CAbotégravir LENacapavir DUal Long Acting (CALENDULA)

Phase II, Pilot Study, Open Label, Multicenter, Evaluating Dual Antiretroviral Therapy With Long-acting Cabotegravir/Lenacapavir

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.

Study Overview

• Status: Withdrawn
• 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
• Intervention / Treatment: 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
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • Hopital Saint André
  • Bordeaux, France
    • Hopiytal Pellegrin
  • Dijon, France
    • Centre hospitalier François Mitterrand
  • Garches, France
    • Hôpital Raymond Poincaré
  • Levallois-Perret, France
    • Hôpital Franco-Britannique
  • Nantes, France
    • CHU de Nantes- Hotel Dieu
  • Nice, France
    • Chu- Nice Archet
  • Paris, France, 75012
    • Hôpital Saint Antoine
  • Paris, France, 75013
    • Hôpital Pitié Salpêtrière
  • Paris, France, 75018
    • Hopital Bichat Claude Bernard
  • Paris, France, 75015
    • Hôpital Necker
  • Tourcoing, France
    • Centre Hospitalier de Tourcoing

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: single-arm

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with virological failure	week 48
Percentage of participants with virological failure	Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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
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
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
Metabolic parameters (total cholesterol, LDL-c, HDL-c, triglycerides and fasting plasma glucose) from D0 to W48	Between 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	week24 and week 48
Percentage of participants with virological failure	week24

Collaborators and Investigators

• Sponsor: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
• Collaborators: ANRS, Emerging Infectious Diseases
• Investigators: Principal Investigator: Roland LANDMAN, IMEA and Bichat hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 15, 2025
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): September 15, 2026

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 26, 2024

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: CAbotégravir LENacapavir DUal Long Acting
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Benzocaine
• Other Study ID Numbers: IMEA 069; 2024-516028-33-01 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No