Clinical trial NCT06203132: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: HIV-1-infection
Keywords: HIV-1
ART-naïve
doravirine
dolutegravir
non-inferiority
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: MSD France
name: European and Developing Countries Clinical Trials Partnership (EDCTP)
First posted: 2024-01-12
Enrollment: 610
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: 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
timeFrame: Week 48
Secondary outcomes:
Other outcomes:
Locations:
city: Nova Iguaçu
country: Brazil
facility: Hospital Geral de Nova Iguaçu
state: RJ
city: Rio De Janeiro
country: Brazil
facility: Laboratory on Clinical research on AIDS-INI FIOCRUZ
state: RJ
city: Yaoundé
country: Cameroon
facility: Hôpital Central de Yaoundé
city: Abidjan
country: Côte D'Ivoire
facility: Centre de prise en charge de Recherche et de Formation (CEPREF)
city: Abidjan
country: Côte D'Ivoire
facility: Centre Médical de Suivi des Donneurs de Sang (CMSDS) - Centre National de Transfusion Sanguine (CNTS)
city: Abidjan
country: Côte D'Ivoire
facility: CHU de Treichville, Service des Maladies Infectieuses et Tropicales (SMIT)
city: Bordeaux
country: France
facility: CHU Bordeaux Pellegrin - Service des Maladies Infectieuses et Tropicales
city: Bordeaux
country: France
facility: CHU Bordeaux St André - Service de Médecine Interne
city: Montpellier
country: France
facility: CHU Montpellier - Hôpital La Colombière - Service des Maladies Infectieuses et Tropicales
city: Nantes
country: France
facility: CHU Nantes Hôtel Dieu - Service des Maladies infectieuses et tropicales
city: Paris
country: France
facility: AP-HP Hôpital Lariboisière - Service de Maladies Infectieuses et Tropicales
city: Paris
country: France
facility: AP-HP Hôpital Saint Louis - Service des Maladies Infectieuses et Tropicales
city: Paris
country: France
facility: AP-HP Hôpital Saint Antoine - Service des Maladies Infectieuses et Tropicales
city: Paris
country: France
facility: AP-HP Hôpital Pitié Salpêtrière - Service des Maladies Infectieuses et Tropicales
city: Paris
country: France
facility: AP-HP Bichat Claude Bernard - Service des Maladies Infectieuses et Tropicales
city: Maputo
country: Mozambique
facility: Centro de Saúde 1o de Maio
city: Chiangrai
country: Thailand
facility: Chiangrai Prachanukroh
city: Lampang
country: Thailand
facility: Lampang Hospital Internal Medicine department
city: Phayao
country: Thailand
facility: Phayao Hospital Internal Medicine department
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Pierre SELLIER, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: IPEC-FIOCRUZ
name: Beatriz GRINSZTEJN, Pr
role: PRINCIPAL_INVESTIGATOR
References: