Phase II, Pilot Study, Open Label, Multicenter, Evaluating Dual Antiretroviral Therapy With Long-acting Cabotegravir/Lenacapavir
Overview
- Phase
- Phase 2
- Intervention
- 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
- Conditions
- HIV1 Infection
- Sponsor
- Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
- Enrollment
- 30
- Locations
- 12
- Primary Endpoint
- Percentage of participants with virological failure
- Status
- Withdrawn
- Last Updated
- 3 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- Not provided
Arms & Interventions
single-arm
Intervention: 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
Outcomes
Primary Outcomes
Percentage of participants with virological failure
Time Frame: Week 24
Percentage of participants with virological failure
Time Frame: week 48
Secondary Outcomes
- Metabolic parameters (total cholesterol, LDL-c, HDL-c, triglycerides and fasting plasma glucose) from D0 to W48(Between day 0 and week 48)
- Percentage of participants with virological failure(week24)
- 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)
- Percentage of participants with at least one "blip" (viral load greater than 50 copies/mL with a control less than or equal to 50 copies/mL) between D0 and W48.(Between day 0 and week 48)
- Change in CD4 and CD8 T lymphocytes and CD4/CD8 ratio between W-2 and W48(Week -2 and week 48)
- Incidence of adverse events and discontinuation from study to W48(Between day 0 and week 48)
- Changes in weight and BMI from D0 to W48(Between day 0 and week 48)
- Description of plasma concentrations of antiretroviral treatments between D0 and W48(between day0 and week 48)
- Incidence of clinical and laboratory grade 3 or higher adverse events(betwwen Day 0 and week 48)
- Change in participants' symptoms as assessed by self-report questionnaire from D0 to W48(Between day 0 and week 48)
- Assessment of participant satisfaction by questionnaire between D0 and W48(Between day 0 and week 48)
- Percentage of participants with virological failure(Week 24, week48)
- Percentage of participants with virological failure(week24 and week 48)