥1000 copies/mL (confirmed) by week 96 Up to week 96 assessment
Secondary Outcome The proportion of participants with HIV-RNA ≥200 copies/mL (confirmed) by week 96 Up to week 96 assessment
Secondary Outcome The number and type of HIV mutations (reverse transcriptase and integrase) in participants with confirmed virological rebound Up to week 96 assessment
Secondary Outcome HIV-RNA <50 copies/mL at 24, 48 and 96 weeks 24, 48 and 96 weeks
Secondary Outcome Change in metabolic parameters (lipids, HbA1c, phosphate), liver function tests (ALT), renal function (eGFR) from baseline to 96 weeks; change in anthropometric measures, including weight, from baseline to 48 and 96 weeks 48 and 96 weeks
Secondary Outcome Time to any new or recurrent WHO grade 3 or WHO grade 4 event or death To end of trial follow-up
Secondary Outcome Incidence of serious, grade 3, 4 and 5, and treatment-modifying (of any grade) adverse events To end of trial follow-up
Secondary Outcome The proportion of participants with any change from baseline ART regimen To end of trial follow-up
Secondary Outcome Change in CD4+ and CD8+ T-cell count from baseline to 48 and 96 weeks 48 and 96 weeks
Secondary Outcome LA group only: incidence of injection-site reactions of any grade To end of trial follow-up
Secondary Outcome Adherence, acceptability, wellbeing and neuropsychiatric problems (e.g. depression, anxiety and sleep disturbance) To end of trial follow-up
Secondary Outcome LA group only: perception of injection To end of trial follow-up
Secondary Outcome Healthcare resource utilisation (as a sub-study outcome) To end of trial follow-up
Secondary Outcome Health-related quality-of-life (as a sub-study outcome) To end of trial follow-up
Secondary Outcome Perception of body shape using Stunkard figure rating scales (as a sub-study outcome) To end of trial follow-up
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Baylor College Block 5 Mulago Hospital Kampala Uganda
Joint Clinical Research Centre Plot 101 Lubowa Estates, off Entebbe road Kampala Uganda
University of Zimbabwe Clinical Research Centre 1578 Avondale Harare Zimbabwe
Moi University Nandi Road Eldoret Kenya
Durban International Clinical Research Site Enhancing Care Foundation Parkhome, King Edward VIII Hospital, Umbilo Road, Congella Durban South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP 2509 AA The Hague Netherlands
Janssen Cilag Ltd Turnhoutseweg 30 Beerse 2340 Belgium
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University College London Gower Street London United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Baylor College Block 5 Mulago Hospital Kampala Uganda
Joint Clinical Research Centre Plot 101 Lubowa Estates, off Entebbe road Kampala Uganda
University of Zimbabwe Mazowe Street Harare Zimbabwe
Moi University Nandi Road Eldoret Kenya
Radboud University Medical Center 6525 EZ Nijmegen The Hague Netherlands
London School of Hygiene and Tropical Medicine Keppel Street London United Kingdom
University of York Heslington York United Kingdom
Enhancing Care Foundation NPC 16 Charles Strachan Road Durban South Africa
Fondazione PENTA ONLUS Corso Stati Uniti 4 Padova Italy
Uganda Virus Research Institute Plot 51-59 Nakiwogo Road Entebbe Uganda
Africa Health Research Institute 719 Umbilo Road Durban South Africa
University College London Gower Street London United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Sarah Pett s.pett@ucl.ac.uk +442076704785 90 High Holborn
City Postal code Country Position/Affiliation
London WC1V 6LJ United Kingdom LATA Chief Investigator and Project Lead
Role Name Email Phone Street address
Public Enquiries Molly Bush molly.bush@ucl.ac.uk +442076704641 90 High Holborn
City Postal code Country Position/Affiliation
London WC1B 6LJ United Kingdom Trial Manager
Role Name Email Phone Street address
Scientific Enquiries Sarah Pett s.pett@ucl.ac.uk +442076704785 90 High Holborn
City Postal code Country Position/Affiliation
London WC1V 6LJ United Kingdom LATA Chief Investigator and Project Lead
Role Name Email Phone Street address
Principal Investigator Adeodata Kekitiinwa Rukyalekere akekitiinwa@baylor-uganda.org +256772462686 Baylor College of Medicine Childrens Foundation Uganda
City Postal code Country Position/Affiliation
Kampala Uganda Country Principal Investigator
Role Name Email Phone Street address
Principal Investigator Moherndran Archary archary@ukzn.ac.za +270312604813 Enhancing Care Foundation King Edward VIII Hospital
City Postal code Country Position/Affiliation
Durban South Africa Country Principal Investigator
Role Name Email Phone Street address
Principal Investigator Mutsa Bwakura Dangarembizi dangas@zol.co.zw +2634705986 University of Zimbabwe Clinical Research Centre
City Postal code Country Position/Affiliation
Harare Zimbabwe Country Principal Investigator
Role Name Email Phone Street address
Principal Investigator Abraham Siika amsiika@africaonline.co.ke +254721280785 Moi University
City Postal code Country Position/Affiliation
Eldoret Kenya Country Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data collected in the study will be available for additional research with justified scientific objectives. LATA will follow a controlled access approach to making data available outside of the trial whereby researchers make formal applications for data sharing. Where a proposal has been approved, the required Individual Participant Data (IPD) will be shared with the researchers on the Data Sharing Agreement to meet the requirements of the proposal. Proposals should be sent to mrcctu.lata@ucl.ac.uk. Further information on criteria and application can be found on the MRC CTU webpage on data sharing at the following link https://www.mrcctu.ucl.ac.uk/our-research/other-research-policy/data-sharing/. Clinical Study Report,Statistical Analysis Plan,Study Protocol Data will be made available as per agreed timelines following approval of a data sharing request (which is unlikely to be approved before the primary trial publication). There is a controlled access approach whereby access to trial data can be requested by qualified researchers engaging in independent scientific research. As per the MRC CTU at UCL’s Data Sharing and Data Reuse SOP, access will be provided following a formal application detailing the specific requirements, proposed research, qualification of researchers and publication plan, and execution of a Data Sharing Agreement. For more information or to submit a request, please contact mrcctu.lata@ucl.ac.uk.
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