CAbotégravir LENacapavir DUal Long Acting (CALENDULA)

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

Status and phase

Not yet enrolling

Phase 2

Conditions

CABOTEGRAVIR

Stable Oral Antiretroviral Treatment for At Least 6 Months

Multi-treated Patients Who Have Received Multiple Lines of Antiretroviral Treatment

LENACAPAVIR

HIV1 Infection

Treatments

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

Study type

Interventional

Funder types

Other

Identifiers

NCT06657885

2024-516028-33-01 (EU Trial (CTIS) Number)

IMEA 069

Details and patient eligibility

About

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.

Enrollment

30 estimated patients

Sex

All

Ages

18 to 90 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Age ≥ 18 years

HIV-1 infection
Stable oral antiretroviral treatment for at least 6 months
Multi-treated patients who have received multiple lines of antiretroviral treatment
Undetectable patients with CV < 50 copies/mL in the last 6 months (a single blip between 50 and 200 copies/mL in the last 6 months is allowed) and eligible to switch to the lenacapavir/cabotegravir strategy on the basis of a collegial decision by clinicians, virologists and pharmacologists following a multidisciplinary meeting due to
the presence of resistance mutations, including to NNRTIs
or oral drug intolerance
or drug-drug interactions
Detectable, virologically uncontrolled HIV viral load ≥ 200 c/mL in the last 12 months who is eligible to switch to the lenacapavir/cabotegravir strategy based on a collegial decision by clinicians, virologists and pharmacologists following a multidisciplinary meeting due to
the presence of resistance mutations, including to NNRTIs
or oral drug intolerance
or drug-drug interactions
ASAT and ALAT < 3N
Creatinine GFR > 60 mL/min (CKD-EPI)
Haemoglobin > 10 g/dL
Platelets > 100 000/mm3
Commitment to use preventive and protective means of sexual intercourse for the duration of the trial.
For women at risk of pregnancy, commitment to use an effective method of contraception for the duration of the study.
Affiliated or beneficiary of a social security scheme (article L1121-11 of the French Public Health Code),
Free, informed, written consent, signed by the person and the investigator no later than the day of inclusion and before any examination carried out as part of the study (article L1122-1-1 of the French Public Health Code).

Non-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
Major incapacity, legal protection, guardianship or curatorship
Planning to move house within the next 18 months