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

HIV-1-infection Clinical Trial

— ELDORADO  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06203132
• Other study ID #: ANRS 0392s ELDORADO
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 2024
• Est. completion date: April 2027

Study information

• Verified date: January 2024
• Source: ANRS, Emerging Infectious Diseases
• Contact: Anthony L'HOSTELLIER
• Phone: 33 (0)5 57 57 13 93
• Email: anthony.lhostellier[@]u-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 610
• Est. completion date: April 2027
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• HIV-1-infection
• Infections

Intervention

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

Locations

Country	Name	City	State
Brazil	Laboratory on Clinical research on AIDS-INI FIOCRUZ	Rio De Janeiro
Cambodia	National Center for HIV/AIDS, Dermatology and STD (NCHADS)	Phnom Penh
Cameroon	Yaoundé Central Hospital	Yaoundé
Côte D'Ivoire	SMIT CHU de Treichville, CEPREF, CNTS	Abidjan
France	Service de Maladies Infectieuses et Tropicales AP-HP Hôpital Saint-Louis-Lariboisière	Paris
Mozambique	Centro de Saúde 1o de Maio	Maputo

Sponsors (2)

Lead Sponsor	Collaborator
ANRS, Emerging Infectious Diseases	MSD France

Countries where clinical trial is conducted

Brazil,  Cambodia,  Cameroon,  Côte D'Ivoire,  France,  Mozambique, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-inferiority of doravirine in combination with tenofovir and lamivudine as compared to dolutegravir in combination with tenofovir and lamivudine or emtricitabine	The non-inferiority will be assessed in terms of virologic efficacy at week 48, measured by the proportion of subjects achieving a rate of 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.; The rate of HIV 1 RNA will be measured by RT-PCR.	Week 48