CAbotégravir LENacapavir DUal Long Acting

NCT06657885 | Withdrawn Phase 2 DMC

• 2 other identifiers: IMEA 0692024-516028-33-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 12

Brief 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

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

Keywords

CAbotégravir LENacapavir DUal Long Acting

Outcome Measures

Primary Outcomes (2)

• Percentage of participants with virological failure

  week 48

• Percentage of participants with virological failure

  Week 24

Secondary Outcomes (16)

• Percentage of participants with virological failure

  Week 24, week48

• Percentage of participants achieving therapeutic success at W48 (absence of virological failure and definitive discontinuation of assigned treatment or study continuation due to intolerance). Change of residence, change of treatment due to pregnancy, for

  week 48

• Percentage of participants with viruses harbouring resistance mutations to the current treatment at the time of virological failure (by Sanger) and description of the resistance mutations selected at the time of virological failure.

  at the time of virologic failure

• Proportion of minority resistance variants archived in DNA at D0 and their impact on the risk of virological failure and on the selection of resistance mutations.

  D0

• Describe the evolution of the proportion of intact and defective proviruses in PBMC at D0 and W48.

  day 0 and week 48

Study Arms (1)

single-arm

EXPERIMENTAL

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

Interventions

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 DRUG

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

single-arm

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-2 infection or HIV-1/HIV2 co-infection
• HIV-1 subtype A6/A1
• BMI ≥ 30kg/m².
• Chronic active viral hepatitis B with positive Hbs antigen
• Active chronic viral hepatitis C requiring specific treatment over the next 48 weeks.
• Treatment with interferon, interleukin or any other immunotherapy or chemotherapy in progress.
• Active opportunistic infection, or acute treatment for opportunistic infection
• Any condition (alcohol, drugs, neurological or neuropsychiatric disorders, etc.) likely to compromise tolerance of treatment and/or patient compliance with treatment and adherence to the protocol, as judged by the investigator.
• Women who are breastfeeding, pregnant or refusing contraception
• Taking medication contraindicated with the trial treatment
• Major incapacity, legal protection, guardianship or curatorship
• Planning to move house within the next 18 months

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: collaborator
• Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba: lead

Study Sites (12)

Hopital Saint André

Bordeaux, France

Location

Hopiytal Pellegrin

Bordeaux, France

Location

Centre hospitalier François Mitterrand

Dijon, France

Location

Hopital raymond Poincaré

Garches, France

Location

Hôpital Franco-Britannique

Levallois-Perret, France

Location

CHU de nantes- Hotel Dieu

Nantes, France

Location

Chu- Nice Archet

Nice, France

Location

Hopital Saint Antoine

Paris, 75012, France

Location

Hopital Pitié Salpêtrière

Paris, 75013, France

Location

Hopital Necker

Paris, 75015, France

Location

Hopital Bichat Claude Bernard

Paris, 75018, France

Location

Centre hospitalier de Tourcoing

Tourcoing, France

Location

Study Officials

• Roland LANDMAN

  IMEA and Bichat hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2023
• First Posted: October 26, 2024
• Study Start: January 15, 2025
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): September 15, 2026
• Last Updated: January 14, 2026

Record last verified: 2024-09

Locations

FR (12)