DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection

Official title

Phase III, Open-label, Randomized, Multicenter Trial EvaLuating the Non-inferiority of DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection

Overview

Phase III trial evaluating doravirine as an alternative to dolutegravir in treatment naïve people living with HIV-1 infection.

Detailed description

Phase III, multicenter, open-label, randomized, non-inferiority clinical trial which aims to assess the non-inferiority of doravirine in association with tenofovir and lamivudine, as compared to dolutegravir in association with tenofovir and lamivudine or emtricitabine.

This trial will be implemented in Brazil, Cameroon, Côte d'Ivoire, France, Mozambique and Thailand.

Six hundred and ten patients will be enrolled and followed for 96 weeks after entry in the trial (=ART initiation).

Primary endpoint will assess virological efficacy at Week 48, measured by the proportion of subjects achieving HIV-1 RNA \<50 copies/mL, in HIV-1 infected, treatment-naive subjects with pre-treatment viral load (HIV-1 RNA) ≥ 1,000 copies/mL.

Secondary endpoints are planned at W48 and W96.

Interventions

• Drug Doravirine + tenofovir DF + lamivudine
  Oral administration
• Drug Dolutegravir + tenofovir DF + lamivudine or emtricitabine
  Oral administration

Primary outcome measures

• Non-inferiority of doravirine in combination with tenofovir and lamivudine as compared to dolutegravir in combination with tenofovir and lamivudine or emtricitabine in terms of virological efficacy at week 48 [Time frame: Week 48]

Secondary outcome measures (12)

• Occurrence of obesity [Time frame: Week 48; Week 96]
• Occurrence of insulin resistance [Time frame: Week 48; Week 96]
• Occurrence of hypertension [Time frame: Week 48; Week 96]
• Non-inferiority of DOR in association with TDF and 3TC, compared to DTG in association with TDF and 3TC or FTC, in terms of virologic efficacy [Time frame: Week 96]
• Occurrence of virological failures [Time frame: Virological failure]
• Occurrence of HIV-1 drug resistances in patients with confirmed virological failure [Time frame: Virological Failure]
• Virological efficacy at a threshold of HIV 1 RNA<200 copies/mL [Time frame: Week 48; Week 96]
• Virological efficacy at a threshold of HIV 1 RNA<1000 copies/mL [Time frame: Week 48; Week 96]
• Effect of baseline RT and integrase mutations on virological response [Time frame: Week 48; Week 96]
• Occurrence of combined overweight and obesity [Time frame: Week 48; Week 96]
• Occurrence of weight gain ≥10% absolute body weight [Time frame: Week 48; Week 96]
• Changes in absolute weight gain [Time frame: Week 48; Week 96]

Eligibility criteria

Inclusion criteria

• Be at least 18 years of age on the day of signing the informed consent.
• Be HIV-1 positive as determined according to national testing strategies
• Have a plasma HIV-1 RNA ≥1000 copies/mL within 30 days prior to the randomization,
• Have HIV treatment indication based on physician assessment according to local treatment guidelines
• Be naïve to antiretroviral therapy (ART) including investigational antiretroviral agents
• For women or transgender men of childbearing potential i.e. of childbearing age who are not menopausal, or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy) or not refraining from sexual activity: negative urinary test for pregnancy and acceptance to use contraceptive methods
• Understand the study procedures and voluntarily agree to participate by giving written informed consent for the trial.

Non-inclusion Criteria:

• Has ongoing (pulmonary or extra-pulmonary) tuberculosis
• Has any other history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate.
• Is infected with HIV-2 or co-infected with HIV-1 and HIV-2
• Has received cabotegravir long acting or dapivirine pre-exposure prophylaxis (PrEP).
• Has received oral pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) in the past three months or has had no negative HIV-1 serology performed
• Has documented or known resistance or possible resistance to study drugs (in France and where national guidelines recommend screening for primary resistance before starting first-line ART) as defined by the ANRS MIE AC43 Resistance group
• Has the following laboratory values at screening visit, within 30 days prior to the randomization:

• AST (SGOT) and ALT (SGPT) >4.0 x upper limit of normal
• Estimated glomerular filtration rate at time of screening <60 mL/min/1.73m², based on the CKD-EPI equation
• Has participated in a study with an investigational compound/device within 30 days prior to signing informed consent or anticipates participating in such a study involving an investigational compound/device during the course of this study.
• Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study
• Requires or is anticipated to require any of the prohibited or contraindicated medications noted in the trial protocol.
• Has significant hypersensitivity or other contraindication to any of the components of the study drugs.
• Is pregnant, breastfeeding, or expecting to conceive at any time during the study.
• Has any condition which might, in the investigator's opinion, compromise the safety of treatment and/or patient's adherence to study procedure.
• Is a person under guardianship or deprived of freedom by a judicial or administrative decision

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 9 centers

• CHU Bordeaux Pellegrin - Service des Maladies Infectieuses et Tropicales — Bordeaux
• CHU Bordeaux St André - Service de Médecine Interne — Bordeaux
• CHU Montpellier - Hôpital La Colombière - Service des Maladies Infectieuses et Tropicales — Montpellier
• CHU Nantes Hôtel Dieu - Service des Maladies infectieuses et tropicales — Nantes
• AP-HP Hôpital Lariboisière - Service de Maladies Infectieuses et Tropicales — Paris
• AP-HP Hôpital Saint Louis - Service des Maladies Infectieuses et Tropicales — Paris
• AP-HP Hôpital Saint Antoine - Service des Maladies Infectieuses et Tropicales — Paris
• AP-HP Hôpital Pitié Salpêtrière - Service des Maladies Infectieuses et Tropicales — Paris
• … and 1 more center

Côte d’Ivoire · 3 centers

• Centre de prise en charge de Recherche et de Formation (CEPREF) — Abidjan
• Centre Médical de Suivi des Donneurs de Sang (CMSDS) - Centre National de Transfusion Sang — Abidjan
• CHU de Treichville, Service des Maladies Infectieuses et Tropicales (SMIT) — Abidjan

Thailand · 3 centers

• Chiangrai Prachanukroh — Chiang Rai
• Lampang Hospital Internal Medicine department — Lampang
• Phayao Hospital Internal Medicine department — Phayao

Brazil · 2 centers

• Hospital Geral de Nova Iguaçu — Nova Iguaçu
• Laboratory on Clinical research on AIDS-INI FIOCRUZ — Rio de Janeiro

Cameroon · 1 center

• Hôpital Central de Yaoundé — Yaoundé

Mozambique · 1 center

• Centro de Saúde 1o de Maio — Maputo

Publications

• L'hostellier A, Kouanfack C, Chazallon C, Wagner-Cardoso S, Eholie SP, Banze N, Halue G, Capeau J, Delaugerre C, Moh R, Bonnet F, Mfeukeu Kuate L, Jaquet A, Perazzo H, Bernard C, Bastard JP, Goldwirt L, Vilquin P, Nhassengo PP, Lavalee M, Minvielle N, Dodd PJ, Marcy O, Molina JM, Grinsztejn B, Sellier PO. Doravirine versus dolutegravir-based regimen in antiretroviral treatment-naive people living PMID 41644158

Identifiers

NCT: NCT06203132 · ANRS 0392s ELDORADO

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗