Impact of Long-acting Injectable Cabotegravir for HIV PrEP in MSM in France. (CABOPrEP)

ANRS, Emerging Infectious Diseases

Status and phase: Not yet enrolling; Phase 3

Conditions: Prevention

Treatments: Procedure: Rectal Biopsies; Drug: Tenofovir disoproxil/Emtricitabine 300mg/200mg fixed-dose combination tablets, for oral use; Drug: Cabotegravir Extended-Release Injectable Suspension, for intramuscular use.; Drug: Cabotegravir Tablets, for oral use.

Study type: Interventional

Funder types: Other

Identifiers

NCT06273943

ANRS 0410s CABOPrEP

2024-510678-25 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 322 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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322 participants in 2 patient groups

Oral PrEP with daily or on-demand TDF/FTC

Active Comparator group

Description:

Participants randomly assigned to the oral PrEP regimen will be instructed to take a single dose combination of TDF 300 mg + FTC 200 mg (TDF/FTC), either daily or on-demand, according to their preferences.

Treatment:

Drug: Tenofovir disoproxil/Emtricitabine 300mg/200mg fixed-dose combination tablets, for oral use

Procedure: Rectal Biopsies

Long-acting injectable PrEP with cabotegavir

Experimental group

Description:

Participants assigned to the cabotegravir group will initially take a 30mg oral tablet of cabotegravir daily for a four-week period. Following this initial phase, they will receive 13 intramuscular injections of 600mg (3mL) long-acting injectable cabotegravir (CAB-LA) administered every two months after an initial loading dose given one month after the last oral tablet.

Treatment:

Drug: Cabotegravir Tablets, for oral use.

Drug: Cabotegravir Extended-Release Injectable Suspension, for intramuscular use.

Procedure: Rectal Biopsies