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

ANRS, Emerging Infectious Diseases

Status and phase: Not yet enrolling; Phase 3

Conditions: HIV-1-infection

Treatments: Drug: Doravirine + tenofovir DF + lamivudine; Drug: Dolutegravir + tenofovir DF + lamivudine or emtricitabine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06203132

ANRS 0392s ELDORADO

Details and patient eligibility

About

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

Full 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, Cambodia, Cameroon, Côte d'Ivoire, France and Mozambique.

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.

Enrollment: 610 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 of childbearing potential i.e. women 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.

Exclusion criteria

• Has ongoing (pulmonary or extra-pulmonary) tuberculosis (due to rifampin-doravirine drug-drug interaction)

• 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 documented or known resistance to study drugs (in France and where national guidelines recommend screening for primary resistance before starting first-line ART), as defined below:

  • Resistance to doravirine: V106A, V106M, Y188L, G190E/S, F227C, M230L, L100I+K103N, K103N+Y181C, K103N+P225H, at least 2 among: A98G, L100I, K101E, V106I, E138K, Y181C/V, G190A or H221Y
  • Resistance to dolutegravir QD: G118R, F121Y, E138A/K/T, G140A/C/S, N144D, Q148H/K/R, V151L, S153F/Y, N155H, S230R, R263K, T66K+L74M, L74I+E92Q, T66K.
  • Resistance to lamivudine/emtricitabine: K65R, T69INS, M184V/I, Q151M
  • Resistance to tenofovir: K65R/E/N, K70E, T69INS, at least 3 mutations among M41L, E44D, D67N, T69D/N/S, L74V/I, L210W, T215A/C/D/E/G/H/I/L/N/S/V/Y/F

• Have 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.

• Has a current (active) diagnosis of acute hepatitis, with AST (SGOT) and ALT (SGPT) >4.0 x ULN, due to any cause.

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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610 participants in 2 patient groups

Doravirine arm

Experimental group

Description:

Doravirine (100 mg) + tenofovir DF (300 mg) + lamivudine (300mg) administered daily

Treatment:

Drug: Doravirine + tenofovir DF + lamivudine

Dolutegravir arm

Active Comparator group

Description:

Dolutegravir (50 mg) + tenofovir DF 300 mg + XTC (300 mg if lamivudine ou 200 mg if emtricitabine) administered daily

Treatment:

Drug: Dolutegravir + tenofovir DF + lamivudine or emtricitabine