CAbotégravir LENacapavir DUal Long Acting

Summary

This study is a Phase II, prospective, single-arm, multicenter, non-randomized pilot study designed to evaluate the antiretroviral efficacy of lenacapavir in combination with cabotegravir injection over 48 weeks of follow-up in participants who meet the study inclusion criteria. Efficacy is defined as the absence of virologic failure at S48. Virologic success is defined as maintaining or achieving CV \< 50 copies/mL without interruption of long-acting dual therapy with cabotegravir/lenacapavir at the end of 48 weeks. The study will be conducted at several sites in France in adults 18 years of age and older. Minors and persons under legal guardianship will not be included in the study.

Long-acting treatments are evolving thanks to new "long-acting" molecules. These molecules ensure prolonged efficacy without the need for daily dosing thanks to their long half-life by oral / IM or SC injection (cabotegravir, islatravir, lenacapavir, rilpivirine and bNAbs).

Currently, the only available combination is dual therapy with cabotegravir/rilpivirine administered intramuscularly every two months. However, this injectable combination therapy has its limitations, namely previous resistance to rilpivirine, a number of failures due to certain virological subtypes or poor use of the injectable by certain patients (obesity, injection errors, etc.). For many referral centers caring for patients with HIV, it has become necessary to have a long-acting therapeutic alternative for certain patients. A strategy based on lenacapavir combined with cabotegravir could be a validated alternative for undetectable or detectable patients who have received intensive multidrug regimens, for patients with multidrug resistance, or for patients who are unable to take their oral antiretroviral regimens due to intolerance, drug-drug interactions, or non-adherence.

Recently in the US, the case series presented by Dr. Monica Gandhi (Case series examining the Long-Acting combination of Lenacapavir and Cabotegravir: call for a trial-abstract 629 CROI 2024) demonstrated the high virologic efficacy (94%) of this combination in participants who were unobserved, intolerant or had underlying resistance to antiretroviral therapy (NNRTIs).

The experimental drugs used in this study are cabotegravir, marketed as Vocabria®, and lenacapavir, marketed as Sunlenca®. Both are approved in France for the treatment of HIV-1 infection.

Conditions

• HIV1 Infection
• Multi-treated Patients Who Have Received Multiple Lines of Antiretroviral Treatment
• CABOTEGRAVIR
• LENACAPAVIR
• Stable Oral Antiretroviral Treatment for at Least 6 Months

Interventions

DRUG

his is a prospective, single-arm, multicentre, non-randomised phase II, pilot study designed to achieve or maintain virological success in participants who meet the prescribing criteria for lenacapavi

cabotegravir initiation: daily oral route of 1 tablet 30 mg at Day 0 to week 4 Cabotegravir maintennace: Every 8 weeks (+/- 1 week) intramuscular injection from week 8 at week 48. Lenacapavir initiation: Subcutaneous injection (927mg/3ml),ie 2 injections of 463,5mg/1,5mL in 2 distinct abdominal sites + orale route of 2 tablets of 300mg (ie 600 mg) at Day 0 and at day 1: orale route of 2 tablets of 300mg (ie 600 mg) Lenacapavir maintenance: Subcutaneous injection (927mg/3ml),ie 2 injections of 463,5mg/1,5mL in 2 distinct abdominal sites every 24 weeks (+/-1 week) from Day 0 to Week 48

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases

  collaborator OTHER_GOV

• Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba

  lead OTHER

Principal Investigators

• Roland LANDMAN · IMEA and Bichat hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

90 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-01-15

Primary Completion

2026-07-15

Completion

2026-09-15

Countries

• France

Study Locations