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| Name | Class |
|---|---|
| MSD France | INDUSTRY |
| European and Developing Countries Clinical Trials Partnership (EDCTP) | OTHER_GOV |
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Phase III trial evaluating doravirine as an alternative to dolutegravir in treatment naïve people living with HIV-1 infection.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Doravirine arm | Experimental | Doravirine (100 mg) + tenofovir DF (300 mg) + lamivudine (300mg) administered daily |
|
| Dolutegravir arm | Active Comparator | Dolutegravir (50 mg) + tenofovir DF 300 mg + XTC (300 mg if lamivudine or 200 mg if emtricitabine) administered daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doravirine + tenofovir DF + lamivudine | Drug | Oral administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | The non-inferiority will be assessed in terms of virologic efficacy at week 48 under allocated treatment using the FDA snapshot algorithm (window period of 42-54 weeks), and 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of obesity | Obesity will be defined as having BMI≥30 kg/m² for Caucasian and African population and BMI≥27.5 kg/m² for Asian populations. | Week 48; Week 96 |
| Occurrence of insulin resistance |
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Inclusion Criteria:
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:
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
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anthony L'HOSTELLIER | Contact | 33 (0)5 57 57 47 11 | anthony.lhostellier@u-bordeaux.fr | |
| Olivier MARCY, Dr | Contact | 33 (0)5 57 57 13 93 | olivier.marcy@u-bordeaux.fr |
| Name | Affiliation | Role |
|---|---|---|
| Pierre SELLIER, Dr | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Beatriz GRINSZTEJN, Pr | INI-FIOCRUZ | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Geral de Nova Iguaçu | Recruiting | Nova Iguaçu | Rio de Janeiro | 26030-380 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41644158 | Derived | 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 with HIV-1 (ANRS0392s ELDORADO): protocol for an international, open-label, randomised, non-inferiority, phase III trial. BMJ Open. 2026 Feb 5;16(2):e110560. doi: 10.1136/bmjopen-2025-110560. |
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| Dolutegravir + tenofovir DF + lamivudine or emtricitabine | Drug | Oral administration |
|
Proportion of subjects with newly measured HOMA≥2 as compared to baseline HOMA will be calculated with the following formula (glucose levels in mmol/L, insulin levels in mIU/L): HOMA =(glucose ×insulin)÷22.5
| Week 48; Week 96 |
| Occurrence of hypertension | Proportion of subjects with hypertension newly detected compared to baseline. Hypertension will be defined as either being prescribed new anti-hypertension medication and/or by having diastolic blood pressure >90 mmHg AND/OR systolic blood pressure >140 mmHg during visit and confirmed during subsequent visit > 15 days after. | 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 | Proportion of subjects in virologic success defined as achieving HIV-1 RNA <50 copies/mL at week 96 under allocated treatment using the FDA snapshot algorithm with a window period of 90 to 102 weeks; subjects not achieving viral success will be described according to the FDA snapshot recommendation | Week 96 |
| Occurrence of virological failures | Proportion of confirmed virological failures. Virological failure will be defined as 1) confirmed HIV-1 RNA ≥ 200 copies/mL after initial response with HIV-1 RNA < 50 copies/mL at any time during the study or 2) non-response defined as either confirmed HIV-1 RNA ≥ 200 copies/mL at Week 24 or Week 36 (or any other unscheduled visit in-between) or confirmed HIV-1 RNA ≥ 50 copies/mL at Week 48, Week 72 and Week 96 (or any other unscheduled visit in-between). | Virological failure |
| Occurrence of HIV-1 drug resistances in patients with confirmed virological failure | Frequency of HIV-1 drug resistances in participants with a confirmed virological failure. Drug resistances will be defined according to the last version of the ANRS algorithm and to the last version of the Stanford algorithm. | Virological Failure |
| Virological efficacy at a threshold of HIV 1 RNA<200 copies/mL | Proportion of subjects achieving HIV 1 RNA<200 copies/mL under allocated treatment | Week 48; Week 96 |
| Virological efficacy at a threshold of HIV 1 RNA<1000 copies/mL | Proportion of subjects achieving HIV 1 RNA<1000 copies/mL under allocated treatment | Week 48; Week 96 |
| Effect of baseline RT and integrase mutations on virological response | Frequency of RT and integrase mutations at baseline and impact on the virological response | Week 48; Week 96 |
| Occurrence of combined overweight and obesity | Combined overweight and obesity will be defined as having BMI≥25 kg/m² for Caucasian and African populations and BMI≥23 kg/m² for Asian populations | Week 48; Week 96 |
| Occurrence of weight gain ≥10% absolute body weight | Proportion of subjects with ≥10% absolute weight gain from baseline | Week 48; Week 96 |
| Changes in absolute weight gain | Absolute weight gain will be calculated by simply subtracting the follow-up weight from baseline weight measured according to protocol procedures | Week 48; Week 96 |
| Occurrence of diabetes | Proportion of subjects with diabetes newly detected compared to baseline. Diabetes will be defined as either being prescribed new medication for diabetes mellitus and/or having a fasting glycemia ≥1.26 g/L during visit and confirmed during subsequent visit > 15 days after and/or in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dL (11.1 mmol/L). | Week 48; Week 96 |
| Safety and tolerability | Any adverse event of any grade and those graded 3-4 | Week 48; Week 96 |
| Changes in waist circumference, hip circumference and waist-to-hip ratio | Change from baseline in waist and hip circumferences and waist-to-hip ratio | Week 48; Week 96 |
| Changes in fasting glycemia and insulin | Change from baseline in fasting glycemia and insulin | Week 48; Week 96 |
| Changes in fasting serum lipids | Change from baseline in fasting serum lipids. The fasting serum lipids analyzed will be total cholesterol, HDL, LDL and triglycerides. | Week 48; Week 96 |
| Changes in estimated glomerular filtration rate | Change from baseline in estimated glomerular filtration rate. Estimated glomerular filtration rate (eGFR) will be calculated using the CKD-EPI equation | Week 48; Week 96 |
| Occurrence of cardiovascular abnormalities | Change from baseline in cardiovascular parameters (blood pressure profile, electrocardiographic and echocardiographic damages). These cardiovascular parameters assessments will be measured through an electrocardiogram, a transthoracic echocardiography and an ABPM, a 24-hour blood pressure Holter. | Week 48; Week 96 |
| Changes in liver steatosis and clinically significant fibrosis | Change from baseline in mean patient CAP and LSM measurements and occurrence of: Liver steatosis defined by CAP ≥ 263 dB/m2, and clinically significant liver fibrosis and cirrhosis defined by LSM ≥ 8.0 kPa and LSM ≥ 12.5 kPa, respectively | Week 48; Week 96 |
| Occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic-associated steatohepatitis (MASH) | Change from baseline in mean patient CAP and LSM measurements and occurrence of: MASLD defined by the presence of liver steatosis with at least one cardiometabolic risk-factor (overweight/obesity; pre-or diabetes; hypertension; hypertriglyceridemia or low-HDL; and MASH defined by the presence of at least CSF in people with MASLD. | Week 48; Week 96 |
| Changes in liver diseases biomarkers | Changes from baseline in Fib-4, VCTE and FAST scores and presence at baseline or occurrence of: CSF defined as Fib-4 ≥ 2.67 and FAST score > 0.67 (high probability of MASH) | Week 48; Week 96 |
| Changes in mental health and quality of life outcomes | Change from baseline in EQ-5D-3L, HIVTSQ, DASS-21, PSQI, WHOQOL HIV-BREF scores | Week 24; Week 48; Week 96 |
| Occurrence of Acquired Immune Deficiency Syndrome (AIDS), tuberculosis, Immune Reconstitution Inflammatory Syndrome (IRIS) or death | Proportion of subjects with AIDS (defined as having CDC stage 3/C or WHO stage 4), tuberculosis, IRIS or death | Week 48; Week 96 |
| Description of antiretroviral drugs trough plasma concentration in each arm | DOR, DTG and M9 trough plasma concentration in samples taken pre-dose | Week 4; Week 24; Week 48; Week 96 |
| Assessment of the effect of antiretroviral drugs trough plasma concentration on virological response | DOR, DTG and M9 trough plasma concentration in samples taken pre-dose | Week 4; Week 24; Week 48; Week 96 |
| Determining DOR, DTG and M9 trough plasma concentration thresholds predictive of virological response | DOR, DTG and M9 trough plasma concentration in samples taken pre-dose | Week 4; Week 24; Week 48; Week 96 |
| Assessment of the effect of antiretroviral drugs trough plasma concentration on safety endpoints | DOR, DTG and M9 trough plasma concentration in samples taken pre-dose | Week 4; Week 24; Week 48; Week 96 |
| Changes in CD4 cell count, CD4 percentage, CD8 cell count, CD8 percentage, CD4/CD8 ratio | Change from baseline in CD4 cell count, CD4 percentage, CD8 cell count, CD8 percentage, CD4/CD8 ratio | Week 48; Week 96 |
| Adherence to ART | Adherence to ART by (1) pill count (considering a pill count adherence ratio <95% as sub-optimal adherence), (2) 4-days and 1-month recall questions at every trial visit, (3) by TFV-DP quantification in dried blood spots (LC/MS). ARV pill burden will also be an endpoint in order to study the relation between adherence and ARV pill burden. | Week 48; Week 96 |
| Description of the distribution of CYP3A5/4 mutations according to ARV regimen | Type and frequency of alleles variants in the gene coding for CYP3A5/4 | Study long |
| Assessment of the impact of CYP3A5/4 mutations on PK | Impact of CYP3A5/4 mutations on pharmacokinetics of DOR, DTG and M9 | Study long |
| Assessment of the impact of CYP3A5/4 mutations on virological response and side effects | Virological response and side-effects depending on CYP3A5/4 mutations | Study long |
| Explore additional polymorphism (i.e. UGT1A1) according to literature update | Assess additional polymorphism of UGT1A1 | Baseline |
| Cost-effectiveness and budget impact of using DOR-based versus DTG-based antiretroviral regimens | Cost-effectiveness measured by (1) Incremental health benefits of using one regimen compared to the other (in DALYs and QALYs), (2) Incremental economic costs of using one regimen compared to the other (USD), (3) Budget impact of changing from one regimen to the other (USD) | Study long |
| Changes in truncal fat distribution in a sub-group of cisgender women enrolled in the trial | Change from baseline in truncal fat distribution. Truncal fat repartition will be measured by the proportion of fat tissue using DEXA-scanner assessment | Week 48; Week 96 |
| Changes in adipose tissue markers and immune activation markers in a sub-group of cisgender women enrolled in the trial | Change from baseline in adipose tissue markers (adiponectin, leptin) and immune activation markers (sCD14, sCD163). Measurement will be made on stored serum samples by immunonephelometry or ELISA. | Week 48; Week 96 |
| Changes in fat quality in a sub-group of cisgender women enrolled in the trial | Change from baseline (by abdominal subcutaneous surgical biopsy) in fat pathology, gene expression and global transcriptome analysis (RT-PCR and RNAseq). Measurement will be made on an abdominal fat tissue biopsy sample fixed for immunohistochemistry (Red Sirius, collagen 6, fibronectine, TFG-beta, alpha-SMA) and frozen for gene expression analysis by RT-PCR of markers of adipogenesis (PPARG, CEPBA), beiging (PRDM16, PGC1A), lipogenesis (FAS), adipocyte function (GLUT4), fibrosis (COL4, COL6, FN, TGFB, LOX, ASMA) and mDNA level (mDNA gene and nDNA). | Week 48 |
| Laboratory on Clinical research on AIDS-INI FIOCRUZ | Recruiting | Rio de Janeiro | Rio de Janeiro | 21040-900 | Brazil |
|
| Hôpital Central de Yaoundé | Recruiting | Yaoundé | Cameroon |
|
| Centre de prise en charge de Recherche et de Formation (CEPREF) | Not yet recruiting | Abidjan | Côte d’Ivoire |
|
| Centre Médical de Suivi des Donneurs de Sang (CMSDS) - Centre National de Transfusion Sanguine (CNTS) | Not yet recruiting | Abidjan | Côte d’Ivoire |
|
| CHU de Treichville, Service des Maladies Infectieuses et Tropicales (SMIT) | Recruiting | Abidjan | Côte d’Ivoire |
|
| CHU Bordeaux Pellegrin - Service des Maladies Infectieuses et Tropicales | Recruiting | Bordeaux | 33075 | France |
|
| CHU Bordeaux St André - Service de Médecine Interne | Recruiting | Bordeaux | 33075 | France |
|
| CHU Montpellier - Hôpital La Colombière - Service des Maladies Infectieuses et Tropicales | Recruiting | Montpellier | 34295 | France |
|
| CHU Nantes Hôtel Dieu - Service des Maladies infectieuses et tropicales | Recruiting | Nantes | 44093 | France |
|
| AP-HP Hôpital Lariboisière - Service de Maladies Infectieuses et Tropicales | Recruiting | Paris | 75010 | France |
|
| AP-HP Hôpital Saint Louis - Service des Maladies Infectieuses et Tropicales | Recruiting | Paris | 75010 | France |
|
| AP-HP Hôpital Saint Antoine - Service des Maladies Infectieuses et Tropicales | Recruiting | Paris | 75012 | France |
|
| AP-HP Hôpital Pitié Salpêtrière - Service des Maladies Infectieuses et Tropicales | Recruiting | Paris | 75013 | France |
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| AP-HP Bichat Claude Bernard - Service des Maladies Infectieuses et Tropicales | Recruiting | Paris | 75018 | France |
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| Centro de Saúde 1o de Maio | Recruiting | Maputo | Mozambique |
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| Chiangrai Prachanukroh | Not yet recruiting | Chiang Rai | 57000 | Thailand |
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| Lampang Hospital Internal Medicine department | Not yet recruiting | Lampang | 52000 | Thailand |
|
| Phayao Hospital Internal Medicine department | Not yet recruiting | Phayao | 56000 | Thailand |
|
| ID | Term |
|---|---|
| C000592662 | doravirine |
| D000068698 | Tenofovir |
| D019259 | Lamivudine |
| C562325 | dolutegravir |
| D000068679 | Emtricitabine |
| ID | Term |
|---|---|
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D000225 | Adenine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D016047 | Zalcitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D015224 | Dideoxynucleosides |
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