HIV InfectionPhase 3NCT04223778
Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017)
A Phase 3 study testing DOR/ISL and ART in people with HIV Infection, run by Merck Sharp & Dohme LLC at 78 sites in 15 countries.
Trial summary
This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- DOR/ISL and ART
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 672 participants
- Where
- 78 sitesin 15 countries
- Study dates
- 18 Feb 2020to 26 Aug 2024
- 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 (HIV-1) positive
- Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen.
- Females are eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP); is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle; 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; if a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
Who cannot join
- 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 Hepatitis B Virus (HBV) co-infection
- 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
- Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
- Is currently taking long-acting cabotegravir-rilpivirine
Show all 9Show fewer
- 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 treatment period
- Has a documented or known virologic resistance to doravirine (DOR)
- Expects to conceive or donate eggs at any time during the study
Trial locations and contacts
78 sites in 15 countries.
78 sites in 15 countries
United States15 sites
Saint Hope Foundation, Inc. ( Site 1037)
Bellaire, Texas, 77401
University of North Carolina at Chapel Hill ( Site 1042)
Chapel Hill, North Carolina, 27599
Northstar Healthcare ( Site 1002)
Chicago, Illinois, 60657
North Texas ID Consultants, PA ( Site 1003)
Dallas, Texas, 75246
Texas Centers for Infectious Disease Associates P.A. ( Site 1022)
Fort Worth, Texas, 76104
Midway Immunology and Research ( Site 1030)
Ft. Pierce, Florida, 34982
ID Care ( Site 1023)
Hillsborough, New Jersey, 08844
The Crofoot Research Center, Inc. ( Site 1005)
Houston, Texas, 77098
Kansas City CARE Health Center ( Site 1008)
Kansas City, Missouri, 64111
Orlando Immunology Center ( Site 1007)
Orlando, Florida, 32803
Bliss Healthcare Services ( Site 1025)
Orlando, Florida, 32806
University of Pennsylvania ( Site 1038)
Philadelphia, Pennsylvania, 19104
Chatham County Health Department ( Site 1043)
Savannah, Georgia, 31401
Georgetown University Hospital ( Site 1018)
Washington D.C., District of Columbia, 20007
Triple O Research Institute, P.A. ( Site 1026)
West Palm Beach, Florida, 33407
Russia8 sites
Republican Clinical Hospital of Infectious Diseases n. a. A.F.Agafonov ( Site 1707)
Kazan', Tatarstan, Respublika, 420140
Kemerovo Regional Center for the Prevention and Control of AIDS ( Site 1713)
Kemerovo, Kemerovo Oblast, 650056
Krasnoyarsk Regional Center for Prevention and Control of AIDS ( Site 1712)
Krasnoyarsk, Krasnoyarsk Krai, 660049
Federal Scientific Methodological AIDS Prevention and Control Center ( Site 1703)
Moscow, Moscow, 105275
Infectious Clinical Hospital #2 ( Site 1719)
Moscow, Moscow, 105275
Saint Petersburg Center for Prophylactic of AIDS and Inf. Diseases ( Site 1701)
Saint Petersburg, Leningradskaya Oblast', 190020
FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 1700)
Saint Petersburg, Sankt-Peterburg, 196645
Regional Center for Prevent. and Control of AIDS and Inf. Diseases ( Site 1715)
Yekaterinburg, Sverdlovsk Oblast, 620102
Canada7 sites
Southern Alberta HIV Clinic ( Site 1108)
Calgary, Alberta, T2R 0X7
Hamilton Health Sciences ( Site 1103)
Hamilton, Ontario, L8L 2X2
Clinique de Medecine Urbaine du Quartier Latin ( Site 1104)
Montreal, Quebec, H2L 4E9
Clinique Medicale L Actuel ( Site 1114)
Montreal, Quebec, H2L 4P9
Maple Leaf Research ( Site 1112)
Toronto, Ontario, M5G 1K2
Toronto General Hospital - University Health Network ( Site 1105)
Toronto, Ontario, M5G 2N2
Vancouver ID Research and Care Centre Society ( Site 1100)
Vancouver, British Columbia, V6Z 2C7
France7 sites
CHU de Bordeaux- Hopital Saint Andre ( Site 2015)
Bordeaux, Gironde, 33075
Hopital Francois Mitterrand ( Site 2019)
Dijon, Cote-d'Or, 21079
Hopital de la Croix-Rousse ( Site 2027)
Lyon, Auvergne-Rhône-Alpes, 69317
CHU Hotel Dieu Nantes ( Site 2020)
Nantes, Loire-Atlantique, 44093
A.P.H. Paris, Hopital Saint Louis ( Site 2014)
Paris, 75010
CHU de Rouen ( Site 2005)
Rouen, Seine-Maritime, 76031
CHU de Toulouse - Hopital Purpan ( Site 2004)
Toulouse, Haute-Garonne, 31059
Spain7 sites
Hospital Universitari Germans Trias i Pujol ( Site 1606)
Badalona, Barcelona [Barcelona], 08916
Hospital Clinic i Provincial ( Site 1600)
Barcelona, 08036
Hospital General de Elche ( Site 1608)
Elche, Alicante, 03202
Hospital General Universitario Gregorio Maranon ( Site 1603)
Madrid, 28007
Hospital Universitario Infanta Leonor ( Site 1601)
Madrid, 28031
Hospital Universitario Fundacion Jimenez Diaz ( Site 1602)
Madrid, 28040
Hospital Universitario La Paz ( Site 1604)
Madrid, 28046
Switzerland6 sites
Universitaetsspital Basel ( Site 3302)
Basel, Canton of Basel-City, 4031
Inselspital Universitaetsspital Bern ( Site 3303)
Bern, Canton of Bern, 3010
Hopitaux Universitaires de Geneve HUG. ( Site 3304)
Geneva, Canton of Geneva, 1211
Ospedale Regionale di Lugano Civico ( Site 3305)
Lugano, Canton Ticino, 6903
Kantonsspital St. Gallen ( Site 3301)
Sankt Gallen, Canton of St. Gallen, 9007
Universitaetsspital Zuerich ( Site 3300)
Zurich, Canton of Zurich, 8091
Japan5 sites
National Hospital Organization Nagoya Medical Center ( Site 2403)
Nagoya, Aichi-ken, 460-0001
National Hospital Organization Osaka National Hospital ( Site 2402)
Osaka, 540-0006
Tokyo Metropolitan Komagome Hospital ( Site 2406)
Tokyo, 113-8677
Tokyo Medical University Hospital ( Site 2404)
Tokyo, 160-0023
Center Hospital of the National Center for Global Health and Medicine ( Site 2401)
Tokyo, 162-8655
United Kingdom5 sites
Brighton and Sussex University Hospital NHS Trust ( Site 1908)
Brighton, Brighton And Hove, BN2 1ES
Southmead Hospital ( Site 1910)
Bristol, Bristol, City of, BS10 5NB
Royal Free Hospital ( Site 1904)
London, Camden, NW3 2QG
Kings College Hospital NHS Foundation Trust ( Site 1907)
London, London, City of, SE5 9RJ
North Manchester General Hospital ( Site 1902)
Manchester, M8 5RB
Australia4 sites
Melbourne Sexual Health Centre ( Site 2305)
Carlton, Victoria, 3053
Royal Brisbane and Womens Hospital- Infectious Diseases Unit ( Site 2309)
Herston, Queensland, 4029
Fiona Stanley Hospital ( Site 2301)
Murdoch, Western Australia, 6150
Holdsworth House Medical Practice ( Site 2300)
Sydney, New South Wales, 2010
Poland4 sites
Wojewodzki Szpital Specjalistyczny im. dr. Wladyslawa Bieganskiego ( Site 1503)
Lodz-Baluty, Łódź Voivodeship, 91-347
SP ZOZ Wojewodzki Szpital Zakazny ( Site 1505)
Warsaw, Masovian Voivodeship, 01-201
EMC Instytut Medyczny SA Przychodnia przy ul. Lowieckiej we Wroclawiu ( Site 1500)
Wroclaw, Lower Silesian Voivodeship, 50-220
Wroclawskie Centrum Zdrowia SP ZOZ ( Site 1507)
Wroclaw, 50-136
Chile3 sites
Clinica Arauco Salud ( Site 1300)
Santiago, Santiago Metropolitan, 7560994
Centro de Investigacion Clinica UC CICUC ( Site 1303)
Santiago, Santiago Metropolitan, 8330034
Hospital Dr. Hernan Henriquez Aravena ( Site 1305)
Temuco, Araucania, 4781151
Italy3 sites
ASST Fatebenefratelli-Ospedale Sacco ( Site 2200)
Milan, 20157
A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 2208)
Naples, 80131
Policlinico Gemelli Instituto di Clinica Chirurgica ( Site 2206)
Roma, 00168
South Africa2 sites
JOSHA Research ( Site 1406)
Bloemfontein, Free State, 9301
Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 1414)
Cape Town, Western Cape, 7925
Colombia1 site
Fundacion Valle del Lili ( Site 1201)
Cali, Valle del Cauca Department, 760032
New Zealand1 site
Christchurch Hospital ( Site 2303)
Christchurch, Canterbury, 8011
About this study
Official title: A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy
This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.
- Conditions
- HIV Infection
- Being tested
- DOR/ISL, ART
- Medical subject headings
- HIV Infections
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
A FDC of 100 mg DOR/ 0.75 mg ISL taken in tablet form, orally, once daily
ARTDrug
Baseline ART regimen will be administered as per approved label. ART medication will not be provided by the Sponsor; participants will provide their own ART medications. Allowed drug classes include nucleoside analog reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transferase inhibitors (InSTIs), fusion inhibitors, chemokine receptor 5 (CCR5) antagonists, post-attachment inhibitor, and pharmacokinetic (PK) boosters.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Experimental | Participants who were previously treated with continuous baseline antiretroviral therapy (ART) will receive DOR/ISL, a fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) orally once daily for 96 weeks. Receives: Drug: DOR/ISL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Active comparator | Participants received continuous baseline ART for 48 weeks. Continuing participants delayed switch over from baseline ART to DOR/ISL, fixed dose combination of 100 mg DOR/0.75 mg ISL orally once daily, from Week 48 to Week 96, a total DOR/ISL treatment duration of 48 Weeks. Receives: Drug: DOR/ISL; Drug: ART |
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
HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime 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 is presented using the FDA Snapshot missing data approach.
Measured: Week 48
Percentage of Participants With One or More Adverse Events (AEs) up to Week 48
An AE was defined as 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. The percentage of participants who experienced at least one AE was reported.
Measured: Up to ~48 Weeks
Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48
An AE was defined as 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. The percentage of participants who discontinued study intervention due to an AE was reported.
Measured: Up to ~48 Weeks
Secondary outcomes (19)
Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48
HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA <40 copies/mL or <50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
Measured: Week 48
Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96
HIV-1 RNA levels in blood samples taken at each visit was measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 is reported for Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 for Group 1 participants is a separate outcome measure and is presented later in the record.
Measured: Week 96
Group 1: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96
HIV-1 RNA levels in blood samples taken at each visit was measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 for Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96 is a separate outcome measure and is presented earlier in the record.
Measured: Week 96
Percentage Change From Baseline in CD4+ T-cell Count at Week 48
Plasma CD4+ T-Cell Count was measured in cells/mm^3 for baseline and 48 weeks. Baseline measurements were defined as the Day 1 value of each participant. The percentage change from baseline to Week 48 is presented.
Measured: Baseline and Week 48
Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96
Plasma CD4+ T-Cell Count was measured in cells/mm^3 for baseline and 96 weeks. Baseline measurements were defined as the Day 1 value of each participant. The mean percent change from baseline to Week 96 in CD4+ T-cell count is reported for Group 1 participants. Per protocol, the mean percentage change from baseline in CD4+ T-cell count at Week 96 for Group 2 participants was not planned or conducted.
Measured: Baseline and Week 96
Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96
Plasma CD4+ T-Cell Count was measured in cells/mm^3 for Week 48 and Week 96. The mean percent change from Week 48 to Week 96 is reported for Group 1 and Group 2 participants who delayed switch over from baseline ART to DOR/ISL Week 48 to Week 96.
Measured: Week 48 and Week 96
Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48
Viral drug resistance is defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The percentage of participants who demonstrated drug resistance at Week 48 is presented.
Measured: Week 48
Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96
Viral drug resistance was defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The percentage of participants who demonstrate drug resistance at Week 96 is presented for Group 1 and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. Per protocol, the percentage of participants with evidence of viral drug resistance-associated substitutions from week 0 to week 48 for Group 1 and Group 2 participants is a separate outcome measure and is presented earlier in the record.
Measured: Week 96
Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)
Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.
Measured: Baseline and Week 24
Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)
Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.
Measured: Baseline and Week 24
Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens
Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.
Measured: Baseline and Week 24
Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)
Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.
Measured: Baseline and Week 48
Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)
Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.
Measured: Baseline and Week 48
Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens
Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.
Measured: Baseline and Week 48
Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens)
Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight to Week 48 is presented for participants who received InSTI- based regimens.
Measured: Baseline and Week 48
Group 1: Percentage of Participants With One or More AEs up to Week 96
An AE was defined as 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. The percentage of participants who experienced at least one AE up to Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants with one or more AEs for Group 2 participants is a separate outcome measure and is presented later in the record.
Measured: Up to ~96 Weeks
Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96
An AE was defined as 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. The percentage of participants who discontinued study intervention due to an AE up to Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants who discontinued study intervention for Group 2 participants is a separate outcome measure and is presented later in the record.
Measured: Up to ~96 Weeks
Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96
An AE was defined as 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. The percentage of participants who experienced at least one AE from Week 48 up to Week 96 is reported for Group 1 participants and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.
Measured: Weeks 48-96 (up to ~48 weeks)
Group 1 & Group 2 (Switch-Over): Percentage of Participants Who Discontinued Study Intervention Due to an AE From Week 48 to Week 96
An AE was defined as 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. The percentage of participants who discontinued study intervention due to an AE from Week 48 up to Week 96 is reported for Group 1 participants and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.
Measured: Weeks 48-96 (up to ~48 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2020
- Study start18 Feb 2020
- Primary completion8 Sep 2021
- Study completion26 Aug 2024
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 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
- None (open label)
- Enrolment
- 672 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
- NCT04223778
- Sponsor's protocol ID
- 8591A-017
- Other IDs
- MK-8591A-017, 205165, 2019-000586-20, 2019
- Status last verified
- Feb 2026
- First submitted
- 8 Jan 2020
- Last updated
- 18 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Molina JM, Rizzardini G, Orrell C, Afani A, Calmy A, Oka S, Hinestrosa F, Kumar P, Tebas P, Walmsley S, Grandhi A, Klopfer S, Gendrano I, Eves K, Correll TA, Fox MC, Kim J. Switch to fixed-dose doravirine (100 mg) with islatravir (0.75 mg) once daily in virologically suppressed adults with HIV-1 on antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial. Lancet HIV. 2024 Jun;11(6):e369-e379. doi: 10.1016/S2352-3018(24)00031-6. Epub 2024 May 8.
PubMed 38734015
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT04223778
- Acronym / sponsor ID
- 8591A-017
- Conditions
- HIV Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 672 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 18 Feb 2020 (actual)
- Primary completion
- 8 Sep 2021 (actual)
- Study completion
- 26 Aug 2024 (actual)
- First posted
- 10 Jan 2020 (actual)
- Results
- Posted 19 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Experimental | Drug: DOR/ISLParticipants who were previously treated with continuous baseline antiretroviral therapy (ART) will receive DOR/ISL, a fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) orally once daily for 96 weeks. |
| Group 2: Baseline Antiretroviral Therapy (ART) | Active comparator | Drug: DOR/ISL, Drug: ARTParticipants received continuous baseline ART for 48 weeks. Continuing participants delayed switch over from baseline ART to DOR/ISL, fixed dose combination of 100 mg DOR/0.75 mg ISL orally once daily, from Week 48 to Week 96, a total DOR/ISL treatment duration of 48 Weeks. |
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 (HIV-1) positive
- Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen.
- Females are eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP); is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle; 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; if a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
Key exclusion criteria (9 listed)
- 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 Hepatitis B Virus (HBV) co-infection
- 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
- Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
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-8591AA FDC of 100 mg DOR/ 0.75 mg ISL taken in tablet form, orally, once daily | Drug | Group 1: Doravirine/Islatravir (DOR/ISL), Group 2: Baseline Antiretroviral Therapy (ART) |
| ARTBaseline ART regimen will be administered as per approved label. ART medication will not be provided by the Sponsor; participants will provide their own ART medications. Allowed drug classes include nucleoside analog reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transferase inhibitors (InSTIs), fusion inhibitors, chemokine receptor 5 (CCR5) antagonists, post-attachment inhibitor, and pharmacokinetic (PK) boosters. | Drug | Group 2: Baseline Antiretroviral Therapy (ART) |
Primary outcome
Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 Copies/mL at Week 48
Time frame: Week 48
HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime 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 is presented using the FDA Snapshot missing data approach.
Percentage of Participants With One or More Adverse Events (AEs) up to Week 48
Time frame: Up to ~48 Weeks
An AE was defined as 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. The percentage of participants who experienced at least one AE was reported.
Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48
Time frame: Up to ~48 Weeks
An AE was defined as 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. The percentage of participants who discontinued study intervention due to an AE was reported.
19 secondary outcomes
Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48
Time frame: Week 48
Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96
Time frame: Week 96
Group 1: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96
Time frame: Week 96
Percentage Change From Baseline in CD4+ T-cell Count at Week 48
Time frame: Baseline and Week 48
Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96
Time frame: Baseline and Week 96
Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96
Time frame: Week 48 and Week 96
Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48
Time frame: Week 48
Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96
Time frame: Week 96
Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)
Time frame: Baseline and Week 24
Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)
Time frame: Baseline and Week 24
Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens
Time frame: Baseline and Week 24
Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)
Time frame: Baseline and Week 48
Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)
Time frame: Baseline and Week 48
Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens
Time frame: Baseline and Week 48
Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens)
Time frame: Baseline and Week 48
Group 1: Percentage of Participants With One or More AEs up to Week 96
Time frame: Up to ~96 Weeks
Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96
Time frame: Up to ~96 Weeks
Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96
Time frame: Weeks 48-96 (up to ~48 weeks)
Group 1 & Group 2 (Switch-Over): Percentage of Participants Who Discontinued Study Intervention Due to an AE From Week 48 to Week 96
Time frame: Weeks 48-96 (up to ~48 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 38734015Molina JM, Rizzardini G, Orrell C, Afani A, Calmy A, Oka S, Hinestrosa F, Kumar P, Tebas P, Walmsley S, Grandhi A, Klopfer S, Gendrano I, Eves K, Correll TA, Fox MC, Kim J. Switch to fixed-dose doravirine (100 mg) with islatravir (0.75 mg) once daily in virologically suppressed adults with HIV-1 on antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial. Lancet HIV. 2024 Jun;11(6):e369-e379. doi: 10.1016/S2352-3018(24)00031-6. Epub 2024 May 8.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Plain Language SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/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
78 sites in 15 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 ART in people with HIV Infection, run by Merck Sharp & Dohme LLC at 78 sites in 15 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 9 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 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 78 sites in United States, Russia, Canada, France, Spain and 10 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 19 Sep 2022). 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 NCT04223778, 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 18 Feb 2026.