Clinical trial • Phase III • Infectious Disease
Doravirine; Islatravir for HIV-1 infection
Phase III trial of Doravirine; Islatravir for HIV-1 infection.
Overview
- Trial Therapeutic Area
- Infectious Disease
- Trial Disease
- HIV-1 infection
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 04-12-2023
- First CTIS Authorization Date
- 25-03-2024
Trial design
Randomised, two randomized treatment groups: dor/isl (doravirine/islatravir) 100 mg/0.25 mg once-daily (taken with matching placebo to bic/ftc/taf) versus biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) 50 mg/200 mg/25 mg film-coated tablet once-daily (taken with matching placebo to dor/isl).-controlled Phase III trial in Germany, France, Spain.
- Randomised
- Yes
- Comparator
- Two randomized treatment groups: DOR/ISL (Doravirine/Islatravir) 100 mg/0.25 mg once-daily (taken with matching placebo to BIC/FTC/TAF) versus Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) 50 mg/200 mg/25 mg film-coated tablet once-daily (taken with matching placebo to DOR/ISL).
- Target Sample Size
- 560
- Trial Duration For Participant
- 1008
Eligibility
Recruits 560 Vulnerable populations not selected (isVulnerablePopulationSelected: false). Informed consent is by the adult participant (≥18). Subject information and informed consent forms are provided (multiple language and country-specific versions listed), and additional optional consent forms/addenda exist (e.g. FBR consent, optional infant follow-up, optional treatment during pregnancy, optional extension period) as separate documents..
- Pregnancy Exclusion
- Female is not a participant of childbearing potential (POCBP); or if a POCBP, is not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration
- Vulnerable Population
- Vulnerable populations not selected (isVulnerablePopulationSelected: false). Informed consent is by the adult participant (≥18). Subject information and informed consent forms are provided (multiple language and country-specific versions listed), and additional optional consent forms/addenda exist (e.g. FBR consent, optional infant follow-up, optional treatment during pregnancy, optional extension period) as separate documents.
Inclusion criteria
- {"criterion_text":"- Is an individual ≥18 years of age of any sex/gender who is HIV-1 positive with plasma HIV-1 RNA ≥500 copies/mL at screening"}
- {"criterion_text":"- Is naïve to antiretroviral therapy (ART) defined as having received no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection"}
- {"criterion_text":"- Female is not a participant of childbearing potential (POCBP); or if a POCBP, is not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration"}
Exclusion criteria
- {"criterion_text":"- Has HIV-2 infection"}
- {"criterion_text":"- Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator"}
- {"criterion_text":"- Has a diagnosis of an active AIDS-defining opportunistic infection within 30 days prior to screening"}
- {"criterion_text":"- Has active hepatitis B infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA]-positive)."}
- {"criterion_text":"- Has chronic hepatitis C virus (HCV) infection (detectable HCV ribonucleic acid [RNA])"}
- {"criterion_text":"- Has a history of malignancy ≤5 years prior to providing documented informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi’s sarcoma"}
- {"criterion_text":"- Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality, or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) ≥50 copies/mL at Week 48","definition_or_measurement_approach":"Measured as the percentage of participants with plasma HIV-1 RNA ≥50 copies/mL at Week 48 (plasma HIV-1 RNA assay at Week 48)."}
- {"endpoint_text":"- Percentage of participants experiencing ≥1 adverse event (AE) through Week 48","definition_or_measurement_approach":"Measured as the percentage of participants with at least one adverse event recorded/reported up to Week 48 (safety reporting through Week 48)."}
- {"endpoint_text":"- Percentage of participants discontinuing from study treatment due to an AE through Week 48","definition_or_measurement_approach":"Measured as the percentage of participants who discontinue study treatment because of an adverse event up to Week 48."}
Secondary endpoints
- {"endpoint_text":"- Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96","definition_or_measurement_approach":"Measured as percentage with plasma HIV-1 RNA <50 copies/mL at Week 96."}
- {"endpoint_text":"- Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48","definition_or_measurement_approach":"Measured as percentage with plasma HIV-1 RNA <200 copies/mL at Week 48."}
- {"endpoint_text":"- Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96","definition_or_measurement_approach":"Measured as percentage with plasma HIV-1 RNA <200 copies/mL at Week 96."}
- {"endpoint_text":"- Change from baseline in cluster of differentiation 4+ (CD4+) T-cells at Week 48","definition_or_measurement_approach":"Mean change from baseline in CD4+ T-cell count at Week 48 (laboratory immunologic assessment)."}
- {"endpoint_text":"- Change from baseline in CD4+ T-cells at Week 96","definition_or_measurement_approach":"Mean change from baseline in CD4+ T-cell count at Week 96."}
- {"endpoint_text":"- Incidence of viral drug resistance","definition_or_measurement_approach":"Assessed by detection of resistance-associated mutations/virologic analyses in participants who experience virologic failure."}
- {"endpoint_text":"- Change from baseline in body weight at Week 48","definition_or_measurement_approach":"Mean change from baseline in body weight at Week 48."}
- {"endpoint_text":"- Change from baseline in body weight at Week 96","definition_or_measurement_approach":"Mean change from baseline in body weight at Week 96."}
- {"endpoint_text":"- Percentage of participants experiencing ≥1 AE through Week 96","definition_or_measurement_approach":"Percentage of participants with at least one adverse event reported up to Week 96."}
- {"endpoint_text":"- Percentage of participants discontinuing from study treatment due to an AE through Week 48","definition_or_measurement_approach":"Percentage of participants who discontinue study treatment due to an adverse event through Week 48."}
- {"endpoint_text":"- Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144","definition_or_measurement_approach":"Percentage with plasma HIV-1 RNA <50 copies/mL at Week 144."}
- {"endpoint_text":"- Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144.","definition_or_measurement_approach":"Percentage with plasma HIV-1 RNA <200 copies/mL at Week 144."}
- {"endpoint_text":"- Change from baseline in CD4+ T-cells at Week 144.","definition_or_measurement_approach":"Mean change from baseline in CD4+ T-cell count at Week 144."}
- {"endpoint_text":"- Change from baseline in body weight at Week 144","definition_or_measurement_approach":"Mean change from baseline in body weight at Week 144."}
Recruitment
- Planned Sample Size
- 560
- Recruitment Window Months
- 65
- Consent Approach
- Informed consent is provided by adult participants (study includes individuals ≥18 years). Main subject information and informed consent forms are available as documents (country/language-specific versions listed for DEU, FRA, ESP and English versions), plus optional/ancillary consent forms (FBR consent, optional infant follow-up, optional treatment during pregnancy, optional extension period).
Methods
- K2_Recruitment Doc Patient Brochure (country-specific versions listed) — printed brochure materials targeted at potential participants (documents present for DEU, FRA, ESP).
- K2_Recruitment Doc Patient Flyer (country-specific versions) — flyers for potential participants (DEU, FRA, ESP).
- K2_Recruitment Doc Poster (country-specific versions) — posters for participant recruitment (DEU, FRA, ESP).
- K2_Recruitment Doc Advertisement (DEU) — recruitment advertisement document for Germany.
- K2_Recruitment HCP Reference Cards and HCP Fact Sheet (ESP) — materials aimed at healthcare professionals to support recruitment in Spain.
- K2_Recruitment Visit Calendar (ESP) — scheduling/visit calendar provided as recruitment material in Spain.
- HCP-targeted materials (reference cards, fact sheets) and patient-targeted printed materials provided in country-specific versions (Germany, France, Spain).
Geography
- Total Number Of Sites
- 23
- Total Number Of Participants
- 82
Germany
- Earliest CTIS Part Ii Submission Date
- 07-03-2024
- Latest Decision Or Authorization Date
- 26-03-2024
- Processing Time Days
- 19
- Number Of Sites
- 5
- Number Of Participants
- 17
Sites
- Site Name
- ICH Study Center GmbH & Co. KG
- Department Name
- ICH Study Center GmbH & Co. KG
- Principal Investigator Name
- Christian Hoffmann
- Principal Investigator Email
- hoffmann@ich-hamburg.de
- Contact Person Name
- Christian Hoffmann
- Contact Person Email
- hoffmann@ich-hamburg.de
- Site Name
- University Medical Center Hamburg-Eppendorf
- Department Name
- Bereich Infektiologie am Ambulanzzentrum Gebäude 028/EG/Raum 37
- Principal Investigator Name
- Olaf Degen
- Principal Investigator Email
- infektionen@uke.de
- Contact Person Name
- Olaf Degen
- Contact Person Email
- infektionen@uke.de
- Site Name
- Klinikum Der Universitat Munchen AöR
- Department Name
- Medizinische Klinik und Poliklinik IV Infektionsambulanz Poliklinik
- Principal Investigator Name
- Johannes Bogner
- Principal Investigator Email
- johannes.bogner@med.uni-muenchen.de
- Contact Person Name
- Johannes Bogner
- Contact Person Email
- johannes.bogner@med.uni-muenchen.de
- Site Name
- Universitaetsklinikum Bonn AöR
- Department Name
- Medizinische Klinik I - Klinisches Studienzentrum Immunologie
- Principal Investigator Name
- Jürgen Rockstroh
- Principal Investigator Email
- juergen.rockstroh@ukbonn.de
- Contact Person Name
- Jürgen Rockstroh
- Contact Person Email
- juergen.rockstroh@ukbonn.de
- Site Name
- Medical Center - University Of Freiburg
- Department Name
- HIV-Zentrum Abteilung Infektiologie
- Principal Investigator Name
- Matthias Müller
- Principal Investigator Email
- matthias.mueller@uniklinik-freiburg.de
- Contact Person Name
- Matthias Müller
- Contact Person Email
- matthias.mueller@uniklinik-freiburg.de
France
- Earliest CTIS Part Ii Submission Date
- 26-01-2024
- Latest Decision Or Authorization Date
- 25-03-2024
- Processing Time Days
- 59
- Number Of Sites
- 7
- Number Of Participants
- 26
Sites
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Hôpital Saint-Antoine _ Service des Maladies infectieuses et tropicales
- Principal Investigator Name
- Karine LACOMBE
- Principal Investigator Email
- karine.lacombe2@merck.com
- Contact Person Name
- Karine LACOMBE
- Contact Person Email
- karine.lacombe2@merck.com
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Hôpital Avicenne _ Service des Maladies infectieuses et tropicales
- Principal Investigator Name
- Nicolas VIGNIER
- Principal Investigator Email
- nicolas.vignier@aphp.fr
- Contact Person Name
- Nicolas VIGNIER
- Contact Person Email
- nicolas.vignier@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Hôpital Pitié Salpétrière _ Service des Maladies infectieuses et tropicales
- Principal Investigator Name
- Valerie POURCHER
- Principal Investigator Email
- valerie.martinez@aphp.fr
- Contact Person Name
- Valerie POURCHER
- Contact Person Email
- valerie.martinez@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Hôpital Saint Louis _ Service des Maladies infectieuses et tropicales
- Principal Investigator Name
- Jean-Michel MOLINA
- Principal Investigator Email
- jean-michel.molina@aphp.fr
- Contact Person Name
- Jean-Michel MOLINA
- Contact Person Email
- jean-michel.molina@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Hôpital Bichat _ Service des Maladies infectieuses et tropicales
- 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 De Tourcoing
- Department Name
- Service Universitaire des Maladies Infectieuses et du Voyageur
- 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 Nice
- Department Name
- Hôpital Archet _ Service des Maladies infectieuses et tropicales
- Principal Investigator Name
- Eric CUA
- Principal Investigator Email
- cua.e@chu-nice.fr
- Contact Person Name
- Eric CUA
- Contact Person Email
- cua.e@chu-nice.fr
Spain
- Earliest CTIS Part Ii Submission Date
- 10-01-2024
- Latest Decision Or Authorization Date
- 01-04-2024
- Processing Time Days
- 82
- Number Of Sites
- 11
- Number Of Participants
- 39
Sites
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Enfermedades Infecciosas
- Principal Investigator Name
- Jordi Navarro Mercade
- Principal Investigator Email
- jordi.navarro@vallhebron.cat
- Contact Person Name
- Jordi Navarro Mercade
- Contact Person Email
- jordi.navarro@vallhebron.cat
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Enfermedades Infecciosas
- Principal Investigator Name
- Leire Perez Latorre
- Principal Investigator Email
- legor78@hotmail.com
- Contact Person Name
- Leire Perez Latorre
- Contact Person Email
- legor78@hotmail.com
- Site Name
- Hospital Clinic De Barcelona
- Department Name
- Enfermedades Infecciosas
- Principal Investigator Name
- Josep Mallolas Masferrer
- Principal Investigator Email
- mallolas@clinic.cat
- Contact Person Name
- Josep Mallolas Masferrer
- Contact Person Email
- mallolas@clinic.cat
- Site Name
- Hospital Universitari Germans Trias I Pujol
- Department Name
- Enfermedades Infecciosas
- Principal Investigator Name
- Roger Paredes Deiros
- Principal Investigator Email
- rparedes@lluita.org
- Contact Person Name
- Roger Paredes Deiros
- Contact Person Email
- rparedes@lluita.org
- Site Name
- Hospital Universitario Virgen De La Victoria
- Department Name
- Enfermedades Infecciosas
- Principal Investigator Name
- Rosario Palacios Muñoz
- Principal Investigator Email
- rosariopalaci@gmail.com
- Contact Person Name
- Rosario Palacios Muñoz
- Contact Person Email
- rosariopalaci@gmail.com
- Site Name
- Hospital General Universitario De Elche
- Department Name
- Enfermedades Infecciosas
- Principal Investigator Name
- Félix Gutierrez Rodero
- Principal Investigator Email
- gutierrez_fel@gva.es
- Contact Person Name
- Félix Gutierrez Rodero
- Contact Person Email
- gutierrez_fel@gva.es
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Enfermedades Infecciosas
- Principal Investigator Name
- María de Lagarde Sebastián
- Principal Investigator Email
- maria.lagarde@salud.madrid.org
- Contact Person Name
- María de Lagarde Sebastián
- Contact Person Email
- maria.lagarde@salud.madrid.org
- Site Name
- Hospital Universitario Ramon Y Cajal
- Department Name
- Enfermedades Infecciosas
- Principal Investigator Name
- Santiago Moreno Guillen
- Principal Investigator Email
- smguillen@salud.madrid.org
- Contact Person Name
- Santiago Moreno Guillen
- Contact Person Email
- smguillen@salud.madrid.org
- Site Name
- Hospital Universitario La Paz
- Department Name
- Enfermedades Infecciosas
- Principal Investigator Name
- Rafael Mican Rivera
- Principal Investigator Email
- rafaele.mican@salud.madrid.org
- Contact Person Name
- Rafael Mican Rivera
- Contact Person Email
- rafaele.mican@salud.madrid.org
- Site Name
- Bellvitge University Hospital
- Department Name
- Enfermedades Infecciosas
- Principal Investigator Name
- Arkaitz Imaz Vacas
- Principal Investigator Email
- aimaz@bellvitgehospital.cat
- Contact Person Name
- Arkaitz Imaz Vacas
- Contact Person Email
- aimaz@bellvitgehospital.cat
- Site Name
- Hospital Universitario Fundacion Jimenez Diaz
- Department Name
- Enfermedades Infecciosas
- Principal Investigator Name
- Federico Pulido Ortega
- Principal Investigator Email
- fedepulido@gmail.com
- Contact Person Name
- Federico Pulido Ortega
- Contact Person Email
- fedepulido@gmail.com
Sponsor
Primary sponsor
- Full Name
- Merck Sharp & Dohme LLC
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Labcorp Central Laboratory Services S.a.r.l. Meyrin
- Responsibilities
- Central laboratory services (contact listed); sponsorDuties code 4
- Name
- Clario
- Responsibilities
- Central imaging: Dual-energy X-ray absorptiometry (DEXA), body composition, radiological markers
- Name
- Signant Health Inc.
- Responsibilities
- Electronic clinical outcome assessment/vendor services (sponsorDuties code 3)
- Name
- Parexel International Corporation
- Responsibilities
- EUB Services (call center and medical services)
Third parties
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l. Meyrin","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Clario","duties_or_roles":"Central imaging: Dual-energy X-ray absorptiometry (DEXA), body composition, radiological markers","organisation_type":"Health care"}
- {"country":"United States","full_name":"Signant Health Inc.","duties_or_roles":"sponsorDuties: code 3","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Parexel International Corporation","duties_or_roles":"EUB Services (call center and medical services)","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- MK-8591A
- Active Substance
- Doravirine; Islatravir
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- prodAuthStatus: 1; euMpNumber: PRD9952827
- Starting Dose
- Doravirine/Islatravir 100 mg/0.25 mg once-daily
- Dose Levels
- 100 mg doravirine / 0.25 mg islatravir (once-daily)
- Frequency
- Once daily
- Investigational Product Name
- Biktarvy 50 mg/200 mg/25 mg film-coated tablets
- Active Substance
- Bictegravir; Emtricitabine; Tenofovir alafenamide
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- Marketing authorisation EU/1/18/1289/001 and EU/1/18/1289/002 (prodAuthStatus: 2)
- Starting Dose
- Bictegravir 50 mg / Emtricitabine 200 mg / Tenofovir alafenamide 25 mg once-daily
- Dose Levels
- 50 mg / 200 mg / 25 mg (once-daily)
- Frequency
- Once daily
- Investigational Product Name
- Placebo to doravirine/ islatravir
- Modality
- Other
- Investigational Product Name
- Placebo to bictegravir/ emtricitabine/ tenofovir alafenamide
- Modality
- Other
- Combination Treatment
- Yes
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