Impact of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis persistence and coverage in men who have sex with men in France: a randomized controlled clinical trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Inserm

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Health Care [N] - Health Care Quality, Access, and Evaluation [N05]

Trial duration

14 May 2025 → ongoing

Decision date (initial)

2024-09-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Inserm-ANRS MIE · ViiV Healthcare

External identifiers

EU CT number

2024-510678-25-00

ClinicalTrials.gov

NCT06273943

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Efficacy

To compare the sustained PrEP use over time among participants randomized to cabotegravir vs. oral TDF/FTC based PrEP at Month 12.

Secondary objectives 22

1. To compare the sustained PrEP use over time among participants receiving cabotegravir vs. oral TDF/FTC-based PrEP at Month 24.
2. To describe the cause of non-sustained PrEP use over time at Month 12 and 24.
3. To compare the PrEP coverage of the last reported condomless anal sexual intercourse before study visits at Month 12 and 24.
4. To compare the change from baseline of the participant’s satisfaction regarding their PrEP regimen at Month 12 and 24
5. To compare the change from baseline in sexual risk behaviors at Month 12 and 24.
6. To compare the incidence of sexually transmitted infections at Month 12 and 24
7. To compare the change from baseline in weight, blood pressure, fasting lipid level and HOMA index at Month 12 and 24
8. To evaluate the safety of the drug in each study group at Month 12 and 24
9. To evaluate the injections sites reactions among participants receiving CAB-LA at Month 12 and 24
10. To evaluate the fidelity to study visits in each study group at Month 12 and 24
11. To evaluate the proportion of participants who switch their PrEP regimen within each study group (TDF/FTC: daily ⇆ on-demand, CAB: CAB oral ⇆ CAB-LA) at Month 12 and 24
12. To evaluate the time covered by a PrEP prescription in each study group at Month 12 and 24
13. To measure the drug concentrations in each study group at Month 12 and 24
14. To evaluate HIV incidence within each study group at Month 12 and 24
15. To describe antiretroviral drug resistance in participants who acquired HIV during the study at Month 12 and 24
16. To evaluate the use of psychoactive substances within each study group.
17. To evaluate the quality of life and mental health within each study group
18. To evaluate PrEP perceptions and knowledge within each study group.
19. To evaluate the use of community peer support and patient therapeutic education in each group.
20. Ancillary study – Qualitative study of the Social Science component : - In the TDF/FTC group, two focus group will be done with 5-10 participants in the months following randomization. The aim is to gather their opinions and perceptions of injectable PrEP. - In the CAB-LA group, repeated focus groups will be done in the months following randomization and 12- months after with three groups of 5-10 participants. The aim is to investigate their perceptions of CABLA, motivations for using it, adherence and persistence, changes in HIV risk perception, impact on sexual satisfaction, and experiences with healthcare providers. - Among healthcare providers, perceptions, barriers and facilitators concerning CAB-LA implementation for PrEP will be evaluated using individual semi-structured interviews with two populations, those who are have experience with long acting injectable antiretroviral therapy and those who do not (10-15 participants).
21. Ancillary study – Rectal tissue HIV-1 permissibility: - To evaluate the CAB concentration in plasma, rectal secretions, and rectal biopsies at different time points after CAB initiation for the two CAB regimen (oral and injectable). - To correlate the Ex-vivo rectal tissue infection results to the cabotegravir concentration in plasma and rectal tissue for the two CAB regimen (oral and injectable). - To compare the mean HIV reduction risk at the rectal mucosal level between TDF/FTC and each of the two CAB-based PrEP regimen at different time points. - To compare the proportion of infected explants between TDF/FTC and each of the 2 CAB-based PrEP regimen at different time points. - To evaluate the protection at different time points after TDF-FTC based PrEP initiation. - To correlate the Ex-vivo rectal tissue infection results to the tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentration in PBMCs and rectal tissue.
22. Ancillary study – Medico-economics analysis: The main objective is to establish cost-effectiveness performance benchmarks for CAB-LA in HIV PrEP. The specific objectives are to: - To develop a decision model to compare the two PrEP strategies, standard oral TDF/FTC-based PrEP and CAB-LA for PrEP users; - To estimate health utility associated to the health-related quality of life for both strategies; - To estimate lifetime risk of HIV infection, HIV healthcare cost, life expectancy, and quality-adjusted life expectancy (QALY).

Conditions and MedDRA coding

HIV prevention

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥ 18 years.
2. Cisgender men who have sex with men.
3. Have taken oral TDF/FTC based PrEP during the past 6 months, either daily or on-demand, with a documented PrEP prescription.
4. Person affiliated with or a beneficiary of a social security scheme (article L1121-11 of the Public Health Code).
5. Informed and written consent, signed by the person and the investigator on the day of inclusion, at the latest, and before any examination carried out within the setting of the study (article L1122-1-1 of the Public Health Code).

Exclusion criteria 21

1. - Positive HIV test result at screening or enrollment visit, even if HIV infection is not confirmed.
2. - Symptoms and/or clinical signs consistent with an acute HIV infection.
3. - History of seizure disorder.
4. - Ongoing Post-Exposure Prophylaxis (PEP) for HIV.
5. - Last titer of hepatitis B surface antibody (anti-HBs) < 10 mIU/mL.
6. - Concomitant use of antimycobacterial (rifampin, rifapentine) or enzyme-inducing anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin, etc.).
7. - Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
8. - Participants having a non-treated chronic HCV infection.
9. - Current or chronic history of liver disease or known hepatic or biliary abnormalities.
10. - Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) > 5-fold the upper normal limit (UNL).
11. - Creatinine clearance lower than 50 mL/min.
12. - History of chronic renal disease, osteoporosis or osteopenia.
13. - Inflammatory skin conditions which compromise the safety of intramuscular (IM) injections.
14. - Known thrombocytopenia or any other known bleeding disorder, which would contraindicate IM injection.
15. - Treatment with oral anticoagulant (antiplatelet agents are allowed).
16. - Known or suspected allergy to study product components.
17. - Surgically placed buttock implants.
18. - Planned trip abroad of more than 2 consecutive months or planned move outside the Ile de France region.
19. - Individuals who, upon the investigator’s judgement, will not be likely to comply the clinical trial procedures, or with any condition incompatible with study participation.
20. - Person participating in another research study with an exclusion period still in progress at inclusion.
21. - Person under guardianship or curatorship or deprived of liberty by judicial or administrative decision.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Completion of all protocol visits at Month 12 with a documented PrEP prescription of CAB or TDF/FTC at each study aligned with the randomization arm.

Secondary endpoints 22

1. Completion of all protocol visits at Month 24 with a documented PrEP prescription of CAB or TDF/FTC at each study aligned with the randomization arm
2. Causes of non-sustained PrEP use over time: missing follow-up visits defined by a visit occurring more than 15 days after the scheduled date, temporary PrEP discontinuation, permanent PrEP discontinuation, switching to another PrEP regimen different from the randomization arm, study discontinuation with PrEP cessation, study discontinuation while maintaining PrEP, and lost to follow-up.
3. PrEP coverage of the last condomless anal sexual intercourse based on self-report at each study visits. This information will be collected in the study eCRF.
4. Satisfaction regarding PrEP regimen measured by a self-administered questionnaire at baseline, 12 and 24 months
5. Number of sexual partners in the last 3 months evaluated by a self-administered questionnaire before the visits at baseline, 6, 12, 18 and 24 months.
6. Number of condomless anal sexual intercourse in the month prior each study visits. This information will be collected in the study eCRF.
7. Occurrence of syphilis, chlamydia, and gonorrhea infections at any time during the study.
8. Weight, blood pressure, fasting lipid level and HOMA index measured at baseline, 12, and 24 months.
9. Occurrence of Grade 2 or higher clinical or laboratory drug-related adverse events at any time during the study.
10. Injection site reaction and its severity evaluated by the investigator at each injection visits.
11. Perception of pain and injection site reactions by participants measured through a self-administrated questionnaire at baseline, 6, 12, 18 and 24 months.
12. PrEP regimen used in the month prior to each study visits (TDF/FTC: daily or on-demand, CAB group: CAB oral or CAB-LA). This information will be collected in the study eCRF.
13. Concentration of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in dried blood spots (DBS) at baseline.
14. Drugs concentrations in plasma measured at Months 6, 12, 18 and 24: o CAB Group: cabotegravir concentration in plasma. o TDF/FTC group: tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentration in dried blood spots (DBS).
15. Study visits occurring “on-time” (At Month 1: ±3 days, other visits: ±7 days).
16. Occurrence of HIV infection at any time during the study, defined as a positive HIV antibody immunoassay (4th generation) confirmed by the presence of HIV ribonucleic acid (RNA).
17. HIV drug resistance mutations among HIV-infected participants.
18. Use of psychoactive drugs in the last 3 months evaluated by a self-administered questionnaire before the visits at baseline, 6, 12, 18 and 24 months.
19. Quality of life measured by the EuroQol-5D questionnaire at baseline, 12 and 24 months.
20. Mental health measured by the Center for Epidemiologic Studies Depression Scale and the Rosenberg self-esteem scale at baseline, 12 and 24 months.
21. PrEP knowledge score evaluated by a self-administered questionnaire at baseline, 12 and 24 months.
22. Number and nature of uses of community peer support and therapeutic patient education measured through a self-administrated questionnaire at baseline, 6, 12, 18 and 24 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Inserm

Sponsor organisation

Inserm

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Inserm

Contact name

Aida TAIEB

Public contact point

Organisation

Inserm

Contact name

Aida TAIEB

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications