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.: PACTR202402700796695 Date of Approval: 01/02/2024
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Acceptability and Feasibility of long-acting INjectable ART in Adolescents and Young Adults.
Official scientific title Acceptability and Feasibility of long-acting INjectable ART in Adolescents and Young Adults.
Brief summary describing the background and objectives of the trial South Africa has the largest population of people living with HIV (PLWH), with young people being disproportionately affected. A systematic review of the literature indicated that 15-24 year olds in South Africa have strong intentions to enter care but it was estimated that only 14% started treatment and only 10% of this population is virally suppressed. Long-acting injectable (LAI) antiretroviral therapy (ART) in the form of a cabotegravir and rilpivirine combination has been demonstrated in multiple studies to be non-inferior to current daily oral regimens in adult populations at both 4-and 8-weekly dosing intervals. Furthermore, these studies showed low drug-related discontinuation and high acceptability and satisfaction in this population4. Currently, the MOCHA study is underway in young people aged 12-18 years who are virally suppressed, with an estimated primary completion date in late 20225. Successful implementation of novel LAI interventions will require implementation studies to understand end users attitudes as well as explore scalable delivery strategies. The effectiveness, acceptability and feasibility of LAI treatment for young people in low resource areas are currently unknown. This implementation science cohort study investigates the acceptability of cabotegravir LA + rilpivirine LA (CAB LA + RPV LA) in 200 young people (ages 12-24), including subgroups of ART-naïve young people and those with prior virologic breakthrough.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) AFINAty
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 03/10/2022
Actual trial start date 12/12/2022
Anticipated date of last follow up 19/12/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 200
Actual target sample size (number of participants) 170
Recruitment status Closed to recruitment,follow-up continuing
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 Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Cohort 1 Young people on long term standard of care ART with viral suppression IM CAB LA 600mg and RPV LA 900mg 48 weeks Approximately 75 adolescents and young people on long term standard of care, first-line ART, with excellent adherence, evidenced by viral suppression for more than 1 year (last 2 standard of care viral loads <50 copies/ml, most recent within the past 12 months). After meeting eligibility criteria, they will be offered optional oral CAB and RPV lead-in for one month, followed by 6 intramuscular injections (IM) of CAB LA 600mg and RPV LA 900mg (dosing at weeks 4, 8, 16, 24, 32 and 40). At week 48 they will be offered the option of switching back to their SOC ART or continuing with LAI through post-trial access. 75 Active-Treatment of Control Group
Experimental Group Cohort 2 Young people on ART with evidence of poor adherence. IM CAB LA 600mg and RPV LA 900mg 48 weeks Approximately 50 adolescents and young people taking long term oral SOC first-line ART, but with evidence of recent poor adherence (within the past 12 months): either the most recent viral load >50 copies/ml, or a missed collection of medication from the pharmacy in the past year. After meeting eligibility criteria, this cohort will receive enhanced adherence support while continuing their oral SOC ART, from week -24 to week 0, including data-driven counselling sessions with a clinician and 4 peer group sessions managed by an experienced lay counsellor). A viral load will be repeated at -12 weeks and week 0 and if suppressed (<50 copies/ml) at either visit, the participant will be offered optional oral CAB and RPV lead-in for one month at week 0, followed by 6 injections of IM CAB LA 600mg and RPV LA 900mg (dosing at weeks 4, 8, 16, 24, 32 and 40). At week 48 they will be offered the option of switching back to their SOC ART or continuing with LAI through post-trial access. 50
Experimental Group Cohort 3 Young people with HIV who are ART naive. IM CAB LA 600mg and RPV LA 900mg 48 weeks Approximately 75 of adolescents and young people who are ART-naïve. After meeting eligibility criteria, this cohort will commence oral SOC first-line ART at week -24. A viral load will be repeated at week -12 and week 0 and if suppressed (<50 copies/ml) at either visit, the participant will be offered optional oral CAB and RPV lead-in for one month, followed by 6 IM injections of CAB LA 600mg and RPV LA 900mg (dosing at weeks 4, 8, 16, 24, 32 and 40). At week 48 they will be offered the option of switching back to their SOC ART or continuing with LAI through post-trial access 75
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Known HIV-1 positive. • Aged 12 - 24 years inclusive. • Clinically well (no current HIV-related illnesses). • Weight ≥ 35 kg. • Willing to switch to a long-acting injectable ART regimen for a 48-week period. • Be virally suppressed (<50 copies/ml) at time of switch. • Willing to be followed by the study team for 96 weeks after switch. • Able to understand and comply with protocol requirements and sign full informed assent / consent. • For women and adolescents of childbearing potential, be willing to use effective contraception for the duration of the study (including the post-trial access period and the 48-week follow-up phase). This includes the use of oral or injectable hormonal contraceptives, a contraceptive implant or an intrauterine device (IUD). In addition, for cohort 1 (n=75): • Currently receiving standard of care first-line ART. • Suppressed viral load at the last 2 SOC measurements, with the most recent viral load drawn within 12 months of screening date (so indicating >1 year of viral suppression). Note: SOC viral load are drawn every 12 months. • No evidence of recent poor adherence (e.g. missed clinic visits or missed pharmacy collection). In addition, for cohort 2 (n=50): • Currently receiving standard of care first-line ART. • Most recent clinic viral load ≥50 copies/ml (but previous viral load suppressed) OR other evidence of poor adherence in past year (e.g. a missed pharmacy collection or missed clinic visits). • Willing to receive enhanced adherence support prior to switch. In addition, for cohort 3 (n=75) • ART-naïve, by self-report. • About to commence SOC first-line ART; • Adolescent or caregiver unwilling to participate in an ART switch study. • History of hypersensitivity to any of the study drugs or their components. • Known HIV-1 resistance to any of the study ART drug groups (NNRTIs or INSTIs). • History of seizures or people at risk of seizures. • Abnormal liver function (>2.5 x ULN ALT or AST). • Evidence of Hepatitis B infection (positive Hep B surface antigen or anti-core AB). • Severe hepatic impairment and those with advanced hepatitis C, or those expected to need the introduction of new treatment for hepatitis C during the course of the study. • People who are at high risk of suicide. • Women who are pregnant or breastfeeding. • Participant is acutely ill with COVID-19 infection. • Use of prohibited medication (e.g. rifampicin). • Coagulopathy or use of anticoagulants which would preclude IM injections. • Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the Investigator, may interfere with the participant’s ability to comply with the dosing schedule or which may compromise the safety of the participant. Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year 12 Year(s) 24 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 13/10/2022 University of Cape Town Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
E53-46, Old Main Building, Groote Schuur Hospital, Mowbray. Cape Town. 7925 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Acceptability and tolerability of injectable method of ART delivery by adolescents (drawn from adverse event data as well as qualitative data from IDIs). Week 48
Primary Outcome Feasibility of delivering injectable ART in a community setting (drawn from adherence to injection schedule by each cohort, and from key informant interviews). Weeks 0 to 48
Primary Outcome Adherence to study visits and to injectable product over the study period Weeks 0 to 48
Secondary Outcome Efficacy of long-acting injection regimen in each cohort (drawn from rate of ongoing viral suppression at end of injection period) Weeks 24 and 48
Secondary Outcome To assess viral resistance in participants experiencing Viral load ≥ 50 copies/ml at any visit beyond week 0 (explored at any raised viral load, not only if meets viral failure criteria). Weeks 0 to 48
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre for Adherence and Therapeutics at the Desmond Tutu Health Centre Scout Hall, Masibambane Street, Gugulethu Capw Town 7806 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Johnson and Johnson Turnhoutseweg 30 Beerse Belgium
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Desmond Tutu Health Foundation 3 Woodlands Rd Cape Town 7925 South Africa Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Catherine Orrell catherine.orrell@hiv-research.org.za +834561969 3 Woodlands Rd
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa PI
Role Name Email Phone Street address
Public Enquiries Nyiko Mashele nyiko.maashele@hiv-research.org.za +762454500 3 Woodlands Rd
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Project Manager
Role Name Email Phone Street address
Scientific Enquiries Lauren Jennings lauren.jennings@hiv-research.org.za +27827708368 3 Woodlands Rd
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Each participant will receive a unique participant identification number, which will be used for identification for the duration of the study on all source, case report forms (CRFs) and transcript documents, with the exception of the locator information form that contains their address and contact information, which will be kept separately in a locked cupboard at the research office. Data will be collected for this study on an open access electronic data capture system using a password protected platform, with a limited number of paper-based documents. The study visit case record form will be completed as soon as possible after the study visit. The principal investigators have overall responsibility for ensuring the data collected are complete, accurate, and recorded in a timely manner. Confidentiality of records will be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirements. Once the electronic case report form (eCRF) is completed data staff will monitor the data for completeness and accuracy. Any discrepancies, either manual or automatic, will be corrected by site staff. Corrections to eCRFs will only be possible by study personnel with sufficient authorisation to make changes. All changes will have an electronic date stamp. Corrections to paper-based forms can only be done by study staff and must be signed and dated. All hard copies of source and CRF’s documents will be kept in a locked cupboard at the research office or secure long-term storage facility for ten years. Electronic data will be stored in a password-protected folder on the secure company server. At the end of the study de-identified data will be available from the principal investigator on request. Informed Consent Form,Study Protocol Within 12 months of last patient reaching week 48. At the end of the study de-identified data will be available from the principal investigator on 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