Randomized, Double-blind, Efficacy, and Safety Study of Doravirine/Islatravir (DOR/ISL) in Treatment-naïve Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-020)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group 1: DOR/ISL Treatment-naïve participants with HIV-1 receive DOR/ISL and placebo to BIC/FTC/TAF once daily (QD) for 96 weeks. |
Drug: DOR/ISL
100 mg DOR/0.75 mg ISL FDC tablet taken once daily by mouth.
Other Names:
Drug: Placebo to BIC/FTC/TAF
Placebo tablet matched to BIC/FTC/TAF taken by mouth.
|
| Active Comparator: Group 2: BIC/FTC/TAF Treatment-naïve participants with HIV-1 receive BIC/FTC/TAF and placebo to DOR/ISL QD for 96 weeks. |
Drug: BIC/FTC/TAF
BIC/FTC/TAF 50/200/25 mg FDC tablet taken once daily by mouth.
Other Names:
Drug: Placebo to DOR/ISL
Placebo tablet matched to DOR/ISL taken by mouth.
|
Outcome Measures
Primary Outcome Measures
- Percentage of participants with HIV-1 RNA <50 copies/mL [Week 48]
The percentage of participants with HIV-1 RNA <50 copies/mL will be determined at the central laboratory with an Abbott Real Time Polymerase Chain Reaction (PCR) assay with a lower limit of detection (LLOD) of 40 copies/mL.
- Percentage of participants experiencing ≥1 adverse events (AEs) [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 interventions.
- Percentage of participants discontinuing from study treatment due to AE(s) [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 interventions.
Secondary Outcome Measures
- Percentage of participants with HIV-1 RNA <50 copies/mL [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.
- Percentage of participants with HIV-1 RNA <50 copies/mL [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.
- Percentage of participants with HIV-1 RNA <40 copies/mL [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.
- Percentage of participants with HIV-1 RNA <200 copies/mL [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.
- Percentage of participants with HIV-1 RNA <40 copies/mL [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.
- Percentage of participants with HIV-1 RNA <200 copies/mL [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.
- Percentage of participants with HIV-1 RNA <40 copies/mL [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.
- Percentage of participants with HIV-1 RNA <200 copies/mL [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.
- Change from baseline in cluster of differentiation 4+ (CD4+) T-cell counts [Day 1 (baseline) and Week 48]
CD4+ T-cell counts will be measured by a central laboratory.
- Change from baseline in cluster of differentiation 4+ (CD4+) T-cell counts [Day 1 (baseline) and Week 96]
CD4+ T-cell counts will be measured by a central laboratory.
- Change from baseline in cluster of differentiation 4+ (CD4+) T-cell counts [Day 1 (baseline) and Week 144]
CD4+ T-cell counts will be measured by a central laboratory.
- Incidence of viral resistance-associated substitutions (RASs) [Week 48]
The incidence of viral RASs will be determined.
- Incidence of viral RASs [Week 96]
The incidence of viral RASs will be determined.
- Incidence of viral RASs [Week 144]
The incidence of viral RASs will be determined.
- Change from baseline in body weight [Day 1 (baseline) and Week 48]
The change from baseline in participant body weight will be determined.
- Change from baseline in body weight [Day 1 (baseline) and Week 96]
The change from baseline in participant body weight will be determined.
- Change from baseline in body weight [Day 1 (baseline) and Week 144]
The change from baseline in participant body weight will be determined.
- Percentage of participants experiencing ≥1 adverse events (AEs) [Up to 156 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 interventions.
- Percentage of participants discontinuing from study treatment due to AE(s) [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 interventions.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Is 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
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 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham 1917 Research Clinic ( Site 5610) | Birmingham | Alabama | United States | 35222 |
| 2 | Pueblo Family Physicians ( Site 5606) | Phoenix | Arizona | United States | 85015 |
| 3 | Ruane Clinical Research Group, Inc. ( Site 5624) | Los Angeles | California | United States | 90036 |
| 4 | Midway Immunology and Research ( Site 5622) | Fort Pierce | Florida | United States | 34982 |
| 5 | Floridian Clinical Research, LLC ( Site 5625) | Miami Lakes | Florida | United States | 33016 |
| 6 | The Kinder Medical Group ( Site 5615) | Miami | Florida | United States | 33133 |
| 7 | Orlando Immunology Center ( Site 5613) | Orlando | Florida | United States | 32803 |
| 8 | CAN Community Health ( Site 5627) | Sarasota | Florida | United States | 34237 |
| 9 | Triple O Research Institute, P.A. ( Site 5621) | West Palm Beach | Florida | United States | 33407 |
| 10 | Columbus Regional Research Institute ( Site 5616) | Columbus | Georgia | United States | 31904 |
| 11 | Infectious Disease Specialists Of Atlanta PC ( Site 5608) | Decatur | Georgia | United States | 30033 |
| 12 | Hennepin Healthcare-Hennepin Healthcare-ID ( Site 5633) | Minneapolis | Minnesota | United States | 55415 |
| 13 | Kansas City CARE Clinic ( Site 5607) | Kansas City | Missouri | United States | 64111 |
| 14 | University of Pennsylvania ( Site 5630) | Philadelphia | Pennsylvania | United States | 19104 |
| 15 | Saint Hope Foundation, Inc. ( Site 5629) | Bellaire | Texas | United States | 77401 |
| 16 | North Texas ID Consultants, PA ( Site 5604) | Dallas | Texas | United States | 75246 |
| 17 | Texas Centers for Infectious Disease Associates P.A. ( Site 5619) | Fort Worth | Texas | United States | 76104 |
| 18 | IDEAA Foundation ( Site 5807) | Buenos Aires | Caba | Argentina | C1405CKC |
| 19 | Fundación Huesped ( Site 5801) | C.a.b.a | Caba | Argentina | C1202ABB |
| 20 | Helios Salud S.A. ( Site 5802) | Ciudad Autonoma de Buenos Aires | Caba | Argentina | C1141ACG |
| 21 | Instituto CAICI ( Site 5803) | Rosario | Santa Fe | Argentina | S2000PBJ |
| 22 | Instituto Oulton ( Site 5804) | Cordoba | Argentina | X5000JJS | |
| 23 | Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 5703) | Hamilton | Ontario | Canada | L8S 14K |
| 24 | Toronto General Hospital - University Health Network ( Site 5705) | Toronto | Ontario | Canada | M5G 2N2 |
| 25 | Clinique Medicale L Actuel ( Site 5714) | Montreal | Quebec | Canada | H2L 4P9 |
| 26 | McGill University Health Center - Research Institute-CVIS Clinical Research Unit ( Site 5702) | Montreal | Quebec | Canada | H4A 3J1 |
| 27 | Hospital Dr. Hernan Henriquez Aravena ( Site 5905) | Temuco | Araucania | Chile | 4781151 |
| 28 | Clinica Universidad Catolica del Maule ( Site 5909) | Talca | Maule | Chile | 3460000 |
| 29 | Clinica Arauco Salud ( Site 5900) | Santiago | Region M. De Santiago | Chile | 7560994 |
| 30 | Hospital Clinico de la Universidad Catolica ( Site 5903) | Santiago | Region M. De Santiago | Chile | 8331150 |
| 31 | Fundacion Arriaran ( Site 5901) | Santiago | Region M. De Santiago | Chile | 8360159 |
| 32 | Centro Cardiovascular Cardiosur ( Site 5907) | Santiago | Region M. De Santiago | Chile | 8910259 |
| 33 | Hospital Universitario San Ignacio ( Site 6005) | Bogota | Distrito Capital De Bogota | Colombia | 110231 |
| 34 | Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 6006) | Bogota | Distrito Capital De Bogota | Colombia | 111321 |
| 35 | Fundacion Valle del Lili ( Site 6001) | Cali | Valle Del Cauca | Colombia | 760032 |
| 36 | A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 6124) | Paris | Ain | France | 75018 |
| 37 | Centre Hospitalier Regional du Orleans ( Site 6108) | Orleans | Centre | France | 45000 |
| 38 | Hopital Francois Mitterrand ( Site 6119) | Dijon | Cote-d Or | France | 21079 |
| 39 | CHU de Bordeaux. Hopital Pellegrin ( Site 6116) | Bordeaux | Gironde | France | 33076 |
| 40 | Centre Hospitalier de Tourcoing ( Site 6100) | Tourcoing | Nord | France | 59208 |
| 41 | Hopital de la Croix-Rousse ( Site 6127) | Lyon | Rhone-Alpes | France | 69004 |
| 42 | Hopital Avicenne ( Site 6102) | Bobigny | Seine-Saint-Denis | France | 93000 |
| 43 | A.P.H. Paris, Hopital Saint Louis ( Site 6114) | Paris | France | 75010 | |
| 44 | Hopital Saint-Antoine ( Site 6113) | Paris | France | 75012 | |
| 45 | Hopital Pitie Salpetriere ( Site 6111) | Paris | France | 75013 | |
| 46 | Universitaetsklinik Freiburg ( Site 6206) | Freiburg | Baden-Wurttemberg | Germany | 79106 |
| 47 | Klinikum der LMU München ( Site 6204) | Muenchen | Bayern | Germany | 80336 |
| 48 | MVZ Munchen am Goetheplatz ( Site 6202) | Muenchen | Bayern | Germany | 80337 |
| 49 | Infektiologikum ( Site 6201) | Frankfurt am Main | Hessen | Germany | 60596 |
| 50 | Universitaetsklinikum Bonn ( Site 6200) | Bonn | Nordrhein-Westfalen | Germany | 53127 |
| 51 | EPIMED- Ges. f. epidemiolog. u. klin. Forschung in der Medizin mbH ( Site 6208) | Berlin | Germany | 10787 | |
| 52 | Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 6210) | Hamburg | Germany | 20246 | |
| 53 | Rambam Medical Center ( Site 6701) | Haifa | Israel | 3109601 | |
| 54 | Hadassah Ein Kerem Medical Center ( Site 6702) | Jerusalem | Israel | 9112001 | |
| 55 | Chaim Sheba Medical Center. ( Site 6704) | Ramat-Gan | Israel | 5265601 | |
| 56 | Kaplan Medical Center ( Site 6700) | Rehovot | Israel | 7610001 | |
| 57 | Sourasky Medical Center ( Site 6705) | Tel Aviv | Israel | 64239 | |
| 58 | A.O.R.N. dei Colli - Ospedale Cotugno ( Site 6407) | Napoli | Campania | Italy | 80131 |
| 59 | Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 6404) | Modena | Emilia-Romagna | Italy | 41124 |
| 60 | ASST Papa Giovanni XXIII ( Site 6411) | Bergamo | Lombardia | Italy | 24127 |
| 61 | Ospedale San Gerardo ASST Monza ( Site 6412) | Monza | Monza E Brianza | Italy | 20900 |
| 62 | Ospedale Amedeo di Savoia ( Site 6414) | Torino | Piemonte | Italy | 10149 |
| 63 | Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 6401) | Milano | Italy | 20122 | |
| 64 | Salute San Raffaele ( Site 6402) | Milano | Italy | 20127 | |
| 65 | Azienda Ospedaliera San Paolo ( Site 6403) | Milano | Italy | 20142 | |
| 66 | ASST Fatebenefratelli-Ospedale Sacco ( Site 6400) | Milano | Italy | 20157 | |
| 67 | IRCCS Policlinico San Matteo ( Site 6410) | Pavia | Italy | 27100 | |
| 68 | Azienda USL di Pescara-Presidio Ospedaliero di Pescara ( Site 6413) | Pescara | Italy | 65129 | |
| 69 | Istituto Nazionale per Le Malattie Infettive Lazzaro Spallanzani ( Site 6405) | Roma | Italy | 00149 | |
| 70 | National Hospital Organization Nagoya Medical Center ( Site 6903) | Nagoya | Aichi | Japan | 460-0001 |
| 71 | Kumamoto University Hospital ( Site 6905) | Kumamoto | Japan | 860-8556 | |
| 72 | National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 69 | Osaka | Japan | 540-0006 | |
| 73 | Tokyo Medical University Hospital ( Site 6904) | Tokyo | Japan | 160-0023 | |
| 74 | Center Hospital of the National Center for Global Health and Medicine ( Site 6901) | Tokyo | Japan | 162-8655 | |
| 75 | JOSHA Research ( Site 6605) | Bloemfontein | Free State | South Africa | 9301 |
| 76 | Chris Hani Baragwanath Hospital - ICU ( Site 6608) | Johannesburg | Gauteng | South Africa | 1862 |
| 77 | Wits Health Consortium. Clinical HIV Research Unit ( Site 6614) | Johannesburg | Gauteng | South Africa | 2041 |
| 78 | Ezintsha ( Site 6609) | Johannesburg | Gauteng | South Africa | 2193 |
| 79 | Wentworth Hospital ( Site 6607) | Durban | Kwazulu-Natal | South Africa | 4052 |
| 80 | Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 6617) | Cape Town | Western Cape | South Africa | 7500 |
| 81 | Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 6613) | Cape Town | Western Cape | South Africa | 7925 |
| 82 | Be Part Yoluntu Centre ( Site 6603) | Mbekweni, Paarl | Western Cape | South Africa | 7646 |
| 83 | Hospital General de Elche ( Site 6308) | Elche | Alicante | Spain | 03202 |
| 84 | Hospital Universitari Germans Trias i Pujol ( Site 6301) | Badalona | Barcelona | Spain | 08916 |
| 85 | Hospital Universitari de Bellvitge ( Site 6312) | LHospitalet de Llobregat | Barcelona | Spain | 08907 |
| 86 | Hospital Vall D Hebron ( Site 6302) | Barcelona | Cataluna | Spain | 08035 |
| 87 | Hospital Clinic i Provincial ( Site 6300) | Barcelona | Cataluna | Spain | 08036 |
| 88 | Hospital General Universitario Gregorio Maranon ( Site 6303) | Madrid | Spain | 28007 | |
| 89 | Hospital Universitario Fundacion Jimenez Diaz ( Site 6307) | Madrid | Spain | 28040 | |
| 90 | Hospital Universitario 12 de Octubre ( Site 6305) | Madrid | Spain | 28041 | |
| 91 | Hospital Universitario La Paz ( Site 6304) | Madrid | Spain | 28046 | |
| 92 | Hospital Universitario Virgen de la Victoria ( Site 6309) | Malaga | Spain | 29010 | |
| 93 | Kaohsiung Veterans General Hospital ( Site 7102) | Kaohsiung | Taiwan | 81362 | |
| 94 | National Cheng Kung University Hospital ( Site 7101) | Tainan | Taiwan | 70403 | |
| 95 | National Taiwan University Hospital ( Site 7100) | Taipei | Taiwan | 100 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 8591A-020
- MK-8591A-020
- jRCT2031210024
- 2019-000590-23