A randomized comparative phase II trial evaluating the capacity of the dualcombination doravirine/raltegravir to maintain virological success in HIV-1infected patients with an HIV-RNA plasma viremia below 50 copies/mL under acurrent antiretroviral regimen.
- Conditions
- HIV-1 INFECTIONTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2019-004195-19-IT
- Lead Sponsor
- Centre de Recherche et d’Etudes sur la Pathologie Tropical et le Sida (CREPATS)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 150
Age = 18 years
• Patients with HIV-1 documented infection
• CD4 = 200/mm3
• On stable combined ART regimen with at least 2 drugs for at least 6
months
• HIV-RNA plasma VL = 50 copies/mL during the last 12 months prior to
screening visit (W-6/W-4), documented by at least 2 time-points with no
more than one blip (defined as one HIV-RNA plasma VL between 51 and
200 copies/mL followed by one HIV-RNA plasma VL = 50 copies/mL)
• Naive to doravirine
• 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.
• Signed informed consent form.
• 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).
*Mutations associated to doravirine resistance are: V106A/M, Y188L, G190E/S,
M230L, F227C, at least 2 among: A98G, L100I, K101E, V106I,
E138K, Y181C/V, G190A or H221Y
**Mutations associated to raltegravir resistance are: T66A/K, E92Q, G118R,
F121Y, G140A/S Y143A/C/G/H/R/S, Q148E/G/H/K/R, V151L, N155H/S/T,
E157Q, S230R, R263K, L74 F/I + V75I
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5
• Absence of RT and INI HIV sequence available (past genotypes or failure
of amplification of DNA at screening)
• HBV co-infection
• Hemoglobin <9 g/dL
• Platelets <80,000/mm3
• Creatinine clearance <60 mL/min (MDRD)
• AST or ALT =5N
• Concomitant DAA for anti-HCV therapy
• Any severe concomitant illness
• Any drug with potential drug-drug interaction with doravirine
• Concomitant treatment using interferon, interleukins or any other immunetherapy
or chemotherapy
• Concomitant prophylactic or curative treatment for an opportunistic
infection
• All conditions (use of alcohol, drugs, etc.) judged by the investigator to
possibly interfere with trial protocol compliance, adherence and/or trial
treatment tolerance
• Subjects under sauvegarde de justice (judicial protection due to
temporarily and slightly diminished mental or physical faculties), or under
legal guardianship
• Subjects participating in another clinical trial evaluating different therapies
and including an exclusion period that is still in force during the screening
phase
• Pregnant women or breastfeeding women
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the virological efficacy at week 48 of once daily doravirine plus<br>raltegravir dual therapy in HIV-1-infected patients suppressed on ART;Secondary Objective: To evaluate over 96 weeks:<br>• Virological efficacy of the doravirine plus raltegravir dual therapy<br>• To assess the proportion of patients in therapeutic success up to week<br>48 and week 96<br>• Resistance profile in case of virological failure<br>• Evolution of CD4 and CD8 T-cells, and CD4/CD8 ratio<br>• Clinical and biological tolerability of the doravirine plus raltegravir dual<br>therapy<br>• Quality of life questionnaire<br>• Observance questionnaire<br>• Evolution of HIV-reservoir (Whole blood will be collected at D0, W48 and<br>W96)<br>;Primary end point(s): The primary endpoint is the proportion of patients with<br>virological failure before or at week 48.<br>Protocol virological failure is defined as two pVL>50 copies/mL two weeks apart;Timepoint(s) of evaluation of this end point: WEEK 48
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: WEEK 96;Secondary end point(s): To evaluate over 96 weeks:<br>• Proportion of patients maintaining viral suppression (pVL <50 copies/mL,<br>Snapshot approach)<br>• Evolution of CD4 and CD8 T-cells, and CD4/CD8 ratio<br>• Proportion of patients with virological blips (HIV-RNA pVL>50 copies/mL<br>followed by a second measurement <50 copies/mL)<br>• Resistance profile in case of protocol defined virological failure (PDVF)<br>• Proportion of patients with acquired resistance mutation among those with<br>PDVF<br>• Frequency of grade 3 and 4 events<br>• Quality of life assessed by self-questionnaire at screening, D0, W24,<br>W48, W72, W96<br>• Observance assessed by self-questionnaire at D0, W24, W48, W96<br>• Evolution of total cell HIV-DNA in PBMC from D0 to W48 and W96