Study of Doravirine/Islatravir (DOR/ISL 100 mg/0.75 mg) to Evaluate the Antiretroviral Activity, Safety, and Tolerability in Treatment-Naïve Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-020)
- Conditions
- HIV-1 Infection
- Interventions
- Registration Number
- NCT04233879
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This is a phase 3, randomized, controlled, double-blind, multisite clinical study of a once-daily fixed dose combination (FDC) of 100 mg doravirine/0.75 mg islatravir (DOR/ISL \[also known as MK-8591A\]) in treatment-naïve participants with human immunodeficiency virus type-1 (HIV-1) infection. The primary objectives are to evaluate the antiretroviral activity, safety, and tolerability of DOR/ISL compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that DOR/ISL is noninferior or superior to BIC/FTC/TAF treatment based on the percentage of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL at Week 48.
- Detailed Description
Double-blind treatment with the assigned intervention occurs from Day 1 to Week 96, followed by an open-label portion up to Week 144. Participants who benefit from treatment in the opinion of the Investigator may continue their assigned intervention up to Week 168 (or until they have the option to enroll in a DOR/ISL 100 mg/0.25 mg study, whichever is sooner).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 599
- Is human immunodeficiency virus type 1 (HIV-1) positive
- Is naïve to antiretroviral therapy (ART) defined as having received ≤10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection including prevention of mother-to-child transmission up to 1 month prior to screening.
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); 2) Is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis); 3) A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention; 4) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required
- Has HIV-2 infection
- Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
- Has an active diagnosis of hepatitis due to any cause, including active HBV infection (defined as hepatitis B surface antigen [HBsAg]-positive or hepatitis B virus deoxyribonucleic acid [HBV DNA]-positive)
- Has a history of malignancy ≤5 years prior to signing 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
- Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
- Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapy from 45 days prior to Day 1 through the study intervention period
- Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study intervention period
- Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, or any study intervention
- Has exclusionary laboratory values within 45 days prior to Day 1
- Is female and is expecting to conceive or donate eggs at any time during the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1: DOR/ISL DOR/ISL Treatment-naïve participants with HIV-1 receive blinded DOR/ISL and placebo to BIC/FTC/TAF once daily (QD) from Day 1 to Week 96, and open-label DOR/ISL up to Week 144. Participants who are benefitting from treatment are then eligible to continue on open-label DOR/ISL up to Week 168. Group 1: DOR/ISL Placebo to BIC/FTC/TAF Treatment-naïve participants with HIV-1 receive blinded DOR/ISL and placebo to BIC/FTC/TAF once daily (QD) from Day 1 to Week 96, and open-label DOR/ISL up to Week 144. Participants who are benefitting from treatment are then eligible to continue on open-label DOR/ISL up to Week 168. Group 2: BIC/FTC/TAF Placebo to DOR/ISL Treatment-naïve participants with HIV-1 receive blinded BIC/FTC/TAF and placebo to DOR/ISL QD from Day 1 to Week 96, and open-label BIC/FTC/TAF up to Week 144. Participants who are benefitting from treatment are then eligible to continue on open-label BIC/FTC/TAF up to Week 168. Group 2: BIC/FTC/TAF BIC/FTC/TAF Treatment-naïve participants with HIV-1 receive blinded BIC/FTC/TAF and placebo to DOR/ISL QD from Day 1 to Week 96, and open-label BIC/FTC/TAF up to Week 144. Participants who are benefitting from treatment are then eligible to continue on open-label BIC/FTC/TAF up to Week 168.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 Week 48 HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott Real Time polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48 was presented using the FDA Snapshot missing data approach.
Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48 Up to approximately 48 weeks An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experience an AE was reported.
Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48 Up to approximately 48 weeks An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE were reported.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144 Week 144 The percentage of participants with HIV-1 RNA \<50 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 144 will be presented using the FDA Snapshot missing data approach.
Change From Baseline in Body Weight at Week 144 Baseline (Day 1) and Week 144 Body weight was measured at baseline and at Week 144. Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight at Week 144 will be presented.
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 Week 96 The percentage of participants with HIV-1 RNA \<50 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 96 will be presented using the FDA Snapshot missing data approach.
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48 Week 48 The percentage of participants with HIV-1 RNA \<40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<40 copies/mL at Week 48 will be presented using the FDA Snapshot missing data approach.
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48 Week 48 The percentage of participants with HIV-1 RNA \<200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 48 will be presented using the FDA Snapshot missing data approach.
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96 Week 96 The percentage of participants with HIV-1 RNA \<40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<40 copies/mL at Week 96 will be presented using the FDA Snapshot missing data approach.
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96 Week 96 The percentage of participants with HIV-1 RNA \<200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 96 will be presented using the FDA Snapshot missing data approach.
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144 Week 144 The percentage of participants with HIV-1 RNA \<40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<40 copies/mL at Week 144 will be presented using the FDA Snapshot missing data approach.
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144 Week 144 The percentage of participants with HIV-1 RNA \<200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 144 will be presented using the FDA Snapshot missing data approach.
Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48 Baseline (Day 1) and Week 48 Plasma CD4+ T-cell count was measured in cells/mm\^3 for baseline and 48 weeks by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 48 was presented.
Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 96 Baseline (Day 1) and Week 96 Plasma CD4+ T-cell count will be measured in cells/mm\^3 for baseline and 96 weeks by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 96 will be presented.
Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 144 Baseline (Day 1) and Week 144 Plasma CD4+ T-cell count will be measured in cells/mm\^3 for baseline and 144 weeks by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 144 will be presented.
Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48 Week 48 RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 48 was presented.
Incidence of Viral RASs at Week 96 Week 96 RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrate viral RASs at Week 96 will be presented.
Incidence of Viral RASs at Week 144 Week 144 RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrate viral RASs at Week 144 will be presented.
Change From Baseline in Body Weight at Week 48 Baseline (Day 1) and Week 48 Body weight was measured at baseline and at Week 48. Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight at Week 48 was presented.
Change From Baseline in Body Weight at Week 96 Baseline (Day 1) and Week 96 Body weight was measured at baseline and at Week 96. Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight at Week 96 will be presented.
Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 156 Up to approximately 156 weeks An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experience an AE will be reported.
Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 156 Up to approximately 156 weeks An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE will be reported.
Trial Locations
- Locations (95)
Ruane Clinical Research Group, Inc. ( Site 5624)
🇺🇸Los Angeles, California, United States
The Kinder Medical Group ( Site 5615)
🇺🇸Miami, Florida, United States
University of Pennsylvania ( Site 5630)
🇺🇸Philadelphia, Pennsylvania, United States
Floridian Clinical Research, LLC ( Site 5625)
🇺🇸Miami Lakes, Florida, United States
North Texas ID Consultants, PA ( Site 5604)
🇺🇸Dallas, Texas, United States
Toronto General Hospital - University Health Network ( Site 5705)
🇨🇦Toronto, Ontario, Canada
A.O.R.N. dei Colli - Ospedale Cotugno ( Site 6407)
🇮🇹Napoli, Campania, Italy
Wits Health Consortium. Clinical HIV Research Unit ( Site 6614)
🇿🇦Johannesburg, Gauteng, South Africa
Ezintsha ( Site 6609)
🇿🇦Johannesburg, Gauteng, South Africa
Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 6617)
🇿🇦Cape Town, Western Cape, South Africa
Hennepin Healthcare-Hennepin Healthcare-ID ( Site 5633)
🇺🇸Minneapolis, Minnesota, United States
Clinica Universidad Catolica del Maule ( Site 5909)
🇨🇱Talca, Maule, Chile
Hopital Avicenne ( Site 6102)
🇫🇷Bobigny, Seine-Saint-Denis, France
Pueblo Family Physicians ( Site 5606)
🇺🇸Phoenix, Arizona, United States
Instituto CAICI ( Site 5803)
🇦🇷Rosario, Santa Fe, Argentina
Helios Salud S.A. ( Site 5802)
🇦🇷Ciudad Autonoma de Buenos Aires, Caba, Argentina
Instituto Oulton ( Site 5804)
🇦🇷Cordoba, Argentina
Texas Centers for Infectious Disease Associates P.A. ( Site 5619)
🇺🇸Fort Worth, Texas, United States
Azienda USL di Pescara-Presidio Ospedaliero di Pescara ( Site 6413)
🇮🇹Pescara, Italy
Istituto Nazionale per Le Malattie Infettive Lazzaro Spallanzani ( Site 6405)
🇮🇹Roma, Italy
Wentworth Hospital ( Site 6607)
🇿🇦Durban, Kwazulu-Natal, South Africa
National Taiwan University Hospital ( Site 7100)
🇨🇳Taipei, Taiwan
Hospital Universitario Fundacion Jimenez Diaz ( Site 6307)
🇪🇸Madrid, Spain
National Hospital Organization Nagoya Medical Center ( Site 6903)
🇯🇵Nagoya, Aichi, Japan
Hospital General de Elche ( Site 6308)
🇪🇸Elche, Alicante, Spain
Hospital Universitari Germans Trias i Pujol ( Site 6301)
🇪🇸Badalona, Barcelona, Spain
Hospital Universitari de Bellvitge ( Site 6312)
🇪🇸LHospitalet de Llobregat, Barcelona, Spain
Be Part Yoluntu Centre ( Site 6603)
🇿🇦Mbekweni, Paarl, Western Cape, South Africa
Hospital Universitario 12 de Octubre ( Site 6305)
🇪🇸Madrid, Spain
National Cheng Kung University Hospital ( Site 7101)
🇨🇳Tainan, Taiwan
Kumamoto University Hospital ( Site 6905)
🇯🇵Kumamoto, Japan
National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 69
🇯🇵Osaka, Japan
University of Alabama at Birmingham 1917 Research Clinic ( Site 5610)
🇺🇸Birmingham, Alabama, United States
Midway Immunology and Research ( Site 5622)
🇺🇸Fort Pierce, Florida, United States
Orlando Immunology Center ( Site 5613)
🇺🇸Orlando, Florida, United States
Triple O Research Institute, P.A. ( Site 5621)
🇺🇸West Palm Beach, Florida, United States
CAN Community Health ( Site 5627)
🇺🇸Sarasota, Florida, United States
Columbus Regional Research Institute ( Site 5616)
🇺🇸Columbus, Georgia, United States
Infectious Disease Specialists Of Atlanta PC ( Site 5608)
🇺🇸Decatur, Georgia, United States
Kansas City CARE Clinic ( Site 5607)
🇺🇸Kansas City, Missouri, United States
Saint Hope Foundation, Inc. ( Site 5629)
🇺🇸Bellaire, Texas, United States
IDEAA Foundation ( Site 5807)
🇦🇷Buenos Aires, Caba, Argentina
Fundación Huesped ( Site 5801)
🇦🇷C.a.b.a, Caba, Argentina
Clinique Medicale L Actuel ( Site 5714)
🇨🇦Montreal, Quebec, Canada
Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 5703)
🇨🇦Hamilton, Ontario, Canada
Clinica Arauco Salud ( Site 5900)
🇨🇱Santiago, Region M. De Santiago, Chile
Hospital Universitario San Ignacio ( Site 6005)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
Hospital Dr. Hernan Henriquez Aravena ( Site 5905)
🇨🇱Temuco, Araucania, Chile
Fundacion Arriaran ( Site 5901)
🇨🇱Santiago, Region M. De Santiago, Chile
Hospital Clinico de la Universidad Catolica ( Site 5903)
🇨🇱Santiago, Region M. De Santiago, Chile
McGill University Health Center - Research Institute-CVIS Clinical Research Unit ( Site 5702)
🇨🇦Montreal, Quebec, Canada
Fundacion Valle del Lili ( Site 6001)
🇨🇴Cali, Valle Del Cauca, Colombia
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 6006)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
CHU de Bordeaux. Hopital Pellegrin ( Site 6116)
🇫🇷Bordeaux, Gironde, France
Centre Hospitalier Regional du Orleans ( Site 6108)
🇫🇷Orleans, Centre, France
Hopital Francois Mitterrand ( Site 6119)
🇫🇷Dijon, Cote-d Or, France
A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 6124)
🇫🇷Paris, Ain, France
Hopital de la Croix-Rousse ( Site 6127)
🇫🇷Lyon, Rhone-Alpes, France
A.P.H. Paris, Hopital Saint Louis ( Site 6114)
🇫🇷Paris, France
Hopital Pitie Salpetriere ( Site 6111)
🇫🇷Paris, France
Hopital Saint-Antoine ( Site 6113)
🇫🇷Paris, France
Universitaetsklinik Freiburg ( Site 6206)
🇩🇪Freiburg, Baden-Wurttemberg, Germany
Klinikum der LMU München ( Site 6204)
🇩🇪Muenchen, Bayern, Germany
Infektiologikum ( Site 6201)
🇩🇪Frankfurt am Main, Hessen, Germany
Universitaetsklinikum Bonn ( Site 6200)
🇩🇪Bonn, Nordrhein-Westfalen, Germany
EPIMED- Ges. f. epidemiolog. u. klin. Forschung in der Medizin mbH ( Site 6208)
🇩🇪Berlin, Germany
Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 6210)
🇩🇪Hamburg, Germany
Rambam Medical Center ( Site 6701)
🇮🇱Haifa, Israel
Hadassah Ein Kerem Medical Center ( Site 6702)
🇮🇱Jerusalem, Israel
Kaplan Medical Center ( Site 6700)
🇮🇱Rehovot, Israel
Sourasky Medical Center ( Site 6705)
🇮🇱Tel Aviv, Israel
Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 6404)
🇮🇹Modena, Emilia-Romagna, Italy
ASST Papa Giovanni XXIII ( Site 6411)
🇮🇹Bergamo, Lombardia, Italy
Ospedale Amedeo di Savoia ( Site 6414)
🇮🇹Torino, Piemonte, Italy
Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 6401)
🇮🇹Milano, Italy
Salute San Raffaele ( Site 6402)
🇮🇹Milano, Italy
Azienda Ospedaliera San Paolo ( Site 6403)
🇮🇹Milano, Italy
Ospedale San Gerardo ASST Monza ( Site 6412)
🇮🇹Monza, Monza E Brianza, Italy
ASST Fatebenefratelli-Ospedale Sacco ( Site 6400)
🇮🇹Milano, Italy
IRCCS Policlinico San Matteo ( Site 6410)
🇮🇹Pavia, Italy
Tokyo Medical University Hospital ( Site 6904)
🇯🇵Tokyo, Japan
Center Hospital of the National Center for Global Health and Medicine ( Site 6901)
🇯🇵Tokyo, Japan
Chris Hani Baragwanath Hospital - ICU ( Site 6608)
🇿🇦Johannesburg, Gauteng, South Africa
JOSHA Research ( Site 6605)
🇿🇦Bloemfontein, Free State, South Africa
Hospital Vall D Hebron ( Site 6302)
🇪🇸Barcelona, Cataluna, Spain
Hospital General Universitario Gregorio Maranon ( Site 6303)
🇪🇸Madrid, Spain
Hospital Clinic i Provincial ( Site 6300)
🇪🇸Barcelona, Cataluna, Spain
Hospital Universitario La Paz ( Site 6304)
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria ( Site 6309)
🇪🇸Malaga, Spain
Kaohsiung Veterans General Hospital ( Site 7102)
🇨🇳Kaohsiung, Taiwan
MVZ Munchen am Goetheplatz ( Site 6202)
🇩🇪Muenchen, Bayern, Germany
Chaim Sheba Medical Center. ( Site 6704)
🇮🇱Ramat-Gan, Israel
Centro Cardiovascular Cardiosur ( Site 5907)
🇨🇱Santiago, Region M. De Santiago, Chile
Centre Hospitalier de Tourcoing ( Site 6100)
🇫🇷Tourcoing, Nord, France
Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 6613)
🇿🇦Cape Town, Western Cape, South Africa