Clinical trial NCT05705349: DOR/ISL in HIV-1 Antiretroviral Treatment-naïve Participants (MK-8591A-053)
Official title: A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in HIV-1 Infected Treatment-Naïve Participants
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: HIV-1 Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2023-01-30
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, active-controlled, double-blind clinical study designed to evaluate the antiretroviral activity, safety, and tolerability of doravirine/islatravir (DOR/ISL \[MK-8591A\]) in treatment-naïve participants with human immunodeficiency virus type 1 (HIV-1) infection. It is hypothesized that DOR/ISL is non-inferior to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL at Week 48.


Eligibility criteria: Inclusion Criteria:

* Is HIV-1 positive with plasma HIV-1 RNA ≥500 copies/mL at screening
* Is naïve to antiretroviral therapy (ART) defined as having received no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection
* If 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:

* Has HIV-2 infection
* Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
* Has a diagnosis of an active AIDS-defining opportunistic infection within 30 days prior to screening
* Has active hepatitis B infection (defined as hepatitis B surface antigen \[HBsAg\]-positive or HBV deoxyribonucleic acid \[DNA\]-positive).
* Has chronic hepatitis C virus (HCV) infection (detectable HCV ribonucleic acid \[RNA\]) and lab values are consistent with cirrhosis
* 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
* 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

Primary outcomes:
measure: Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of participants experiencing ≥1 adverse event (AE) through Week 48
timeFrame: Up to 48 weeks
measure: Percentage of participants discontinuing from study treatment due to an AE through Week 48
timeFrame: Up to 48 weeks
Secondary outcomes:
measure: Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96
timeFrame: Week 96
measure: Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144
timeFrame: Week 144
measure: Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96
timeFrame: Week 96
measure: Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144
timeFrame: Week 144
measure: Change from baseline in cluster of differentiation 4+ (CD4+) T-cells at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change from baseline in CD4+ T-cells at Week 96
timeFrame: Baseline (Day 1) and Week 96
measure: Change from baseline in CD4+ T-cells at Week 144
timeFrame: Baseline (Day 1) and Week 144
measure: Incidence of viral drug resistance
timeFrame: Up to 96 weeks
measure: Change from baseline in body weight at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change from baseline in body weight at Week 96
timeFrame: Baseline (Day 1) and Week 96
measure: Change from baseline in body weight at Week 144
timeFrame: Baseline (Day 1) and Week 144
measure: Percentage of participants experiencing ≥1 AE through Week 144
timeFrame: Up to 144 weeks
measure: Percentage of participants discontinuing from study treatment due to an AE through Week 144
timeFrame: Up to 144 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pueblo Family Physicians ( Site 5674)
state: Arizona
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group ( Site 5681)
state: California
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group, Inc ( Site 5658)
state: California
city: Denver
country: United States
facility: Vivent Health ( Site 5694)
state: Colorado
city: Washington
country: United States
facility: Washington Health Institute ( Site 5689)
state: District of Columbia
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center ( Site 5657)
state: Florida
city: Miami Beach
country: United States
facility: AHF South Beach ( Site 5663)
state: Florida
city: Miami
country: United States
facility: AHF The Kinder Medical Group ( Site 5672)
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center ( Site 5654)
state: Florida
city: Sarasota
country: United States
facility: CAN Community Health - Sarasota ( Site 5668)
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A ( Site 5666)
state: Florida
city: Atlanta
country: United States
facility: Emory University and Grady Health System-Medicine ( Site 5690)
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown Infectious Disease Clinic ( Site 5673)
state: Georgia
city: Atlanta
country: United States
facility: Atlanta I.D. Group ( Site 5680)
state: Georgia
city: Decatur
country: United States
facility: Metro Infectious Diseases Consultants L.L.C. ( Site 5653)
state: Georgia
city: Macon
country: United States
facility: Mercer University, Department of Internal Medicine ( Site 5655)
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center-Infectious Disease ( Site 5671)
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago-Project WISH ( Site 5685)
state: Illinois
city: Chicago
country: United States
facility: Howard Brown Health Center-Clinical Research ( Site 5665)
state: Illinois
city: Berkley
country: United States
facility: Be Well Medical Center ( Site 5650)
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital ( Site 5667)
state: Michigan
city: Kansas City
country: United States
facility: KC CARE Health Center-Clinical Trials ( Site 5670)
state: Missouri
city: Las Vegas
country: United States
facility: Jubilee Clinical Research ( Site 5679)
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Research Center ( Site 5691)
state: Nevada
city: Hillsborough
country: United States
facility: ID Care ( Site 5676)
state: New Jersey
city: Newark
country: United States
facility: Saint Michael's Medical Center ( Site 5682)
state: New Jersey
city: Bronx
country: United States
facility: Jacobi Medical Center ( Site 5683)
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center-Division of Infectious Diseases ( Site 5688)
state: New York
city: Charlotte
country: United States
facility: Atrium Health Infectious Disease Kenilworth - Charlotte ( Site 5675)
state: North Carolina
city: Greensboro
country: United States
facility: Regional Center for Infectious Diseases ( Site 5687)
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center-Infectious Diseases - Outpatient ( Site 5662)
state: Ohio
city: Austin
country: United States
facility: Central Texas Clinical Research ( Site 5661)
state: Texas
city: Bellaire
country: United States
facility: St Hope Foundation ( Site 5659)
state: Texas
city: Dallas
country: United States
facility: Prism Health North Texas, Oak Cliff Health Center ( Site 5660)
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, P.A ( Site 5651)
state: Texas
city: El Paso
country: United States
facility: AXCES Research - Texas - El Paso ( Site 5692)
state: Texas
city: Fort Worth
country: United States
facility: Texas Centers for Infectious Disease Associates ( Site 5656)
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research ( Site 5664)
state: Texas
city: Caba
country: Argentina
facility: Fundación Huésped ( Site 5850)
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clínicas Mar del Plata ( Site 5854)
state: Buenos Aires
city: Rosario
country: Argentina
facility: Instituto CAICI SRL ( Site 5852)
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Fundación IDEAA ( Site 5851)
city: Cordoba
country: Argentina
facility: Instituto Oulton ( Site 5853)
city: Hamilton
country: Canada
facility: Hamilton Health Sciences-Urgent Care Centre ( Site 5750)
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital ( Site 5753)
state: Ontario
city: Montréal
country: Canada
facility: Clinique Medicale lActuel ( Site 5752)
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre ( Site 5751)
state: Quebec
city: Regina
country: Canada
facility: Regina General Hospital ( Site 5754)
state: Saskatchewan
city: Temuco
country: Chile
facility: Hospital hernan henriquez aravena de temuco-Unidad de Investigación Clínica ( Site 5955)
state: Araucania
city: Talca
country: Chile
facility: Clinica Universidad Catolica del Maule ( Site 5954)
state: Maule
city: Santiago
country: Chile
facility: Biomedica Research Group-Infectology ( Site 5951)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Espacio Eme ( Site 5952)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Centro de Investigacion Clinicadela Universidad Catolica ( Site 5953)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Universidad de Chile - Hospital Clínico Universidad de Chile-Inmunologia Alergia y VIH ( Site 5950)
state: Region M. De Santiago
city: Barranquilla
country: Colombia
facility: Ciensalud Ips S A S ( Site 6050)
state: Atlantico
city: Barranquilla
country: Colombia
facility: Clinica de la Costa S.A.S. ( Site 6055)
state: Atlantico
city: Bogota
country: Colombia
facility: Hospital Universitario San Ignacio-Infectious ( Site 6053)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 6051)
state: Distrito Capital De Bogota
city: Cali
country: Colombia
facility: Fundación Valle del Lili ( Site 6052)
state: Valle Del Cauca
city: Santo Domingo De Guzman
country: Dominican Republic
facility: Instituto Dermatológico y Cirugía de Piel "Dr. Huberto Bogaert Díaz" ( Site 8250)
state: Santo Domingo
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice - Hôpital l'Archet ( Site 6153)
state: Alpes-Maritimes
city: Bobigny
country: France
facility: Hôpital Avicenne ( Site 6160)
state: Ile-de-France
city: Paris
country: France
facility: Hôpital Saint-Louis ( Site 6159)
state: Ile-de-France
city: Paris
country: France
facility: Pitie Salpetriere University Hospital ( Site 6156)
state: Ile-de-France
city: Tourcoing
country: France
facility: Tourcoing Hospital ( Site 6150)
state: Nord
city: Paris
country: France
facility: Hôpital Bichat - Claude-Bernard ( Site 6162)
city: Paris
country: France
facility: Hôpital Saint Antoine ( Site 6158)
city: München
country: Germany
facility: Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Medizinische Klinik und Poliklinik IV, Sektio
state: Bayern
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg ( Site 6256)
state: Brandenburg
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn-Immunologie ( Site 6250)
state: Nordrhein-Westfalen
city: Hamburg
country: Germany
facility: ICH Study Center GmbH & Co. KG ( Site 6259)
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf-Infektiologie ( Site 6260)
city: Guatemala
country: Guatemala
facility: CLINIPHARM ( Site 8352)
city: Guatemala
country: Guatemala
facility: Clínica Médica Especializada en Pediatría e Infectología Pediátrica - Dr. Mario Melgar ( Site 8350)
city: Guatemala
country: Guatemala
facility: CELAN,S.A ( Site 8351)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Institute of Allergy, Clinical Immunology, ( Site 6751)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Infecious Disease ( Site 6752)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-HIV unit ( Site 6753)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 6754)
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center ( Site 6953)
state: Aichi
city: Shinjuku-ku
country: Japan
facility: Tokyo Medical University Hospital ( Site 6954)
state: Tokyo
city: Shinjyuku-ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine ( Site 6951)
state: Tokyo
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital ( Site 6952)
city: Nairobi
country: Kenya
facility: CCR KEMRI (Center for Clinical Research) ( Site 8652)
state: Nairobi City
city: Nairobi
country: Kenya
facility: PHRD KEMRI (Partners in Health Research & Development) ( Site 8651)
state: Nairobi City
city: Kisumu
country: Kenya
facility: KEMRI-CMR-RCTP ( Site 8650)
city: Alor Setar
country: Malaysia
facility: Hospital Sultanah Bahiyah ( Site 7776)
state: Kedah
city: Lembah Pantai
country: Malaysia
facility: University Malaya Medical Centre-Clinical Investigation Centre (CIC) ( Site 7777)
state: Kuala Lumpur
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang ( Site 7779)
state: Pulau Pinang
city: Kuching
country: Malaysia
facility: Sarawak General Hospital ( Site 7772)
state: Sarawak
city: Batu Caves
country: Malaysia
facility: Hospital Selayang ( Site 7770)
state: Selangor
city: Sungai Buloh
country: Malaysia
facility: Hospital Sungai Buloh ( Site 7778)
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur ( Site 7773)
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 7251)
state: Distrito Federal
city: Ponce
country: Puerto Rico
facility: Ponce Medical School Foundation Inc. ( Site 7452)
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico ( Site 7450)
city: San Juan
country: Puerto Rico
facility: HOPE Clinical Research ( Site 7451)
city: Bloemfontein
country: South Africa
facility: Josha Research ( Site 6652)
state: Free State
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit (PHRU)-Adult Treatment and Research ( Site 6654)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Helen Joseph Hospital-Clinical HIV Research Unit ( Site 6661)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Ezintsha-Clinical Research Site ( Site 6656)
state: Gauteng
city: Durban
country: South Africa
facility: Wentworth Hospital ( Site 6653)
state: Kwazulu-Natal
city: Ladysmith
country: South Africa
facility: Qhakaza Mbokodo Research Clinic ( Site 6659)
state: Kwazulu-Natal
city: Pietermaritzburg
country: South Africa
facility: Human Sciences Research Council-Centre for Community Based Research ( Site 6664)
state: Kwazulu-Natal
city: Brits
country: South Africa
facility: Madibeng Centre for Research ( Site 6660)
state: North-West
city: Cape Town
country: South Africa
facility: Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 6657)
state: Western Cape
city: Cape Town
country: South Africa
facility: Desmond Tutu Health Foundation ( Site 6651)
state: Western Cape
city: Paarl
country: South Africa
facility: Be Part Yoluntu Centre ( Site 6650)
state: Western Cape
city: Elche
country: Spain
facility: Hospital General Universitario de Elche-Infectius Disease ( Site 6358)
state: Alicante
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol-Fundació Lluita contra la Sida ( Site 6351)
state: Barcelona
city: Barcelona
country: Spain
facility: HOSPITAL CLÍNIC DE BARCELONA-Infection Day Hospital ( Site 6350)
state: Cataluna
city: L'Hospitalet De Llobregat,Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge ( Site 6360)
state: Cataluna
city: Madrid
country: Spain
facility: HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-Unidad de Enfermedades Infecciosas ( Site 6353)
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal-ENFERMEDADES INFECCIOSAS ( Site 6361)
state: Madrid, Comunidad De
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Infectious Diseases: HIV unit ( Site 6352)
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz-Internal Medicine. Infectious disease ( Site 6357)
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre ( Site 6355)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 6354)
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria ( Site 6359)
city: Basel
country: Switzerland
facility: University Hospital Basel-Infectiology ( Site 8151)
state: Basel-Stadt
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 8150)
state: Geneve
city: Bangkok
country: Thailand
facility: HIV Netherlands Australia Thailand Research Collaboration ( Site 7851)
state: Krung Thep Maha Nakhon
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital-Preventive and social ( Site 7850)
state: Krung Thep Maha Nakhon
city: Chiang Mai
country: Thailand
facility: Research Institute for Health Sciences-Research Institute for Health Sciences Building 1 ( Site 7852
city: Altindağ
country: Turkey
facility: Hacettepe Universite Hastaneleri ( Site 7650)
state: Ankara
city: Ankara
country: Turkey
facility: Ankara Bilkent Şehir Hastanesi-Infectious Disease and Clinical Microbiology ( Site 7659)
city: Bristol
country: United Kingdom
facility: Southmead Hospital ( Site 7952)
state: Bristol, City Of
city: London
country: United Kingdom
facility: Royal London Hospital ( Site 7951)
state: England
city: Manchester
country: United Kingdom
facility: The Hathersage Centre ( Site 7953)
state: England
city: London
country: United Kingdom
facility: King's College Hospital ( Site 7950)
state: London, City Of
city: London
country: United Kingdom
facility: The Mortimer Market Centre for Sexual Health and HIV Research ( Site 7954)
state: London, City Of
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: