Pilot study, open label, multicenter, evaluating dual antiretroviral therapy with long-acting cabotegravir/lenacapavir IMEA 069 - CALENDULA

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Inst Medecine Epidemiologie Appliquee

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

completed 26 Mar 2026

Decision date (initial)

2024-09-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

INSERM-ANRS-MIE

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of maintenance dual antiretroviral therapy with cabotegravir/lenacapavir over 48 weeks of follow-up. Efficacy being defined by the absence of virological failure: 2 successive CVs ≥50 copies/mL or a CV ≥50 copies/mL followed by definitive cessation of treatment or follow-up, or a CV ≥50 copies/mL at W48)

Secondary objectives 14

1. 1. The rate of virological failure between W24 and W48
2. 2. The rate of participants achieving therapeutic success at W48 (absence of virological failure and definitive discontinuation of treatment or study follow-up due to intolerance).
3. 3. Resistance profile at time of virological failure (by Sanger)
4. 4. Frequency 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.
5. 5. The evolution of the proportion of intact and defective proviruses in PBMC between D0 and W48.
6. 6. The rate 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.
7. 7. Change in CD4 and CD8 T lymphocytes and CD4/CD8 ratio between W-2 and W48.
8. 8. Plasma concentrations of antiretroviral treatments between D0 and W48
9. 9. Assessment of the incidence of grade 3 or higher clinical and laboratory adverse events.
10. 10. Assessment of the incidence of adverse events and discontinuation in the study up to W48.
11. 11. Development of weight and BMI between D0 and W48.
12. 12. Changes in metabolic parameters (total cholesterol, LDL-c, HDL-c, triglycerides and fasting plasma glucose) between D0 and W48.
13. 13. Changes in participants' symptoms (self-report) between D0 and W48
14. 14. Assessment of participant satisfaction (self-questionnaire) between D0 and W48.

Conditions and MedDRA coding

HIV infection

Regulatory references

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. - Age ≥ 18 years
2. - HIV-1 infection
3. - Stable oral antiretroviral treatment for at least 6 months
4. - 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
5. - ASAT and ALAT < 3N
6. - Creatinine Clearance> 60 mL/min (CKD-EPI)
7. - Haemoglobin > 10 g/dL
8. - Platelets > 100 000/mm3
9. - Commitment to use preventive and protective means of sexual intercourse for the duration of the trial
10. - For women at risk of pregnancy, commitment to use an effective method of contraception for the duration of the study.
11. - Affiliated or beneficiary of a social security scheme (article L1121-11 of the French Public Health Code),
12. - 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

Exclusion criteria 12

1. - HIV-2 infection or HIV-1/HIV2 co-infection
2. - HIV-1 subtype A6/A1
3. - BMI ≥ 30kg/m².
4. - Chronic active viral hepatitis B with positive Hbs antigen
5. - Active chronic viral hepatitis C requiring specific treatment over the next 48 weeks.
6. - Treatment with interferon, interleukin or any other immunotherapy or chemotherapy in progress.
7. - Active opportunistic infection, or acute treatment for opportunistic infection
8. - 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.
9. - Women who are breastfeeding, pregnant or refusing contraception
10. - Taking medication contraindicated with the trial treatment
11. - Major incapacity, legal protection, guardianship or curatorship
12. - Project to move in a non-study site within the next 18 months

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of participants with virological failure at week 48: i.2 consecutive CVs ≥50 copies/mL after achieving a CV <50 copies/mL; or ii. a CV ≥50 copies/mL followed by definitive cessation of treatment or follow-up after achieving a CV <50 copies/mL; or iii. a viral load CV ≥50 copies/mL at week 48. For patients detectable at baseline, virological failure will be assessed from week 24.

Secondary endpoints 14

1. Percentage of participants with virological failure between W24 and W48
2. 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, force majeure (inability to give an injection due to hospitalisation or travel abroad, etc.) and death unrelated to study treatment will not be considered as failures.
3. 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.
4. 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.
5. Describe the evolution of the proportion of intact and defective proviruses in PBMC at D0 and W48.
6. 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.
7. Change in CD4 and CD8 T lymphocytes and CD4/CD8 ratio between W-2 and W48
8. Description of plasma concentrations of antiretroviral treatments between D0 and W48
9. Incidence of clinical and laboratory grade 3 or higher adverse events
10. Incidence of adverse events and discontinuation from study to W48
11. Changes in weight and BMI from D0 to W48
12. Metabolic parameters (total cholesterol, LDL-c, HDL-c, triglycerides and fasting plasma glucose) from D0 to W48
13. Change in participants' symptoms as assessed by self-report questionnaire from D0 to W48
14. Assessment of participant satisfaction by questionnaire between D0 and W48

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Inst Medecine Epidemiologie Appliquee

Sponsor organisation

Inst Medecine Epidemiologie Appliquee

Address

46 Rue Henri Huchard

City

Paris

Postcode

75018

Country

France

Scientific contact point

Organisation

Inst Medecine Epidemiologie Appliquee

Contact name

ROLAND LANDMAN

Public contact point

Organisation

Inst Medecine Epidemiologie Appliquee

Contact name

ROLAND LANDMAN

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications