Long-Acting Treatment in Adolescents (LATA)

NCT05154747 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 129628
• Study Type: interventional
• Target: 476
• Locations: 4 countries
• Sites: 5

Brief Summary

The LATA trial will find out if taking a long-acting injectable form of HIV medicines, called cabotegravir and rilpivirine, every 2 month works as well as taking tablet HIV medicines every day in young people aged 12-19 years of age. The trial is organised by an international group of researchers from Europe and Africa, and will include 460 young people, from Kenya, South Africa, Uganda and Zimbabwe.

Conditions

Hiv; HIV Infections; HIV-1-infection; Paediatric Human Immunodeficiency Virus Infection

Outcome Measures

Primary Outcomes (1)

• Confirmed virological rebound

  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

  Up to 96 week assessment

Secondary Outcomes (20)

• Efficacy Outcome: Proportions of participants with HIV-RNA ≥50 copies/mL

  At week 48 and week 96 visits

• Efficacy Outcome: The proportion of participants with confirmed HIV-RNA ≥1000 copies/mL

  Up to week 96 assessment

• Efficacy Outcome: The proportion of participants with confirmed HIV-RNA ≥200 copies/mL

  Up to week 96 assessment

• Efficacy Outcome: The number of HIV reverse transcriptase mutations

  Up to week 96 assessment

• Efficacy Outcome: The number of HIV integrase mutations

  Up to week 96 assessment

Other Outcomes (9)

• Patient-Reported Outcome: Adherence to trial medications questionnaire

  From baseline to 96 weeks

• Patient-Reported Outcome: Acceptability and Wellbeing

  From baseline to 96 weeks

• Patient-Reported Outcome: Depression

  From baseline to 96 weeks

Study Arms (2)

Continuous Therapy (CT) Control Group

ACTIVE COMPARATOR

The control group is a continuous daily oral combination ART consisting of dolutegravir (DTG), with a tenofovir (TFV) and lamivudine(3TC)/emtricitabine(FTC) backbone

Drug: TLD

Long Acting (LA) Injectable Group

EXPERIMENTAL

The intervention group is a long-acting injectable, cabotegravir (CAB) LA and rilpivirine (RPV) LA given every 8-weeks after an optional 4-week oral lead-in period with oral cabotegravir and rilpivirine, and two loading doses separated by 4 weeks.

Drug: Cabotegravir, Rilpivirine Drug Combination

Interventions

Cabotegravir, Rilpivirine Drug Combination DRUG

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. Cabotegravir Long-Acting (CAB LA) will be given IM into one buttock, and Rilpivirine Long-Acting (RPV LA) will be given IM into the opposite buttock.

Also known as: CAB, RPV

Long Acting (LA) Injectable Group

TLD DRUG

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

Continuous Therapy (CT) Control Group

Eligibility Criteria

• Age: 12 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• HIV-1-infected
• Aged 12-19 years
• Aware of HIV status
• Body weight ≥35Kg
• On ART consisting of 2NRTI and a third agent
• On ART for ≥1 year with no previous regimen change for treatment failure\*
• 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
• 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
• Written informed assent in participants aged 12 to 17 years
• 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

You may not qualify if:

• Known HIV-2 infection
• Females who are pregnant or breastfeeding
• 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
• Moderate or high-risk score on the Columbia-Suicide Severity Rating Scale
• Hepatitis B SAg positive
• ALT ≥3 x upper limit of normal
• On treatment for active TB
• Known contraindication to receipt of dolutegravir, cabotegravir, rilpivirine, emtricitabine/ lamivudine and any formulation of tenofovir
• Participants determined by the investigator to have a high risk of seizure, including those with unstable or poorly controlled seizure disorder
• Unwilling or contraindication to receiving injections
• Contraindication to receiving injectable agents in the buttock area
• Underlying medical condition (e.g. bleeding disorder; use of warfarin) that in the opinion of the investigator precludes participation
• Previous randomisation in the BREATHER Plus trial
• 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

Sponsors & Collaborators

• University College, London: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• Janssen-Cilag Ltd.: collaborator
• ViiV Healthcare: collaborator
• Department of Clinical Pharmacy, University Medical Centre St Radboud, The Netherlands.: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• MRC/UVRI and LSHTM Uganda Research Unit: collaborator
• Africa Health Research Institute: collaborator
• PENTA Foundation: collaborator
• University of York: collaborator

Study Sites (5)

Moi University

Eldoret, Kenya

Location

Enhancing Care Foundation King Edward VIII Hospital

Durban, South Africa

Location

Baylor College of Medicine Childrens Foundation Uganda

Kampala, Uganda

Location

Joint Clinical Research Centre

Kampala, Uganda

Location

University of Zimbabwe Clinical Research Centre

Harare, Zimbabwe

Location

Related Publications (1)

• Anena D, Chappell E, Nazzinda R, Kiilu C, Chitsamatanga M, Arumugam T, Green A, Mutuluuza CK, Bwakura-Dangarembizi M, Siika A, Archary M, Jafta L, Namukwaya S, Seeley J, Akabwai G, Mugerwa H, Bevers L, Burger D, Walker S, Bamford A, South A, Apoto N, Bush M, Thomason MJ, Spittle B, Ford D, Kekitiinwa AR, Pett SL; LATA Trial Team. Trial design and enrolment characteristics of LATA (long-acting treatment in adolescents): A randomised, open-label, non-inferiority, 96-week trial evaluating the virological efficacy, safety, acceptability and quality-of-life of the dual long-acting injectable regimen cabotegravir/ rilpivirine compared to daily oral therapy in virologically suppressed adolescents with HIV-1 infection, aged 12 to <20 years, in Sub-Saharan Africa. Contemp Clin Trials. 2026 Jan 7:108213. doi: 10.1016/j.cct.2025.108213. Online ahead of print.

  PMID: 41512916 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

cabotegravir, rilpivirine drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Sarah L Pett

  MRC CTU at University College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2021
• First Posted: December 13, 2021
• Study Start: June 22, 2023
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2026
• Last Updated: April 29, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: 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).
• Access Criteria: 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.

Locations

ZI (1); ZA (1); UG (2); KE (1)