Modulo

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre De Recherches Et D'Etudes Sur La Pathologie Tropicale Et Le Sida, ANRS Maladies Infectieuses Emergentes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

30 Apr 2025 → ongoing

Decision date (initial)

2025-01-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Agence Nationale de Recherche sur les hépatites, le VIH/SIDA et les Maladies Infectieuses Emergentes

External identifiers

EU CT number

2024-515793-27-01

ClinicalTrials.gov

NCT06774872

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The main objective of the MODULO trial is to compare (non-inferiority) the capacity of DOR/3TC and DTG/3TC two-drug regimens of maintain virological success at W48 in PLWH with suppressed HIV plasma viral load (pVL) under three-drug regimen at inclusion.
The virological success is defined as no virological failure (2 consecutive pVL ≥50 copies/mL or one pVL ≥50 copies/mL followed with discontinuation of treatment or follow-up).

Secondary objectives 12

1. The secondary objectives of the MODULO trial are to assess between inclusion (D0) and W48 the following parameters:• Rate of virological failures
2. Rate of therapeutic success (no virological failure and no discontinuation of treatment or follow-up, using FDA Snapshot approach);
3. Mutations of resistance in case of virological failure;
4. Rate of “blips” (single pVL ≥50 copies/mL, with next pVL <50 copies/mL);
5. Residual plasma drug concentrations;
6. Incidence of clinical and biological side effects, with or without treatment discontinuation;
7. Evolution of CD4 T-cell counts, CD8 T-cell counts and CD4/CD8 ratio;
8. Evolution of weight and BMI;
9. Evolution of metabolic biomarkers (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glycemia);
10. Evolution of HIV reservoir (total HIV-DNA in blood);
11. Proportion of participants with residual viremia (pVL <20 copies/mL with detectable RT-PCR signal);
12. Evolution of the satisfaction associated to the study treatments (self-questionnaire). All these parameters will be also evaluated at W96.

Conditions and MedDRA coding

HIV

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. • Adults ≥18 years;
2. • Living with HIV-1;
3. • With pVL <50 copies/mL for at least 24 months;
4. • Under stable (7 days/7, 5 days/7 or 4 days/7) three-drug regimen including 2 NRTIs + 1 NNRTI or 1 INSTI or 1 boosted PI for at least 6 months;
5. • Affiliated to the French Social Insurance;
6. • Who have given their written consent to participate in the study.
7. • Patients with a DNA genotype in which the integrase gene could not be amplified, - And who have never been exposed to integrase inhibitors, - Or who have previously been exposed to integrase inhibitors, but without a history of virological failure;

Exclusion criteria 8

1. • HIV-2 co-infection;
2. • Co-infection with hepatitis B virus (positive HBsAg and/or positive anti-HBc antibody with negative anti-HBs antibody);
3. • Documented resistance mutation or association of resistance mutations, associated with partial or full resistance to doravirine, dolutegravir or lamivudine, using the last version of the ANRS-MIE algorithm;
4. • At least one resistance genotype is mandatory to include the patient: o If there was no virological failure under NRTI, NNRTI and INSTI in the past: - Pretherapeutic HIV-RNA genotype, - OR, in case of no available HIV-RNA genotype, genotype on proviral HIV-DNA to performed before inclusion, o In case of virological failure under NRTI, NNRTI and INSTI in the past: - HIV-RNA genotype at time of virological failure, - OR, in case of no available HIV-RNA genotype at time of failure, genotype on proviral HIV-DNA to performed before inclusion to be sure that the virus is fully sensitive to the study treatments, o Past virological failure is defined as: 2 consecutive pVL ≥50 copies/mL or one pVL ≥200 copies/mL, o Resistance genotypes will be interpretated with the last available ANRS algorithm.
5. • Glomerular filtration rate <50 mL/min (CKD-EPI formula);
6. • Comedications leading to drug-drug interaction with one of the 3 study drugs (cf. detailed protocol);
7. • Pregnant or breastfeeding women, and women with age to be pregnant but refusing contraception;
8. • Any clinal condition limiting the participation in a clinical trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants with virological failure at W48 (2 consecutive pVL >50 copies/mL with a delay of 2-4 weeks).

Secondary endpoints 13

1. Proportion of participants with virological failure at W96;
2. Proportion of participants with discontinuation of treatment or follow-up over 96 weeks;
3. Proportion of participants with new resistance associated mutations in case of virological failure;
4. Plasma drug concentrations at W24, W48, W72 and W96, and in case of virological failure;
5. Proportion of participants with severe biological or clinical side effect over 96 weeks;
6. CD4 and CD8 T-cell counts, CD4/CD8 ratio at D0, W48 and W96;
7. Body weight and BMI et IMC at D0, W48 and W96;
8. Metabolic biomarkers (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glycemia) at D0, W48 and W96;
9. Levels of total HIV-DNA in PBMC at D0, W48 and W96;
10. Proportion of participants with residual viremia at D0, W48 and W96;
11. Levels of satisfaction associated with study treatments at D0, W48 and W96 (HIVTSQ questionnaire);
12. Drug concentrations in female genital secretion or semen at W24 and W48 (among participants of the “genital compartment” sub-study);
13. Levels of HIV-RNA in female genital secretion or semen at W24 and W48 (among participants of the “genital compartment” sub-study).

Investigational products

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

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre De Recherches Et D'Etudes Sur La Pathologie Tropicale Et Le Sida

Sponsor organisation

Centre De Recherches Et D'Etudes Sur La Pathologie Tropicale Et Le Sida

Address

Pavillon Laveran, 91 Boulevard De L Hopital 91 Boulevard De L Hopital

City

Paris Cedex 13

Postcode

75634

Country

France

Scientific contact point

Organisation

Centre De Recherches Et D'Etudes Sur La Pathologie Tropicale Et Le Sida

Contact name

Dr Romain PALICH

Public contact point

Organisation

Centre De Recherches Et D'Etudes Sur La Pathologie Tropicale Et Le Sida

Contact name

Dr Romain PALICH

ANRS Maladies Infectieuses Emergentes

Sponsor organisation

ANRS Maladies Infectieuses Emergentes

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Sponsor responsibilities

Article 77 compliance

Centre De Recherches Et D'Etudes Sur La Pathologie Tropicale Et Le Sida

Contact point sponsor

Centre De Recherches Et D'Etudes Sur La Pathologie Tropicale Et Le Sida

Article 77 implementation

Centre De Recherches Et D'Etudes Sur La Pathologie Tropicale Et Le Sida

Locations

1 EU/EEA country · 37 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 35 files

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

Application history

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