Doravirine for HIV-1 infection|HIV disease

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years, Patients with HIV-1 documented infection, CD4 ≥ 200/mm3"}
• {"criterion_text":"- On stable combined ART regimen with at least 2 drugs for at least 6 months"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Naive to doravirine"}
• {"criterion_text":"- Absence of resistance to doravirine* and/or raltegravir**(see list mutations below) -\ton all HIV-genotypes with available RT and integrase gene sequences allowing resistance interpretation in case of previous virological failure -\tor on DNA genotype performed at screening if HIV genotype is not available in case of prior virological failure."}
• {"criterion_text":"- Signed informed consent form."}
• {"criterion_text":"- 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

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

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Protocol virological failure is defined as two pVL > 50 copies/mL two weeks apart."}

Secondary endpoints

• {"endpoint_text":"- Proportion of patients maintaining viral suppression (pVL <50 copies/mL, Snapshot approach","definition_or_measurement_approach":"pVL <50 copies/mL assessed by FDA Snapshot approach"}
• {"endpoint_text":"- Evolution of CD4 and CD8 T-cells, and CD4/CD8 ratio","definition_or_measurement_approach":"Laboratory measurement of CD4 and CD8 T-cell counts and calculation of CD4/CD8 ratio over time"}
• {"endpoint_text":"- Proportion of patients with virological blips (HIV-RNA pVL>50 copies/mL followed by a second measurement <50 copies/mL)","definition_or_measurement_approach":"Blip defined as pVL >50 copies/mL followed by a second measurement <50 copies/mL"}
• {"endpoint_text":"- Resistance profile in case of protocol defined virological failure (PDVF)","definition_or_measurement_approach":"Genotypic resistance testing in case of PDVF"}
• {"endpoint_text":"- Proportion of patients with acquired resistance mutation among those with PDVF","definition_or_measurement_approach":"Proportion measured by genotypic analysis among PDVF cases"}
• {"endpoint_text":"- Frequency of grade 3 and 4 events","definition_or_measurement_approach":"Safety grading using standard toxicity grading scales (frequency of grade 3/4 adverse events)"}
• {"endpoint_text":"- Quality of life assessed by self-questionnaire at screening, D0, W24, W48, W72, W96","definition_or_measurement_approach":"Self-administered QoL questionnaire at specified visits"}
• {"endpoint_text":"- Observance assessed by self-questionnaire at D0, W24, W48, W96","definition_or_measurement_approach":"Self-administered adherence/observance questionnaire at specified visits"}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Measurement of HIV-RNA viral load and trough concentrations (Cmin) of drugs in male genital compartment at the specified visits (seminal sub-study)"}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Assessment of HIV viral suppression and CSF biomarkers (neuronal injury and inflammatory markers) at D0 and W48 in CSF sub-study"}

France

Latest Decision Or Authorization Date

29-01-2025

Number Of Sites

1

Number Of Participants

55

Italy

Latest Decision Or Authorization Date

28-01-2025

Number Of Sites

2

Number Of Participants

39

Spain

Latest Decision Or Authorization Date

13-12-2024

Number Of Sites

3

Number Of Participants

24

Primary sponsor

Full Name

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

Organisation Type

Health care

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"MERCK SHARP & DOHME CORP.","duties_or_roles":"Monetary support","organisation_type":""}