DOR/ISL in HIV-1 Antiretroviral Treatment-naïve Participants (MK-8591A-053)

Phase 3

Active, not recruiting

• Conditions: HIV-1 Infection
• Interventions: Drug: DOR/ISL; Drug: BIC/FTC/TAF; Drug: Placebo to BIC/FTC/TAF; Drug: Placebo to DOR/ISL

• Registration Number: NCT05705349
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-20
• Study First Submitted QC: 2023-01-20
• Study First Posted: 2023-01-30
• Study Start: 2023-03-08
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-18
• Last Update Posted: 2024-10-21
• Primary Completion: 2025-10-19
• Study Completion: 2029-08-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 500

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DOR/ISL	DOR/ISL	Participants take DOR/ISL and placebo to BIC/FTC/TAF once daily (qd) for 144 weeks.
DOR/ISL	Placebo to BIC/FTC/TAF	Participants take DOR/ISL and placebo to BIC/FTC/TAF once daily (qd) for 144 weeks.
BIC/FTC/TAF	BIC/FTC/TAF	Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 144 weeks.
BIC/FTC/TAF	Placebo to DOR/ISL	Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 144 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL at Week 48	Week 48	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a polymerase chain reaction (PCR) assay with a lower limit of detection of \<50 copies/mL.
Percentage of participants experiencing ≥1 adverse event (AE) through Week 48	Up to 48 weeks	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Percentage of participants discontinuing from study treatment due to an AE through Week 48	Up to 48 weeks	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Secondary Outcome Measures

Name	Time	Method
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96	Week 96	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of \<50 copies/mL.
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144	Week 144	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of \<50 copies/mL.
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48	Week 48	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of \<50 copies/mL.
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96	Week 96	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of \<50 copies/mL.
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144	Week 144	Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of \<50 copies/mL.
Change from baseline in cluster of differentiation 4+ (CD4+) T-cells at Week 48	Baseline (Day 1) and Week 48	CD4+ T-cells are quantified with a T and B lymphocyte and natural killer cell (TBNK) panel.
Change from baseline in CD4+ T-cells at Week 96	Baseline (Day 1) and Week 96	CD4+ T-cells are quantified with a TBNK panel.
Change from baseline in CD4+ T-cells at Week 144	Baseline (Day 1) and Week 144	CD4+ T-cells are quantified with a TBNK panel.
Incidence of viral drug resistance	Up to 96 weeks	Plasma samples will be collected for genotypic and phenotypic HIV-1 viral drug resistance testing and used to assess resistance-associated substitutions and viral susceptibility as applicable during the study.
Change from baseline in body weight at Week 48	Baseline (Day 1) and Week 48	Body weight will be collected throughout the study.
Change from baseline in body weight at Week 96	Baseline (Day 1) and Week 96	Body weight will be collected throughout the study.
Change from baseline in body weight at Week 144	Baseline (Day 1) and Week 144	Body weight will be collected throughout the study.
Percentage of participants experiencing ≥1 AE through Week 144	Up to 144 weeks	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Percentage of participants discontinuing from study treatment due to an AE through Week 144	Up to 144 weeks	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Trial Locations

Locations (131)

Pueblo Family Physicians ( Site 5674); 🇺🇸 Phoenix, Arizona, United States

Pacific Oaks Medical Group ( Site 5681); 🇺🇸 Beverly Hills, California, United States

Ruane Clinical Research Group, Inc ( Site 5658); 🇺🇸 Los Angeles, California, United States

Vivent Health ( Site 5694); 🇺🇸 Denver, Colorado, United States

Washington Health Institute ( Site 5689); 🇺🇸 Washington, District of Columbia, United States

Midway Immunology and Research Center ( Site 5657); 🇺🇸 Fort Pierce, Florida, United States

AHF South Beach ( Site 5663); 🇺🇸 Miami Beach, Florida, United States

AHF The Kinder Medical Group ( Site 5672); 🇺🇸 Miami, Florida, United States

Orlando Immunology Center ( Site 5654); 🇺🇸 Orlando, Florida, United States

CAN Community Health - Sarasota ( Site 5668); 🇺🇸 Sarasota, Florida, United States

Triple O Research Institute, P.A ( Site 5666); 🇺🇸 West Palm Beach, Florida, United States

Emory University and Grady Health System-Medicine ( Site 5690); 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital Midtown Infectious Disease Clinic ( Site 5673); 🇺🇸 Atlanta, Georgia, United States

Atlanta I.D. Group ( Site 5680); 🇺🇸 Atlanta, Georgia, United States

Metro Infectious Diseases Consultants L.L.C. ( Site 5653); 🇺🇸 Decatur, Georgia, United States

Mercer University, Department of Internal Medicine ( Site 5655); 🇺🇸 Macon, Georgia, United States

Rush University Medical Center-Infectious Disease ( Site 5671); 🇺🇸 Chicago, Illinois, United States

University of Illinois at Chicago-Project WISH ( Site 5685); 🇺🇸 Chicago, Illinois, United States

Howard Brown Health Center-Clinical Research ( Site 5665); 🇺🇸 Chicago, Illinois, United States

Be Well Medical Center ( Site 5650); 🇺🇸 Berkley, Michigan, United States

Henry Ford Hospital ( Site 5667); 🇺🇸 Detroit, Michigan, United States

KC CARE Health Center-Clinical Trials ( Site 5670); 🇺🇸 Kansas City, Missouri, United States

Jubilee Clinical Research ( Site 5679); 🇺🇸 Las Vegas, Nevada, United States

Las Vegas Research Center ( Site 5691); 🇺🇸 Las Vegas, Nevada, United States

ID Care ( Site 5676); 🇺🇸 Hillsborough, New Jersey, United States

Saint Michael's Medical Center ( Site 5682); 🇺🇸 Newark, New Jersey, United States

Jacobi Medical Center ( Site 5683); 🇺🇸 Bronx, New York, United States

Columbia University Irving Medical Center-Division of Infectious Diseases ( Site 5688); 🇺🇸 New York, New York, United States

Atrium Health Infectious Disease Kenilworth - Charlotte ( Site 5675); 🇺🇸 Charlotte, North Carolina, United States

Regional Center for Infectious Diseases ( Site 5687); 🇺🇸 Greensboro, North Carolina, United States

University of Cincinnati Medical Center-Infectious Diseases - Outpatient ( Site 5662); 🇺🇸 Cincinnati, Ohio, United States

Central Texas Clinical Research ( Site 5661); 🇺🇸 Austin, Texas, United States

St Hope Foundation ( Site 5659); 🇺🇸 Bellaire, Texas, United States

Prism Health North Texas, Oak Cliff Health Center ( Site 5660); 🇺🇸 Dallas, Texas, United States

North Texas Infectious Diseases Consultants, P.A ( Site 5651); 🇺🇸 Dallas, Texas, United States

AXCES Research - Texas - El Paso ( Site 5692); 🇺🇸 El Paso, Texas, United States

Texas Centers for Infectious Disease Associates ( Site 5656); 🇺🇸 Fort Worth, Texas, United States

DCOL Center for Clinical Research ( Site 5664); 🇺🇸 Longview, Texas, United States

Fundación Huésped ( Site 5850); 🇦🇷 Caba, Buenos Aires, Argentina

Instituto de Investigaciones Clínicas Mar del Plata ( Site 5854); 🇦🇷 Mar del Plata, Buenos Aires, Argentina

Instituto CAICI SRL ( Site 5852); 🇦🇷 Rosario, Santa Fe, Argentina

Fundación IDEAA ( Site 5851); 🇦🇷 Buenos Aires, Argentina

Instituto Oulton ( Site 5853); 🇦🇷 Cordoba, Argentina

Hamilton Health Sciences-Urgent Care Centre ( Site 5750); 🇨🇦 Hamilton, Ontario, Canada

Toronto General Hospital ( Site 5753); 🇨🇦 Toronto, Ontario, Canada

Clinique Medicale lActuel ( Site 5752); 🇨🇦 Montréal, Quebec, Canada

McGill University Health Centre ( Site 5751); 🇨🇦 Montréal, Quebec, Canada

Regina General Hospital ( Site 5754); 🇨🇦 Regina, Saskatchewan, Canada

Hospital hernan henriquez aravena de temuco-Unidad de Investigación Clínica ( Site 5955); 🇨🇱 Temuco, Araucania, Chile

Clinica Universidad Catolica del Maule ( Site 5954); 🇨🇱 Talca, Maule, Chile

Biomedica Research Group-Infectology ( Site 5951); 🇨🇱 Santiago, Region M. De Santiago, Chile

Espacio Eme ( Site 5952); 🇨🇱 Santiago, Region M. De Santiago, Chile

Centro de Investigacion Clinicadela Universidad Catolica ( Site 5953); 🇨🇱 Santiago, Region M. De Santiago, Chile

Universidad de Chile - Hospital Clínico Universidad de Chile-Inmunologia Alergia y VIH ( Site 5950); 🇨🇱 Santiago, Region M. De Santiago, Chile

Ciensalud Ips S A S ( Site 6050); 🇨🇴 Barranquilla, Atlantico, Colombia

Clinica de la Costa S.A.S. ( Site 6055); 🇨🇴 Barranquilla, Atlantico, Colombia

Hospital Universitario San Ignacio-Infectious ( Site 6053); 🇨🇴 Bogota, Distrito Capital De Bogota, Colombia

Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 6051); 🇨🇴 Bogota, Distrito Capital De Bogota, Colombia

Fundación Valle del Lili ( Site 6052); 🇨🇴 Cali, Valle Del Cauca, Colombia

Instituto Dermatológico y Cirugía de Piel "Dr. Huberto Bogaert Díaz" ( Site 8250); 🇩🇴 Santo Domingo De Guzman, Santo Domingo, Dominican Republic

Centre Hospitalier Universitaire de Nice - Hôpital l'Archet ( Site 6153); 🇫🇷 Nice, Alpes-Maritimes, France

Hôpital Avicenne ( Site 6160); 🇫🇷 Bobigny, Ile-de-France, France

Hôpital Saint-Louis ( Site 6159); 🇫🇷 Paris, Ile-de-France, France

Pitie Salpetriere University Hospital ( Site 6156); 🇫🇷 Paris, Ile-de-France, France

Tourcoing Hospital ( Site 6150); 🇫🇷 Tourcoing, Nord, France

Hôpital Bichat - Claude-Bernard ( Site 6162); 🇫🇷 Paris, France

Hôpital Saint Antoine ( Site 6158); 🇫🇷 Paris, France

Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Medizinische Klinik und Poliklinik IV, Sektio; 🇩🇪 München, Bayern, Germany

Universitaetsklinikum Freiburg ( Site 6256); 🇩🇪 Freiburg, Brandenburg, Germany

Universitätsklinikum Bonn-Immunologie ( Site 6250); 🇩🇪 Bonn, Nordrhein-Westfalen, Germany

ICH Study Center GmbH & Co. KG ( Site 6259); 🇩🇪 Hamburg, Germany

Universitaetsklinikum Hamburg-Eppendorf-Infektiologie ( Site 6260); 🇩🇪 Hamburg, Germany

CLINIPHARM ( Site 8352); 🇬🇹 Guatemala, Guatemala

Clínica Médica Especializada en Pediatría e Infectología Pediátrica - Dr. Mario Melgar ( Site 8350); 🇬🇹 Guatemala, Guatemala

CELAN,S.A ( Site 8351); 🇬🇹 Guatemala, Guatemala

Rambam Health Care Campus-Institute of Allergy, Clinical Immunology, ( Site 6751); 🇮🇱 Haifa, Israel

Hadassah Medical Center-Infecious Disease ( Site 6752); 🇮🇱 Jerusalem, Israel

Sheba Medical Center-HIV unit ( Site 6753); 🇮🇱 Ramat Gan, Israel

Sourasky Medical Center ( Site 6754); 🇮🇱 Tel Aviv, Israel

National Hospital Organization Nagoya Medical Center ( Site 6953); 🇯🇵 Nagoya, Aichi, Japan

Tokyo Medical University Hospital ( Site 6954); 🇯🇵 Shinjuku-ku, Tokyo, Japan

Center Hospital of the National Center for Global Health and Medicine ( Site 6951); 🇯🇵 Shinjyuku-ku, Tokyo, Japan

National Hospital Organization Osaka National Hospital ( Site 6952); 🇯🇵 Osaka, Japan

CCR KEMRI (Center for Clinical Research) ( Site 8652); 🇰🇪 Nairobi, Nairobi City, Kenya

PHRD KEMRI (Partners in Health Research & Development) ( Site 8651); 🇰🇪 Nairobi, Nairobi City, Kenya

KEMRI-CMR-RCTP ( Site 8650); 🇰🇪 Kisumu, Kenya

Hospital Sultanah Bahiyah ( Site 7776); 🇲🇾 Alor Setar, Kedah, Malaysia

University Malaya Medical Centre-Clinical Investigation Centre (CIC) ( Site 7777); 🇲🇾 Lembah Pantai, Kuala Lumpur, Malaysia

Hospital Pulau Pinang ( Site 7779); 🇲🇾 George Town, Pulau Pinang, Malaysia

Sarawak General Hospital ( Site 7772); 🇲🇾 Kuching, Sarawak, Malaysia

Hospital Selayang ( Site 7770); 🇲🇾 Batu Caves, Selangor, Malaysia

Hospital Sungai Buloh ( Site 7778); 🇲🇾 Sungai Buloh, Selangor, Malaysia

Hospital Kuala Lumpur ( Site 7773); 🇲🇾 Kuala Lumpur, Malaysia

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 7251); 🇲🇽 Mexico City, Distrito Federal, Mexico

Ponce Medical School Foundation Inc. ( Site 7452); 🇵🇷 Ponce, Puerto Rico

Clinical Research Puerto Rico ( Site 7450); 🇵🇷 San Juan, Puerto Rico

HOPE Clinical Research ( Site 7451); 🇵🇷 San Juan, Puerto Rico

Josha Research ( Site 6652); 🇿🇦 Bloemfontein, Free State, South Africa

Perinatal HIV Research Unit (PHRU)-Adult Treatment and Research ( Site 6654); 🇿🇦 Johannesburg, Gauteng, South Africa

Helen Joseph Hospital-Clinical HIV Research Unit ( Site 6661); 🇿🇦 Johannesburg, Gauteng, South Africa

Ezintsha-Clinical Research Site ( Site 6656); 🇿🇦 Johannesburg, Gauteng, South Africa

Wentworth Hospital ( Site 6653); 🇿🇦 Durban, Kwazulu-Natal, South Africa

Qhakaza Mbokodo Research Clinic ( Site 6659); 🇿🇦 Ladysmith, Kwazulu-Natal, South Africa

Human Sciences Research Council-Centre for Community Based Research ( Site 6664); 🇿🇦 Pietermaritzburg, Kwazulu-Natal, South Africa

Madibeng Centre for Research ( Site 6660); 🇿🇦 Brits, North-West, South Africa

Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 6657); 🇿🇦 Cape Town, Western Cape, South Africa

Desmond Tutu Health Foundation ( Site 6651); 🇿🇦 Cape Town, Western Cape, South Africa

Be Part Yoluntu Centre ( Site 6650); 🇿🇦 Paarl, Western Cape, South Africa

Hospital General Universitario de Elche-Infectius Disease ( Site 6358); 🇪🇸 Elche, Alicante, Spain

Hospital Germans Trias i Pujol-Fundació Lluita contra la Sida ( Site 6351); 🇪🇸 Badalona, Barcelona, Spain

HOSPITAL CLÍNIC DE BARCELONA-Infection Day Hospital ( Site 6350); 🇪🇸 Barcelona, Cataluna, Spain

Hospital Universitari de Bellvitge ( Site 6360); 🇪🇸 L'Hospitalet De Llobregat,Barcelona, Cataluna, Spain

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-Unidad de Enfermedades Infecciosas ( Site 6353); 🇪🇸 Madrid, Madrid, Comunidad De, Spain

Hospital Universitario Ramón y Cajal-ENFERMEDADES INFECCIOSAS ( Site 6361); 🇪🇸 Madrid, Madrid, Comunidad De, Spain

Hospital Universitari Vall d'Hebron-Infectious Diseases: HIV unit ( Site 6352); 🇪🇸 Barcelona, Spain

Hospital Universitario Fundación Jiménez Díaz-Internal Medicine. Infectious disease ( Site 6357); 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre ( Site 6355); 🇪🇸 Madrid, Spain

Hospital Universitario La Paz ( Site 6354); 🇪🇸 Madrid, Spain

Hospital Universitario Virgen de la Victoria ( Site 6359); 🇪🇸 Malaga, Spain

University Hospital Basel-Infectiology ( Site 8151); 🇨🇭 Basel, Basel-Stadt, Switzerland

Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 8150); 🇨🇭 Genève, Geneve, Switzerland

HIV Netherlands Australia Thailand Research Collaboration ( Site 7851); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

Faculty of Medicine Siriraj Hospital-Preventive and social ( Site 7850); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

Research Institute for Health Sciences-Research Institute for Health Sciences Building 1 ( Site 7852; 🇹🇭 Chiang Mai, Thailand

Hacettepe Universite Hastaneleri ( Site 7650); 🇹🇷 Altindağ, Ankara, Turkey

Ankara Bilkent Şehir Hastanesi-Infectious Disease and Clinical Microbiology ( Site 7659); 🇹🇷 Ankara, Turkey

Southmead Hospital ( Site 7952); 🇬🇧 Bristol, Bristol, City Of, United Kingdom

Royal London Hospital ( Site 7951); 🇬🇧 London, England, United Kingdom

The Hathersage Centre ( Site 7953); 🇬🇧 Manchester, England, United Kingdom

King's College Hospital ( Site 7950); 🇬🇧 London, London, City Of, United Kingdom

The Mortimer Market Centre for Sexual Health and HIV Research ( Site 7954); 🇬🇧 London, London, City Of, United Kingdom