Doral

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre de Recherches et d’Etudes sur les Pathologies Infectieuses, Tropicales et le VIH/Sida

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2025-01-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

MERCK SHARP & DOHME CORP.

External identifiers

EU CT number

2024-513941-35-00

EudraCT number

2019-004195-19

ClinicalTrials.gov

NCT04513626

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the virological efficacy at week 48 of once daily doravirine plus raltegravir dual therapy in HIV-1 infected patients suppressed on ART.

Secondary objectives 7

1. To assess HIV-RNA viral load and Cmin (Minimal Drug Concentration) of doravirine/raltegravir at D0, W24 and W48 visits for patients in “Immediate switch” arm and D0, W72 and W96 visits for patients in “delayed switch” arm in human male genital compartment (Seminal sub-study, 30 patients included in the french centers)
2. Virological efficacy of the doravirine plus raltegravir dual therapy
3. To assess the proportion of patients in therapeutic success up to week 48 and week 96
4. Resistance profile in case of virological failure
5. Evolution of CD4 and CD8 T-cells, and CD4/CD8 ratio
6. Clinical and biological tolerability of the doravirine plus raltegravir dual therapy
7. Quality of life questionnaire, Observance questionnaire

Conditions and MedDRA coding

HIV Disease

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥ 18 years, Patients with HIV-1 documented infection, CD4 ≥ 200/mm3
2. On stable combined ART regimen with at least 2 drugs for at least 6 months
3. HIV-RNA plasma VL ≤ 50 copies/mL during the last 18 months prior to/or including screening visit (W-6/W-4), documented by at least 2 time-points with authorization of an isolated HIV-RNA plasma VL between 50 to 400 copies/mL followed by one HIV-RNA plasma VL ≤ 50 copies/ml
4. Naive to doravirine
5. Absence of resistance to doravirine* and/or raltegravir**(see list mutations below) - on all HIV-genotypes with available RT and integrase gene sequences allowing resistance interpretation in case of previous virological failure - or on DNA genotype performed at screening if HIV genotype is not available in case of prior virological failure.
6. Signed informed consent form.
7. Patient affiliated to a social insurance regimen. For French patients only: subject enrolled in or a beneficiary of a Social Security programme (State Medical Aid or AME is not a Social Security programme).

Exclusion criteria 13

1. Absence of RT and INI HIV sequence available (past genotypes or failure of amplification of DNA at screening) in case of previous virological failure.
2. HBV co-infection
3. Hemoglobin <9 g/dL* (*Being a hemophiliac is not an exclusionary criterion)
4. Platelets <80,000/mm3, Creatinine clearance <60 mL/min (MDRD), AST or ALT ≥5N
5. Concomitant DAA for anti-HCV therapy
6. Any severe concomitant illness
7. Any drug with potential drug-drug interaction with doravirine
8. Concomitant treatment using interferon, interleukins or any other immune-therapy or chemotherapy
9. Concomitant prophylactic or curative treatment for an opportunistic infection
10. All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with trial protocol compliance, adherence and/or trial treatment tolerance
11. Subjects under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties), or under legal guardianship
12. Subjects participating in another clinical trial evaluating different therapies and including an exclusion period that is still in force during the screening phase
13. Pregnant women or women with a desire to become pregnant or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients with virological failure before or at week 48. Protocol virological failure is defined as two pVL>50 copies/mL two weeks apart.

Secondary endpoints 10

1. Proportion of patients maintaining viral suppression (pVL <50 copies/mL, Snapshot approach
2. Evolution of CD4 and CD8 T-cells, and CD4/CD8 ratio
3. Proportion of patients with virological blips (HIV-RNA pVL>50 copies/mL followed by a second measurement <50 copies/mL)
4. Resistance profile in case of protocol defined virological failure (PDVF)
5. Proportion of patients with acquired resistance mutation among those with PDVF
6. Frequency of grade 3 and 4 events
7. Quality of life assessed by self-questionnaire at screening, D0, W24, W48, W72, W96
8. Observance assessed by self-questionnaire at D0, W24, W48, W96
9. To assess HIV-RNA viral load and Cmin (Minimal Drug Concentration) of doravirine/raltegravir D0, W24 and W48 visits for patients in “Immediate switch” arm and D0, W72 and W96 visits for patients in “delayed switch” arm in human male genital compartment (30 patients included in the french centers)
10. Evaluate the maintenance of HIV viral suppression as well as changes in neuronal injury and inflammatory markers in cerebrospinal fluid (CSF) at D0 and W48 (CSF sub-study, 15 patients included in the Spanish centers)

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre de Recherches et d’Etudes sur les Pathologies Infectieuses, Tropicales et le VIH/Sida

Sponsor organisation

Centre de Recherches et d’Etudes sur les Pathologies Infectieuses, Tropicales et le VIH/Sida

Address

Hôpital Pitié-Salpêtrière, Maladies Infectieuses et Tropicales, Pavillon Laveran, 47-83 Boulevard de l'hôpital Maladies Infectieuses et Tropicales Pavillon Laveran

City

PARIS

Postcode

75651 Cedex 13

Country

France

Scientific contact point

Organisation

Centre de Recherches et d’Etudes sur les Pathologies Infectieuses, Tropicales et le VIH/Sida

Contact name

Dr Romain PALICH

Public contact point

Organisation

Centre de Recherches et d’Etudes sur les Pathologies Infectieuses, Tropicales et le VIH/Sida

Contact name

Dr Romain PALICH

Locations

3 EU/EEA countries · 6 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 22 files

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

Application history

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