Clinical trial NCT06273943: Impact of Long-acting Injectable Cabotegravir for HIV PrEP in MSM in France.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Prevention
Keywords: HIV pre-exposure prophylaxis
PrEP
MSM
Long-acting injectable
cabotegravir
TDF/FTC
Persistence
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2024-02-23
Enrollment: 322
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned in a 1:1 ratio to remain on their current oral PrEP regimen with daily and/or on-demand TDF/FTC (Control arm) or to switch to a CAB-LA based PrEP (Intervention arm).
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate if offering long-acting injectable cabotegravir (CAB-LA) as an additional HIV prevention choice among oral PrEP-experienced men who have sex with men (MSM) in France can significantly increase the sustained PrEP use over time and the PrEP coverage of at-risk sexual risk behaviors.

Detailed description: Long-acting injectable cabotegravir (CAB-LA) is a promising agent to address the issue of uptake, adherence, and persistence among oral PrEP users who faced adherence challenges. However, the potential benefits of offering CAB-LA as an additional prevention option for MSM adherent to oral PrEP has yet to be demonstrated. We hypothesize that offering CAB-LA as an additional prevention option for MSM already using oral PrEP can mitigate PrEP fatigue over time, resulting in enhanced PrEP use and increased coverage of at-risk sexual intercourses.

This study is designed as a pragmatic, open-label, multicenter, parallel-group, randomized controlled clinical trial aiming to enroll MSM using PrEP for at least 6 months. Participants will be randomly assigned in a 1:1 ratio to remain on their current oral PrEP regimen with daily and/or on-demand TDF/FTC (Control arm) or to switch to a CAB-LA based PrEP (Intervention arm). Participants will be enrolled over 6 months and followed for two years. The trial will be conducted at 9 clinical sites in the Paris region. The primary objective of the study will be to compare the sustained PrEP use over time among participants randomized to CAB-LA vs. oral TDF/FTC based PrEP at Months 12 and 24. The main secondary objectives will aim to evaluate the PrEP coverage of at-risk sexual intercourses, the change from baseline in sexual risk behaviors, the safety of the drugs, and the HIV incidence.

The study protocol includes three ancillary studies:

* Social science: Focus groups will be conducted among study participants to investigate their perceptions of CAB-LA, motivations for using it, adherence and persistence, changes in HIV risk perception, and impact on sexual satisfaction. Additionally, this study will assess healthcare providers' perceptions, barriers, and facilitators regarding CAB-LA implementation for PrEP.
* Rectal tissue HIV-1 permissibility: This study aims to evaluate the protection from HIV-1 at different time points after oral and injectable CAB initiation using a model of Ex-vivo rectal tissue and PBMCs infection with HIV-1.
* Medico-economics analysis: The main objective of this study is to establish cost-effectiveness performance benchmarks for CAB-LA in HIV PrEP.

Eligibility criteria: Inclusion criteria

* Age ≥ 18 years.
* Cisgender men who have sex with men.
* Have taken oral TDF/FTC based PrEP during the past 6 months, either daily or on-demand, with a documented PrEP prescription.
* Agreeing to be contacted personally by telephone (call, SMS) or e-mail.
* Person affiliated with or a beneficiary of a social security scheme (article L1121-11 of the Public Health Code).
* 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).

Non-inclusion criteria

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

Primary outcomes:
measure: Number of protocol visits completed with a documented PrEP prescription aligned with the randomization arm.
timeFrame: At Month 12
Secondary outcomes:
measure: Number of protocol visits completed with a documented PrEP prescription aligned with the randomization arm.
timeFrame: At Month 24
measure: Number of participants with missing follow-up visits, temporary PrEP discontinuation, permanent PrEP discontinuation, switching to another PrEP regimen, study discontinuation, lost to follow-up.
timeFrame: At 12 and 24 Months.
measure: Number of participants whose last condomless anal sexual intercourse was not covered by PrEP.
timeFrame: At each study visits.
measure: Number of condomless anal sexual intercourse in the month prior to each study visit.
timeFrame: At each study visits.
measure: Number of sexual partners in the last 3 months.
timeFrame: At baseline, 6, 12, 18 and 24 months
measure: Mean PrEP satisfaction score based on study arm.
timeFrame: At baseline, 6, 12, 18 and 24 months.
measure: Number of participants with syphilis, chlamydiae, and/or gonorrhea infection.
timeFrame: From Day 1 up to end of study.
measure: Number of participants with Grade 2 or higher clinical or laboratory drug-related adverse events at any time during the study.
timeFrame: From Day 1 up to end of study.
measure: Change from baseline in body weight (kg).
timeFrame: At Months 12 and 24.
measure: Change from baseline in lipids
timeFrame: At Months 12 and 24.
measure: Change from baseline in the insulin resistance index (HOMA-IR).
timeFrame: At Months 12 and 24.
measure: Number and severity of injection site reaction.
timeFrame: After 12 and 24 Months.
measure: Cabotegravir concentration in plasma and tenofovir diphosphate and emtricitabine triphosphate concentration in dried blood spots.
timeFrame: At baseline, 6, 12, 18 and 24 months.
measure: Number of participants with new HIV infection.
timeFrame: From Day 1 up to end of study.
measure: Number of participants who used psychoactive drugs in the last 3 months
timeFrame: At baseline, 6, 12, 18 and 24 months.
measure: Score of quality of life measured by the EuroQol-5D questionnaire
timeFrame: At baseline, 6, 12, 18 and 24 months.
measure: Depression score assessed with the Center for Epidemiologic Studies Depression Scale (CES-D).
timeFrame: At baseline,12, and 24 months.
measure: Self-esteem score assessed with the Rosenberg scale.
timeFrame: At baseline,12, and 24 months.
measure: Number and nature of uses of community peer support and therapeutic patient education.
timeFrame: At baseline, 6, 12, 18 and 24 months.
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Hôtel Dieu
state: Ile De France
city: Paris
country: France
facility: Hôpital Lariboisière
state: Ile De France
city: Paris
country: France
facility: Hôpital Saint Louis
state: Ile De France
city: Paris
country: France
facility: Hôpital Saint Antoine
state: Ile De France
city: Paris
country: France
facility: Hôpital La Pitié Salpêtrière
state: Ile De France
city: Paris
country: France
facility: Hôpital Necker
state: Ile De France
city: Paris
country: France
facility: Hôpital Bichat
state: Ile De France
city: Paris
country: France
facility: Hôpital Tenon
state: Ile De France
Study officials:
affiliation: Saint-Louis Hospital, Paris, France
name: Jean-Michel Molina, Professor
role: PRINCIPAL_INVESTIGATOR
References: