HIV-1 InfectionPhase 3NCT04233879
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)
A Phase 3 study testing DOR/ISL and BIC/FTC/TAF in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC at 95 sites in 13 countries.
Trial 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 living with human immunodeficiency virus type-1 (HIV-1) infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- DOR/ISL and BIC/FTC/TAF
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 599 participants
- Where
- 95 sitesin 13 countries
- Study dates
- 28 Feb 2020to 29 Jan 2025
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Has human immunodeficiency virus type 2 (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 hepatitis B virus (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
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- 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
Trial locations and contacts
95 sites in 13 countries.
95 sites in 13 countries
United States17 sites
Saint Hope Foundation, Inc. ( Site 5629)
Bellaire, Texas, 77401
University of Alabama at Birmingham 1917 Research Clinic ( Site 5610)
Birmingham, Alabama, 35222
Columbus Regional Research Institute ( Site 5616)
Columbus, Georgia, 31904
North Texas ID Consultants, PA ( Site 5604)
Dallas, Texas, 75246
Infectious Disease Specialists Of Atlanta PC ( Site 5608)
Decatur, Georgia, 30033
Texas Centers for Infectious Disease Associates P.A. ( Site 5619)
Fort Worth, Texas, 76104
Midway Immunology and Research ( Site 5622)
Ft. Pierce, Florida, 34982
Kansas City CARE Clinic ( Site 5607)
Kansas City, Missouri, 64111
Ruane Clinical Research Group, Inc. ( Site 5624)
Los Angeles, California, 90036
The Kinder Medical Group ( Site 5615)
Miami, Florida, 33133
Floridian Clinical Research, LLC ( Site 5625)
Miami Lakes, Florida, 33016
Hennepin Healthcare-Hennepin Healthcare-ID ( Site 5633)
Minneapolis, Minnesota, 55415
Orlando Immunology Center ( Site 5613)
Orlando, Florida, 32803
University of Pennsylvania ( Site 5630)
Philadelphia, Pennsylvania, 19104
Pueblo Family Physicians ( Site 5606)
Phoenix, Arizona, 85015
CAN Community Health ( Site 5627)
Sarasota, Florida, 34237
Triple O Research Institute, P.A. ( Site 5621)
West Palm Beach, Florida, 33407
Italy12 sites
ASST Papa Giovanni XXIII ( Site 6411)
Bergamo, Lombardy, 24127
Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 6401)
Milan, 20122
Salute San Raffaele ( Site 6402)
Milan, 20127
Azienda Ospedaliera San Paolo ( Site 6403)
Milan, 20142
ASST Fatebenefratelli-Ospedale Sacco ( Site 6400)
Milan, 20157
Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 6404)
Modena, Emilia-Romagna, 41124
Ospedale San Gerardo ASST Monza ( Site 6412)
Monza, Monza E Brianza, 20900
A.O.R.N. dei Colli - Ospedale Cotugno ( Site 6407)
Naples, Campania, 80131
IRCCS Policlinico San Matteo ( Site 6410)
Pavia, 27100
Azienda USL di Pescara-Presidio Ospedaliero di Pescara ( Site 6413)
Pescara, 65129
Istituto Nazionale per Le Malattie Infettive Lazzaro Spallanzani ( Site 6405)
Roma, 00149
Ospedale Amedeo di Savoia ( Site 6414)
Turin, Piedmont, 10149
France10 sites
Hopital Avicenne ( Site 6102)
Bobigny, Seine-Saint-Denis, 93000
CHU de Bordeaux. Hopital Pellegrin ( Site 6116)
Bordeaux, Gironde, 33076
Hopital Francois Mitterrand ( Site 6119)
Dijon, Cote-d Or, 21079
Hopital de la Croix-Rousse ( Site 6127)
Lyon, Auvergne-Rhône-Alpes, 69004
Centre Hospitalier Regional du Orleans ( Site 6108)
Orléans, Centre-Val de Loire, 45000
A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 6124)
Paris, Ain, 75018
A.P.H. Paris, Hopital Saint Louis ( Site 6114)
Paris, 75010
Hopital Saint-Antoine ( Site 6113)
Paris, 75012
Hopital Pitie Salpetriere ( Site 6111)
Paris, 75013
Centre Hospitalier de Tourcoing ( Site 6100)
Tourcoing, Nord, 59208
Spain10 sites
Hospital Universitari Germans Trias i Pujol ( Site 6301)
Badalona, Barcelona, 08916
Hospital Vall D Hebron ( Site 6302)
Barcelona, Catalonia, 08035
Hospital Clinic i Provincial ( Site 6300)
Barcelona, Catalonia, 08036
Hospital General de Elche ( Site 6308)
Elche, Alicante, 03202
Hospital Universitari de Bellvitge ( Site 6312)
LHospitalet de Llobregat, Barcelona, 08907
Hospital General Universitario Gregorio Maranon ( Site 6303)
Madrid, 28007
Hospital Universitario Fundacion Jimenez Diaz ( Site 6307)
Madrid, 28040
Hospital Universitario 12 de Octubre ( Site 6305)
Madrid, 28041
Hospital Universitario La Paz ( Site 6304)
Madrid, 28046
Hospital Universitario Virgen de la Victoria ( Site 6309)
Málaga, 29010
South Africa8 sites
JOSHA Research ( Site 6605)
Bloemfontein, Free State, 9301
Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 6617)
Cape Town, Western Cape, 7500
Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 6613)
Cape Town, Western Cape, 7925
Wentworth Hospital ( Site 6607)
Durban, KwaZulu-Natal, 4052
Chris Hani Baragwanath Hospital - ICU ( Site 6608)
Johannesburg, Gauteng, 1862
Wits Health Consortium. Clinical HIV Research Unit ( Site 6614)
Johannesburg, Gauteng, 2041
Ezintsha ( Site 6609)
Johannesburg, Gauteng, 2193
Be Part Yoluntu Centre ( Site 6603)
Mbekweni, Paarl, Western Cape, 7646
Germany7 sites
EPIMED- Ges. f. epidemiolog. u. klin. Forschung in der Medizin mbH ( Site 6208)
Berlin, 10787
Universitaetsklinikum Bonn ( Site 6200)
Bonn, North Rhine-Westphalia, 53127
Infektiologikum ( Site 6201)
Frankfurt am Main, Hesse, 60596
Universitaetsklinik Freiburg ( Site 6206)
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 6210)
Hamburg, 20246
Klinikum der LMU München ( Site 6204)
Munich, Bavaria, 80336
MVZ Munchen am Goetheplatz ( Site 6202)
Munich, Bavaria, 80337
Chile6 sites
Clinica Arauco Salud ( Site 5900)
Santiago, Region M. de Santiago, 7560994
Hospital Clinico de la Universidad Catolica ( Site 5903)
Santiago, Region M. de Santiago, 8331150
Fundacion Arriaran ( Site 5901)
Santiago, Region M. de Santiago, 8360159
Centro Cardiovascular Cardiosur ( Site 5907)
Santiago, Region M. de Santiago, 8910259
Clinica Universidad Catolica del Maule ( Site 5909)
Talca, Maule Region, 3460000
Hospital Dr. Hernan Henriquez Aravena ( Site 5905)
Temuco, Araucania, 4781151
Argentina5 sites
Helios Salud S.A. ( Site 5802)
Buenos Aires, Buenos Aires F.D., C1141ACG
IDEAA Foundation ( Site 5807)
Buenos Aires, Buenos Aires F.D., C1405CKC
Fundación Huesped ( Site 5801)
C.a.b.a, Buenos Aires F.D., C1202ABB
Instituto Oulton ( Site 5804)
Córdoba, X5000JJS
Instituto CAICI ( Site 5803)
Rosario, Santa Fe Province, S2000PBJ
Israel5 sites
Rambam Medical Center ( Site 6701)
Haifa, 3109601
Hadassah Ein Kerem Medical Center ( Site 6702)
Jerusalem, 9112001
Chaim Sheba Medical Center. ( Site 6704)
Ramat Gan, 5265601
Kaplan Medical Center ( Site 6700)
Rehovot, 7610001
Sourasky Medical Center ( Site 6705)
Tel Aviv, 64239
Japan5 sites
Kumamoto University Hospital ( Site 6905)
Kumamoto, 860-8556
National Hospital Organization Nagoya Medical Center ( Site 6903)
Nagoya, Aichi-ken, 460-0001
National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 69
Osaka, 540-0006
Tokyo Medical University Hospital ( Site 6904)
Tokyo, 160-0023
Center Hospital of the National Center for Global Health and Medicine ( Site 6901)
Tokyo, 162-8655
Canada4 sites
Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 5703)
Hamilton, Ontario, L8S 14K
Clinique Medicale L Actuel ( Site 5714)
Montreal, Quebec, H2L 4P9
McGill University Health Center - Research Institute-CVIS Clinical Research Unit ( Site 5702)
Montreal, Quebec, H4A 3J1
Toronto General Hospital - University Health Network ( Site 5705)
Toronto, Ontario, M5G 2N2
Colombia3 sites
Hospital Universitario San Ignacio ( Site 6005)
Bogotá, Bogota D.C., 110231
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 6006)
Bogotá, Bogota D.C., 111321
Fundacion Valle del Lili ( Site 6001)
Cali, Valle del Cauca Department, 760032
Taiwan3 sites
Kaohsiung Veterans General Hospital ( Site 7102)
Kaohsiung City, 81362
National Cheng Kung University Hospital ( Site 7101)
Tainan, 70403
National Taiwan University Hospital ( Site 7100)
Taipei, 100
About this study
Official title: A Phase 3 Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir Once-Daily in HIV-1 Infected Treatment-Naïve Participants
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 living 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.
Read the 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).
- Conditions
- HIV-1 Infection
- Being tested
- DOR/ISL, BIC/FTC/TAF, Placebo to BIC/FTC/TAF, Placebo to DOR/ISL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DOR/ISLDrug
Also called MK-8591A, Doravirine/islatravir
100 mg DOR/0.75 mg ISL FDC single tablet taken once daily by mouth.
BIC/FTC/TAFDrug
Also called Bictegravir/emtricitabine/tenofovir alafenamide
BIC/FTC/TAF 50/200/25 mg FDC single tablet taken once daily by mouth.
Placebo to BIC/FTC/TAFDrug
Placebo single tablet matched to BIC/FTC/TAF taken by mouth.
Placebo to DOR/ISLDrug
Placebo single tablet matched to DOR/ISL taken by mouth.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: doravirine/islatravir (DOR/ISL) | Experimental | Treatment-naïve participants living with human immunodeficiency virus-1 (HIV-1) that had not received ≤10 days of prior antiretroviral therapy received blinded fixed dose combination (FDC) Doravirine/Islatravir (DOR/ISL) (100 mg doravirine [DOR]/0.75 mg islatravir [ISL]) and placebo to Bictegravir/Tenofovir Alafenamide/Emtricitabine (BIC/FTC/TAF) once daily (QD) from Day 1 to Week 96, and open-label DOR/ISL up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive open-label QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168. Receives: Drug: DOR/ISL; Drug: Placebo to BIC/FTC/TAF |
| Group 2: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) | Active comparator | Treatment-naïve participants living with HIV-1 that had not received ≤10 days of prior antiretroviral therapy received blinded BIC/FTC/TAF (50 mg bictegravir [BIC], 200 mg emtricitabine [FTC], 25 mg tenofovir alafenamide [TAF]) and placebo to FDC DOR/ISL QD from Day 1 to Week 96, and open-label BIC/FTC/TAF up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168. Receives: Drug: BIC/FTC/TAF; Drug: Placebo to DOR/ISL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
The Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 was presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The final analysis for this outcome is presented here.
Measured: Week 48
Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48
An AE was 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 experienced at least one AE up to Week 48 was reported. The final analysis for this outcome is presented here.
Measured: Up to approximately 48 weeks
Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48
An AE was 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 up to Week 48 were reported. The final analysis for this outcome is presented here.
Measured: Up to approximately 48 weeks
Secondary outcomes (19)
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.
Measured: Week 96
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144
The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 144 was presented using the Data as Observed (DAO) missing data approach. The final analysis for this outcome is presented here.
Measured: Week 144
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48
The percentage of participants with HIV-1 RNA <40 copies/mL was determined. The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 48 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.
Measured: Week 48
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48
The percentage of participants with HIV-1 RNA <200 copies/mL was determined. The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.
Measured: Week 48
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96
The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.
Measured: Week 96
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96
The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.
Measured: Week 96
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144
The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 144 was presented using the DAO missing data approach. The final analysis for this outcome is presented here.
Measured: Week 144
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144
The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 144 was presented using the DAO missing data approach. The final analysis for this outcome is presented here.
Measured: Week 144
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48
Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and at Week 48 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 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here.
Measured: Baseline (Day 1) and Week 48
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 96
Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and at Week 96 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 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here.
Measured: Baseline (Day 1) and Week 96
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 144
Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and at Week 144 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 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here.
Measured: Baseline (Day 1) and Week 144
Incidence of Viral Resistance-Associated Substitutions (RASs) at 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. The final analysis for this outcome is presented here.
Measured: Week 48
Incidence of Viral RASs at 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 demonstrated RASs at Week 96 was presented. The final analysis for this outcome is presented here.
Measured: Week 96
Incidence of Viral RASs at 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 demonstrated RASs at Week 144 was presented. The final analysis for this outcome is presented here.
Measured: Week 144
Mean Change From Baseline in Body Weight at Week 48
Body weight was measured at baseline and at Week 48. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 48 was presented. The final analysis for this outcome is presented here.
Measured: Baseline (Day 1) and Week 48
Mean Change From Baseline in Body Weight at Week 96
Body weight was measured at baseline and at Week 96. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 96 was presented. The final analysis for this outcome is presented here.
Measured: Baseline (Day 1) and Week 96
Mean Change From Baseline in Body Weight at Week 144
Body weight was measured at baseline and at Week 144. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 144 was presented. The final analysis for this outcome is presented here.
Measured: Baseline (Day 1) and Week 144
Percentage of Participants Who Experienced an Adverse Event (AE)
An AE was 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 experienced at least one or more AEs is presented. Per protocol, pregnancy-related AEs collected for enrolled participants are reported separately and are presented in the AE module. The final analysis for this outcome is presented here.
Measured: Up to approximately 47 months
Percentage of Participants Who Discontinued Study Treatment Due to an AE
An AE was 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 intervention due to an AE is presented. Per protocol, pregnancy-related AEs collected for enrolled participants are reported separately and are presented in the AE module. The final analysis for this outcome is presented here.
Measured: Up to approximately 38 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start28 Feb 2020
- Primary completion17 Nov 2022
- Study completion29 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 599 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04233879
- Sponsor's protocol ID
- 8591A-020
- Other IDs
- MK-8591A-020, jRCT2031210024, 2019-000590-23, 2019
- Status last verified
- Jun 2026
- First submitted
- 15 Jan 2020
- Last updated
- 3 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Rockstroh JK, Paredes R, Cahn P, Molina JM, Sokhela SM, Hinestrosa F, Kassim S, Cunningham D, Ghosn J, Bogner JR, Gatanaga H, Asante-Appiah E, Zhang Y, Nwoke U, Klopfer SO, Eves K, Squires K, Correll T, Fox MC, Pisculli ML. Doravirine/Islatravir (100/0.75 mg) Once-Daily Compared With Bictegravir/Emtricitabine/Tenofovir Alafenamide as Initial HIV-1 Treatment: 48-Week Results From a Phase 3, Randomized, Controlled, Double-Blind, Noninferiority Trial. Clin Infect Dis. 2025 Sep 16;81(2):322-332. doi: 10.1093/cid/ciaf077.
PubMed 40079835
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir Once-Daily in HIV-1 Infected Treatment-Naïve Participants
- ClinicalTrials.gov ID
- NCT04233879
- Acronym / sponsor ID
- 8591A-020
- Conditions
- HIV-1 Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 599 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 28 Feb 2020 (actual)
- Primary completion
- 17 Nov 2022 (actual)
- Study completion
- 29 Jan 2025 (actual)
- First posted
- 18 Jan 2020 (actual)
- Results
- Posted 21 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 living 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: doravirine/islatravir (DOR/ISL) | Experimental | Drug: DOR/ISL, Drug: Placebo to BIC/FTC/TAFTreatment-naïve participants living with human immunodeficiency virus-1 (HIV-1) that had not received ≤10 days of prior antiretroviral therapy received blinded fixed dose combination (FDC) Doravirine/Islatravir (DOR/ISL) (100 mg doravirine [DOR]/0.75 mg islatravir [ISL]) and placebo to Bictegravir/Tenofovir Alafenamide/Emtricitabine (BIC/FTC/TAF) once daily (QD) from Day 1 to Week 96, and open-label DOR/ISL up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive open-label QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168. |
| Group 2: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) | Active comparator | Drug: BIC/FTC/TAF, Drug: Placebo to DOR/ISLTreatment-naïve participants living with HIV-1 that had not received ≤10 days of prior antiretroviral therapy received blinded BIC/FTC/TAF (50 mg bictegravir [BIC], 200 mg emtricitabine [FTC], 25 mg tenofovir alafenamide [TAF]) and placebo to FDC DOR/ISL QD from Day 1 to Week 96, and open-label BIC/FTC/TAF up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- Has human immunodeficiency virus type 2 (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 hepatitis B virus (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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DOR/ISLAlso: MK-8591A, Doravirine/islatravir100 mg DOR/0.75 mg ISL FDC single tablet taken once daily by mouth. | Drug | Group 1: doravirine/islatravir (DOR/ISL) |
| BIC/FTC/TAFAlso: Bictegravir/emtricitabine/tenofovir alafenamideBIC/FTC/TAF 50/200/25 mg FDC single tablet taken once daily by mouth. | Drug | Group 2: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) |
| Placebo to BIC/FTC/TAFPlacebo single tablet matched to BIC/FTC/TAF taken by mouth. | Drug | Group 1: doravirine/islatravir (DOR/ISL) |
| Placebo to DOR/ISLPlacebo single tablet matched to DOR/ISL taken by mouth. | Drug | Group 2: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) |
Primary outcome
Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
Time frame: Week 48
The Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 was presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The final analysis for this outcome is presented here.
Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48
Time frame: Up to approximately 48 weeks
An AE was 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 experienced at least one AE up to Week 48 was reported. The final analysis for this outcome is presented here.
Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48
Time frame: Up to approximately 48 weeks
An AE was 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 up to Week 48 were reported. The final analysis for this outcome is presented here.
19 secondary outcomes
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
Time frame: Week 96
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144
Time frame: Week 144
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48
Time frame: Week 48
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48
Time frame: Week 48
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96
Time frame: Week 96
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96
Time frame: Week 96
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144
Time frame: Week 144
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144
Time frame: Week 144
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48
Time frame: Baseline (Day 1) and Week 48
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 96
Time frame: Baseline (Day 1) and Week 96
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 144
Time frame: Baseline (Day 1) and Week 144
Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48
Time frame: Week 48
Incidence of Viral RASs at Week 96
Time frame: Week 96
Incidence of Viral RASs at Week 144
Time frame: Week 144
Mean Change From Baseline in Body Weight at Week 48
Time frame: Baseline (Day 1) and Week 48
Mean Change From Baseline in Body Weight at Week 96
Time frame: Baseline (Day 1) and Week 96
Mean Change From Baseline in Body Weight at Week 144
Time frame: Baseline (Day 1) and Week 144
Percentage of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to approximately 47 months
Percentage of Participants Who Discontinued Study Treatment Due to an AE
Time frame: Up to approximately 38 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 40079835Rockstroh JK, Paredes R, Cahn P, Molina JM, Sokhela SM, Hinestrosa F, Kassim S, Cunningham D, Ghosn J, Bogner JR, Gatanaga H, Asante-Appiah E, Zhang Y, Nwoke U, Klopfer SO, Eves K, Squires K, Correll T, Fox MC, Pisculli ML. Doravirine/Islatravir (100/0.75 mg) Once-Daily Compared With Bictegravir/Emtricitabine/Tenofovir Alafenamide as Initial HIV-1 Treatment: 48-Week Results From a Phase 3, Randomized, Controlled, Double-Blind, Noninferiority Trial. Clin Infect Dis. 2025 Sep 16;81(2):322-332. doi: 10.1093/cid/ciaf077.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Plain Language SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
95 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing DOR/ISL and BIC/FTC/TAF in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC at 95 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 95 sites in United States, Italy, France, Spain, South Africa and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 (time frame: Week 48). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04233879, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.