Clinical trial • Phase III • Infectious Disease

DORAVIRINE for HIV infection

Phase III trial of DORAVIRINE for HIV infection.

Overview

Trial Therapeutic Area
Infectious Disease
Trial Disease
HIV infection
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
17-09-2024
First CTIS Authorization Date
07-01-2025

Trial design

Dolutegravir + lamivudine (DTG/3TC) (comparator arm: dolutegravir/lamivudine). Dose and schedule not specified in the provided record.-controlled Phase III trial across 37 sites in France.

Comparator
Dolutegravir + lamivudine (DTG/3TC) (comparator arm: dolutegravir/lamivudine). Dose and schedule not specified in the provided record.
Target Sample Size
408
Trial Duration For Participant
672

Eligibility

Recruits 408 No vulnerable populations selected. Only adults (≥18 years) are eligible. Written informed consent is required from participants. No assent or parental consent arrangements are described for minors (minors are excluded). Subject information and informed consent forms for adults are provided in the application documents..

Pregnancy Exclusion
• Pregnant or breastfeeding women, and women with age to be pregnant but refusing contraception;
Vulnerable Population
No vulnerable populations selected. Only adults (≥18 years) are eligible. Written informed consent is required from participants. No assent or parental consent arrangements are described for minors (minors are excluded). Subject information and informed consent forms for adults are provided in the application documents.

Inclusion criteria

  • {"criterion_text":"- •\tAdults ≥18 years;\n- •\tLiving with HIV-1;\n- •\tWith pVL <50 copies/mL for at least 24 months;\n- •\tUnder stable (7 days/7, 5 days/7 or 4 days/7) three-drug regimen including 2 NRTIs + 1 NNRTI or 1 INSTI or 1 boosted PI for at least 6 months;\n- •\tAffiliated to the French Social Insurance;\n- •\tWho have given their written consent to participate in the study.\n- •\tPatients with a DNA genotype in which the integrase gene could not be amplified, -\tAnd who have never been exposed to integrase inhibitors, -\tOr who have previously been exposed to integrase inhibitors, but without a history of virological failure;"}

Exclusion criteria

  • {"criterion_text":"- •\tHIV-2 co-infection;\n- •\tCo-infection with hepatitis B virus (positive HBsAg and/or positive anti-HBc antibody with negative anti-HBs antibody);\n- •\tDocumented resistance mutation or association of resistance mutations, associated with partial or full resistance to doravirine, dolutegravir or lamivudine, using the last version of the ANRS-MIE algorithm;\n- •\tAt least one resistance genotype is mandatory to include the patient: o\tIf there was no virological failure under NRTI, NNRTI and INSTI in the past: -\tPretherapeutic HIV-RNA genotype, -\tOR, in case of no available HIV-RNA genotype, genotype on proviral HIV-DNA to performed before inclusion, o\tIn case of virological failure under NRTI, NNRTI and INSTI in the past: -\tHIV-RNA genotype at time of virological failure, -\tOR, in case of no available HIV-RNA genotype at time of failure, genotype on proviral HIV-DNA to performed before inclusion to be sure that the virus is fully sensitive to the study treatments, o\tPast virological failure is defined as: 2 consecutive pVL ≥50 copies/mL or one pVL ≥200 copies/mL, o\tResistance genotypes will be interpretated with the last available ANRS algorithm.;\n- •\tGlomerular filtration rate <50 mL/min (CKD-EPI formula);\n- •\tComedications leading to drug-drug interaction with one of the 3 study drugs (cf. detailed protocol);\n- •\tPregnant or breastfeeding women, and women with age to be pregnant but refusing contraception;\n- •\tAny clinal condition limiting the participation in a clinical trial."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Proportion of participants with virological failure at W48 (2 consecutive pVL >50 copies/mL with a delay of 2-4 weeks).","definition_or_measurement_approach":"Virological failure defined as 2 consecutive plasma viral loads (pVL) >50 copies/mL measured 2-4 weeks apart (or as per main objective: 2 consecutive pVL ≥50 copies/mL or one pVL ≥50 copies/mL followed by discontinuation). Assessed at Week 48."}

Secondary endpoints

  • {"endpoint_text":"- Proportion of participants with virological failure at W96;","definition_or_measurement_approach":"Proportion with virological failure at Week 96 using the same virological failure definition as primary endpoint."}
  • {"endpoint_text":"- Proportion of participants with discontinuation of treatment or follow-up over 96 weeks;","definition_or_measurement_approach":"Proportion of participants who discontinue study treatment or follow-up during the 96-week follow-up period."}
  • {"endpoint_text":"- Proportion of participants with new resistance associated mutations in case of virological failure;","definition_or_measurement_approach":"Assessment of emergence of resistance-associated mutations at the time of virological failure (genotypic resistance testing)."}
  • {"endpoint_text":"- Plasma drug concentrations at W24, W48, W72 and W96, and in case of virological failure;","definition_or_measurement_approach":"Measurement of residual plasma antiretroviral concentrations at Weeks 24, 48, 72 and 96 and at virological failure."}
  • {"endpoint_text":"- Proportion of participants with severe biological or clinical side effect over 96 weeks;","definition_or_measurement_approach":"Incidence of clinical or biological adverse events of grade 3 or higher over 96 weeks."}
  • {"endpoint_text":"- CD4 and CD8 T-cell counts, CD4/CD8 ratio at D0, W48 and W96;","definition_or_measurement_approach":"Laboratory measurement of CD4 and CD8 T-cell counts and CD4/CD8 ratio at baseline (D0), Week 48 and Week 96."}
  • {"endpoint_text":"- Body weight and BMI et IMC at D0, W48 and W96;","definition_or_measurement_approach":"Measurement of body weight and body mass index at baseline, Week 48 and Week 96."}
  • {"endpoint_text":"- Metabolic biomarkers (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glycemia) at D0, W48 and W96;","definition_or_measurement_approach":"Laboratory assessment of metabolic biomarkers at baseline, Week 48 and Week 96."}
  • {"endpoint_text":"- Levels of total HIV-DNA in PBMC at D0, W48 and W96;","definition_or_measurement_approach":"Quantification of total HIV-DNA in peripheral blood mononuclear cells at baseline, Week 48 and Week 96."}
  • {"endpoint_text":"- Proportion of participants with residual viremia at D0, W48 and W96;","definition_or_measurement_approach":"Proportion with residual viremia (pVL <20 copies/mL with detectable RT-PCR signal) at baseline, Week 48 and Week 96."}
  • {"endpoint_text":"- Levels of satisfaction associated with study treatments at D0, W48 and W96 (HIVTSQ questionnaire);","definition_or_measurement_approach":"Participant-reported treatment satisfaction measured by the HIVTSQ questionnaire at baseline, Week 48 and Week 96."}
  • {"endpoint_text":"- Drug concentrations in female genital secretion or semen at W24 and W48 (among participants of the “genital compartment” sub-study);","definition_or_measurement_approach":"Measurement of antiretroviral concentrations in genital secretions or semen at Weeks 24 and 48 for participants in the genital compartment sub-study."}
  • {"endpoint_text":"- Levels of HIV-RNA in female genital secretion or semen at W24 and W48 (among participants of the “genital compartment” sub-study).","definition_or_measurement_approach":"Measurement of HIV-RNA levels in genital secretions or semen at Weeks 24 and 48 for participants in the genital compartment sub-study."}

Recruitment

Planned Sample Size
408
Recruitment Window Months
42
Consent Approach
Written informed consent required: participants 'Who have given their written consent to participate in the study.' Consent documents for adults (L1_SIS and ICF_adults and variants) are included in the application. Only adults (≥18 years) are eligible; no assent/parental consent procedures described.

Geography

Total Number Of Sites
37
Total Number Of Participants
408

France

Earliest CTIS Part Ii Submission Date
12-12-2024
Latest Decision Or Authorization Date
12-05-2026
Processing Time Days
516
Number Of Sites
37
Number Of Participants
408

Sites

Site Name
Centre Hospitalier Departemental Vendee
Department Name
Post Emergencies Medicine and infectious diseases
Principal Investigator Name
Olivier BOLLENGIER STRAGIER
Principal Investigator Email
olivier.bollengier-stragier@ght85.fr5.fr
Contact Person Name
Olivier BOLLENGIER STRAGIER
Site Name
Centre Hospitalier Universitaire Hôtel-Dieu
Department Name
Diagnostic and therapeutic centre
Principal Investigator Name
Jean-Paul VIARD
Principal Investigator Email
Jean-paul.viard@aphp.fr
Contact Person Name
Jean-Paul VIARD
Contact Person Email
Jean-paul.viard@aphp.fr
Site Name
Hôpital Avicenne
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Hugues CORDEL MACAUX
Principal Investigator Email
hugues.cordel@aphp.fr
Contact Person Name
Hugues CORDEL MACAUX
Contact Person Email
hugues.cordel@aphp.fr
Site Name
Hopitaux Universitaires Pitie Salpetriere
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Romain PALICH
Principal Investigator Email
romain.palich@aphp.fr
Contact Person Name
Romain PALICH
Contact Person Email
romain.palich@aphp.fr
Site Name
Hopital Bichat - Claude Bernard
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Jade GHOSN
Principal Investigator Email
jade.ghosn@aphp.fr
Contact Person Name
Jade GHOSN
Contact Person Email
jade.ghosn@aphp.fr
Site Name
Centre Hospitalier Et Universitaire De Limoges
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Claire GENET
Principal Investigator Email
claire.genet@chu-limoges.fr
Contact Person Name
Claire GENET
Contact Person Email
claire.genet@chu-limoges.fr
Site Name
Centre Hospitalier Universitaire D'Angers
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Pascale FIALAIRE
Principal Investigator Email
pafialaire@chu-angers.fr
Contact Person Name
Pascale FIALAIRE
Contact Person Email
pafialaire@chu-angers.fr
Site Name
Centre Hospitalier General De St Denis
Department Name
Infectious diseases
Principal Investigator Name
Marie-Aude KHUONG-JOSSE
Principal Investigator Email
marieaude.khuong@ch-stdenis.fr
Contact Person Name
Marie-Aude KHUONG-JOSSE
Contact Person Email
marieaude.khuong@ch-stdenis.fr
Site Name
Centre Hospitalier Intercommunal De Cornouaille
Department Name
Infectious Diseases
Principal Investigator Name
Nolwenn HALL
Principal Investigator Email
nolwenn.hall@ch-cornouaille.fr
Contact Person Name
Nolwenn HALL
Contact Person Email
nolwenn.hall@ch-cornouaille.fr
Site Name
Hôpital Raymond-Poincaré
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Pierre de TRUCHIS
Principal Investigator Email
p.de-truchis@aphp.fr
Contact Person Name
Pierre de TRUCHIS
Contact Person Email
p.de-truchis@aphp.fr
Site Name
Hopital Ambroise Pare
Department Name
Infectious diseases
Principal Investigator Name
Pierre de TRUCHIS
Principal Investigator Email
p.de-truchis@aphp.fr
Contact Person Name
Pierre de TRUCHIS
Contact Person Email
p.de-truchis@aphp.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Pierre DELOBEL
Principal Investigator Email
delobel.p@chu-toulouse.fr
Contact Person Name
Pierre DELOBEL
Contact Person Email
delobel.p@chu-toulouse.fr
Site Name
Hopital Saint Antoine
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Karine LACOMBE
Principal Investigator Email
karine.lacombe2@aphp.fr
Contact Person Name
Karine LACOMBE
Contact Person Email
karine.lacombe2@aphp.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Alain MAKINSON
Principal Investigator Email
a-makinson@chu-montpellier.fr
Contact Person Name
Alain MAKINSON
Contact Person Email
a-makinson@chu-montpellier.fr
Site Name
Centre Hospitalier Universitaire De Nice
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
David CHIRIO
Principal Investigator Email
chirio.d@chu-nice.fr
Contact Person Name
David CHIRIO
Contact Person Email
chirio.d@chu-nice.fr
Site Name
Centre Hospitalier Universitaire De Saint Etienne
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Amandine GAGNEUX-BRUNON
Principal Investigator Email
amandine.gagneux-brunon@chu-st-etienne.fr
Contact Person Name
Amandine GAGNEUX-BRUNON
Site Name
Hopital Antoine-Beclere
Department Name
Internal Medicine
Principal Investigator Name
Sophie ABGRALL
Principal Investigator Email
sophie.abgrall@aphp.fr
Contact Person Name
Sophie ABGRALL
Contact Person Email
sophie.abgrall@aphp.fr
Site Name
Hôpital Lariboisière - APHP
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Agathe Rami
Principal Investigator Email
agathe.rami@aphp.fr
Contact Person Name
Agathe Rami
Contact Person Email
agathe.rami@aphp.fr
Site Name
Hopital Tenon
Department Name
Infectious Diseases
Principal Investigator Name
Gilles PIALOUX
Principal Investigator Email
gilles.pialoux@aphp.fr
Contact Person Name
Gilles PIALOUX
Contact Person Email
gilles.pialoux@aphp.fr
Site Name
Nouvel Hopital Civil Strasbourg
Department Name
Internal Medicine
Principal Investigator Name
Axel URSENBACH
Principal Investigator Email
axel.ursenbach@chu-strasbourg.fr
Contact Person Name
Axel URSENBACH
Site Name
Hopital Necker Enfants Malades
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Claudine DUVIVIER
Principal Investigator Email
claudine.duvivier@aphp.fr
Contact Person Name
Claudine DUVIVIER
Contact Person Email
claudine.duvivier@aphp.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Fabrice BONNET
Principal Investigator Email
Fabrice.bonnet@chu-bordeaux.fr
Contact Person Name
Fabrice BONNET
Contact Person Email
Fabrice.bonnet@chu-bordeaux.fr
Site Name
Centre Hospitalier Universitaire Reims
Department Name
Internal Medicine, Infectious and Tropical Diseases and Clinical immunology
Principal Investigator Name
Firouze BANI-SADR
Principal Investigator Email
fbanisadr@chu-reims.fr
Contact Person Name
Firouze BANI-SADR
Contact Person Email
fbanisadr@chu-reims.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Clotilde ALLAVENA
Principal Investigator Email
clotilde.allavena@chu-nantes.fr
Contact Person Name
Clotilde ALLAVENA
Site Name
Centre Hospitalier De Tourcoing
Department Name
University of Infectious and Traveller Diseases
Principal Investigator Name
Olivier ROBINEAU
Principal Investigator Email
orobineau@ch-tourcoing.fr
Contact Person Name
Olivier ROBINEAU
Contact Person Email
orobineau@ch-tourcoing.fr
Site Name
Centre Hospitalier Universitaire de la Guadeloupe
Department Name
Ambulatory Medicine Platform
Principal Investigator Name
Antoine CHERET
Principal Investigator Email
antoine.cheret@aphp.fr
Contact Person Name
Antoine CHERET
Contact Person Email
antoine.cheret@aphp.fr
Site Name
CHU De Martinique
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
André CABIE
Principal Investigator Email
andre.cabie@chu-martinique.fr
Contact Person Name
André CABIE
Contact Person Email
andre.cabie@chu-martinique.fr
Site Name
Hopital Saint Louis
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Nathalie DE CASTRO
Principal Investigator Email
nathalie.de-castro@aphp.fr
Contact Person Name
Nathalie DE CASTRO
Contact Person Email
nathalie.de-castro@aphp.fr
Site Name
Centre Hospitalier Victor Dupouy
Department Name
Immuno-Hématologie, Unité VIH-IST
Principal Investigator Name
Fabienne CABY
Principal Investigator Email
fabienne.caby@ch-argenteuil.fr
Contact Person Name
Fabienne CABY
Contact Person Email
fabienne.caby@ch-argenteuil.fr
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Infectious Diseases
Principal Investigator Name
Lionel PIROTH
Principal Investigator Email
Lionel.piroth@chu-dijon.fr
Contact Person Name
Lionel PIROTH
Contact Person Email
Lionel.piroth@chu-dijon.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Charles CAZANAVE
Principal Investigator Email
charles.cazanave@chu-bordeaux.fr
Contact Person Name
Charles CAZANAVE
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Clinical immuno-hematology
Principal Investigator Name
Olivia ZAEGEL-FAUCHER
Principal Investigator Email
olivia.zaegel@ap-hm.fr
Contact Person Name
Olivia ZAEGEL-FAUCHER
Contact Person Email
olivia.zaegel@ap-hm.fr
Site Name
Centre Hospitalier Universitaire de Clermont-Ferrand - Hôpital Gabriel Montpied
Department Name
Infectious Diseases
Principal Investigator Name
Florence ANGLADE
Principal Investigator Email
fanglade@chu-clermontferrand.fr
Contact Person Name
Florence ANGLADE
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Infectious Diseases
Principal Investigator Name
Lea PICARD
Principal Investigator Email
lea.picard@chu-rennes.fr
Contact Person Name
Lea PICARD
Contact Person Email
lea.picard@chu-rennes.fr
Site Name
Centre Hospitalier Intercommunal de Villeneuve Saint Georges
Department Name
Infectious diseases
Principal Investigator Name
Pauline CARAUX-PAZ
Principal Investigator Email
pauline.caraux-paz@chiv.fr
Contact Person Name
Pauline CARAUX-PAZ
Contact Person Email
pauline.caraux-paz@chiv.fr
Site Name
Centre Hospitalier Universitaire D Orleans
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Laurent HOCQUELOUX
Principal Investigator Email
Laurent.hocqueloux@chu-orleans.fr
Contact Person Name
Laurent HOCQUELOUX
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Infectious and Tropical Diseases
Principal Investigator Name
Amélie MENARD
Principal Investigator Email
amelie.menard@ap-hm.fr
Contact Person Name
Amélie MENARD
Contact Person Email
amelie.menard@ap-hm.fr

Sponsor

Primary sponsor

Full Name
Centre De Recherches Et D'Etudes Sur La Pathologie Tropicale Et Le Sida
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Third parties

  • {"country":"","full_name":"Agence Nationale de Recherche sur les hépatites, le VIH/SIDA et les Maladies Infectieuses Emergentes","duties_or_roles":"Monetary support / funding","organisation_type":""}

Co-sponsors

  • ANRS Maladies Infectieuses Emergentes

Investigational products

Investigational Product Name
DORAVIRINE
Active Substance
DORAVIRINE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
100 mg
Investigational Product Name
LAMIVUDINE
Active Substance
LAMIVUDINE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
300 mg
Investigational Product Name
LAMIVUDINE AND DOLUTEGRAVIR
Active Substance
LAMIVUDINE, DOLUTEGRAVIR
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Combination Treatment
Yes

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