HIV-1 InfectionPhase 3NCT04233216
Doravirine/Islatravir (DOR/ISL) in Heavily Treatment-Experienced (HTE) Participants for Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-019)
A Phase 3 study testing ISL, DOR and DOR/ISL in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC at 98 sites in 18 countries.
Trial summary
This is a 2-part, phase 3 clinical study evaluating the antiretroviral activity and safety/tolerability of islatravir (ISL), doravirine (DOR), and a fixed dose combination (FDC) of DOR/ISL (also known as MK-8591A) in heavily treatment-experienced (HTE) participants with human immunodeficiency virus type 1 (HIV-1)… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- ISL, DOR and DOR/ISL
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 98 sitesin 18 countries
- Study dates
- 18 Mar 2020to 1 Nov 2023
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Is HIV-1 positive.
- Has been receiving the same baseline ART for ≥3 months prior to signing the Informed Consent Form/Assent Form.
- Weighs ≥35 kg.
- Has at least triple-class resistance (must include nucleoside reverse transcriptase inhibitor [NRTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], and resistance to either protease inhibitor (PI) or integrase strand transfer inhibitor (InSTI), based on central laboratory-based resistance or proviral DNA resistance testing at the Screening Visit, or historical resistance testing within 12 months of screening.
- Has ≤2 fully active antiretroviral drugs remaining among all antiretroviral classes that can be effectively combined to form a viable regimen based on resistance, tolerability, safety, drug access, or acceptability to participant.
- If female, is not pregnant or breastfeeding, and is: 1) not a woman of childbearing potential (WOCBP); 2) a WOCBP and uses an acceptable method of contraception/is abstinent; or 3) a WOCBP and has a negative pregnancy test within 24 hours of the first dose of study medication.
Who cannot join
- Has HIV 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 hepatitis B virus (HBV) co-infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive) and is not currently being treated for HBV.
- Has a history or current evidence of any condition, therapy (including active TB co-infection), laboratory abnormality or other circumstance (including drug or alcohol abuse or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with study participation for the full study duration.
- Is taking or is anticipated to require any of the prohibited therapies from the Screening Visit and throughout the study treatment period.
- Is taking DOR as part of his/her current failing antiretroviral regimen.
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- Is taking efavirenz (EFV), etravirine, or nevirapine.
- Is currently participating in or has participated in an interventional clinical study with an investigational compound or device from the Screening Visit through the study treatment period.
- Is female and is expecting to conceive or donate eggs at any time during the study.
Trial locations and contacts
98 sites in 18 countries.
98 sites in 18 countries
United States19 sites
University of Maryland ( Site 4023)
Baltimore, Maryland, 21201
Saint Hope Foundation, Inc. ( Site 4034)
Bellaire, Texas, 77401
University of Alabama at Birmingham 1917 Research Clinic ( Site 4031)
Birmingham, Alabama, 35222
University of North Carolina at Chapel Hill ( Site 4026)
Chapel Hill, North Carolina, 27599
Howard Brown Health Center ( Site 4006)
Chicago, Illinois, 60613
Northstar Healthcare ( Site 4004)
Chicago, Illinois, 60657
North Texas Infectious Diseases Consultants, PA ( Site 4005)
Dallas, Texas, 75246
The University of Mississippi Medical Center ( Site 4036)
Jackson, Mississippi, 39216
Men's Health Foundation ( Site 4018)
Los Angeles, California, 90069
The Kinder Medical Group ( Site 4014)
Miami, Florida, 33133
Yale School of Medicine ( Site 4007)
New Haven, Connecticut, 06510
Icahn School of Medicine at Mount Sinai ( Site 4000)
New York, New York, 10029
Saint Michael's Medical Center-Research - Infectious Disease ( Site 4035)
Newark, New Jersey, 07102
Orlando Immunology Center ( Site 4012)
Orlando, Florida, 32803
Palmtree Clinical Research, Inc. ( Site 4016)
Palm Springs, California, 92262
Chatham County Health Department ( Site 4029)
Savannah, Georgia, 31410
Dr. Peter Shalit, MD ( Site 4002)
Seattle, Washington, 98104
Georgetown University Hospital ( Site 4015)
Washington D.C., District of Columbia, 20007
Triple O Research Institute, P.A. ( Site 4020)
West Palm Beach, Florida, 33407
France11 sites
Hopital Avicenne ( Site 4702)
Bobigny, Seine-Saint-Denis, 93000
CHU de Bordeaux- Hopital Saint Andre ( Site 4715)
Bordeaux, Gironde, 33075
Hopital Edouard Herriot ( Site 4726)
Lyon, Ain, 69003
Hopital Europeen Marseille ( Site 4717)
Marseille, Bouches-du-Rhone, 13003
CHU de Montpellier - Hopital Saint-Eloi ( Site 4721)
Montpellier, Herault, 34295
CHU de Nice Hopital Archet 1 ( Site 4703)
Nice, Alpes-Maritimes, 06202
A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 4724)
Paris, Ain, 75018
Hopital Hotel Dieu [Paris, France] ( Site 4723)
Paris, 75004
A.P.H. Paris, Hopital Saint Louis ( Site 4714)
Paris, 75010
CHU de Rouen ( Site 4705)
Rouen, Haute-Normandie, 76031
Centre Hospitalier de Tourcoing ( Site 4700)
Tourcoing, Nord, 59208
Italy9 sites
Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 5001)
Milan, 20122
Universita' Vita Salute. Ospedale San Raffaele ( Site 5002)
Milan, 20127
Azienda Ospedaliera San Paolo ( Site 5003)
Milan, 20142
ASST Fatebenefratelli-Ospedale Sacco ( Site 5000)
Milan, 20157
Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 5004)
Modena, Emilia-Romagna, 41124
Ospedale San Gerardo ASST Monza ( Site 5012)
Monza, Monza E Brianza, 20900
IRCCS Policlinico San Matteo ( Site 5010)
Pavia, 27100
Istituto Nazionale per Le Malattie Infettive Lazzaro Spallanzani ( Site 5005)
Roma, 00149
Policlinico Gemelli Instituto di Clinica Chirurgica ( Site 5006)
Roma, 00168
Ukraine8 sites
MI Vinnytsia Regional Center of AIDS Prevention and Care ( Site 5618)
Berezina, Vinnytsia Oblast, 23222
Dnipropetrovsk Regional Center of Socially Significant Diseases ( Site 5619)
Dnipro, Dnipropetrovsk Oblast, 49115
Regional Clinical Infectious Hospital ( Site 5614)
Kharkiv, Kharkiv Oblast, 61096
Kherson City Clinical Hospital n.a. Y.Y. Karabelesh ( Site 5620)
Kherson, Kherson Oblast, 73000
Institute of Epidemiology and Infect Diseases of the NAMS of Ukraine ( Site 5615)
Kyiv, Kyivska Oblast, 03038
Kyiv City Clinical Hospital 5 ( Site 5616)
Kyiv, 03115
Mykolaiv center of paliative assistance and integrated services ( Site 5621)
Mykolayiv, Mykolaiv Oblast, 54003
MNE Odesa Regional Center of Socially Significant Diseases ( Site 5611)
Odesa, Odesa Oblast, 65014
Russia7 sites
Republican Clinical Hospital of Infectious Diseases n. a. A.F.Agafonov ( Site 5104)
Kazan', Tatarstan, Respublika, 420140
Infectious Clinical Hospital #2 ( Site 5114)
Moscow, Moscow, 105275
Saint Petersburg Center for Prophylactic of AIDS and Inf. Diseases ( Site 5101)
Saint Petersburg, Leningradskaya Oblast'
FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 5100)
Saint Petersburg, Sankt-Peterburg, 196645
Gbuz Samarskiy Oblastnoy Klinicheskiy Tsentr Profilaktiki I Bor'by So Spid ( Site 5113)
Samara, Samara Oblast, 443124
Smolensk Center On Aids And Infectious Diseases Prophylaxis ( Site 5115)
Smolensk, Smolensk Oblast, 214006
Regional Center for Prevent. and Control of AIDS and Inf. Diseases ( Site 5106)
Yekaterinburg, Sverdlovsk Oblast, 620102
Germany6 sites
ZIBP-Zentrum fur Infektiologie Berlin Prenzlauer Berg GmbH ( Site 4603)
Berlin, 10439
EPIMED GmbH ( Site 4608)
Berlin, 10787
Universitaetsklinikum Bonn ( Site 4600)
Bonn, North Rhine-Westphalia, 53127
Universitaetsklinikum Essen ( Site 4607)
Essen, North Rhine-Westphalia, 45122
ICH Study Center GmbH & Co.KG ( Site 4609)
Hamburg, 20146
Medizinische Hochschule Hannover ( Site 4612)
Hanover, Lower Saxony, 30625
Australia5 sites
Holdsworth House Medical Practice - Brisbane ( Site 5312)
Brisbane, Queensland, 4006
Monash Health-Monash Medical Centre ( Site 5313)
Clayton, Victoria, 3168
The Alfred Hospital ( Site 5304)
Melbourne, Victoria, 3004
Holdsworth House Medical Practice ( Site 5300)
Sydney, New South Wales, 2000
St Vincent's Hospital ( Site 5309)
Sydney, New South Wales, 2010
Canada5 sites
Hamilton Health Sciences ( Site 4115)
Hamilton, Ontario, L8L 2X2
McGill University Health Center - Research Institute-CVIS Clinical Research Unit ( Site 4102)
Montreal, Quebec, H4A 3J1
Ottawa Hospital Research Institute ( Site 4111)
Ottawa, Ontario, K1H 8L6
Toronto General Hospital - University Health Network ( Site 4105)
Toronto, Ontario, M5G 2N2
Vancouver ID Research and Care Centre Society ( Site 4100)
Vancouver, British Columbia, V6Z 2C7
Portugal5 sites
Hospital Dr. Fernando Fonseca, EPE - Amadora/Sintra ( Site 4902)
Amadora, Lisbon District, 2720-276
Hospital de Nossa Senhora da Oliveira- EPE ( Site 4905)
Guimarães, Braga District, 4835-044
Centro Hospitalar de Lisboa Norte Hospital de Santa Maria ( Site 4913)
Lisbon, 1649-035
Hospital Geral de Santo Antonio ( Site 4908)
Porto, 4099-001
Centro Hospitalar de Sao Joao. EPE - Hospital de Sao Joao ( Site 4907)
Porto, 4200-319
South Africa4 sites
FARMOVS ( Site 4805)
Bloemfontein, Free State, 9301
King Edward Hospital ( Site 4802)
Durban, KwaZulu-Natal, 4013
Wits Clinical HIV Research Unit ( Site 4804)
Johannesburg, Gauteng, 2041
Ezintsha ( Site 4806)
Johannesburg, Gauteng, 2193
Spain4 sites
Hospital Universitari Germans Trias i Pujol ( Site 5600)
Badalona, Barcelona, 08916
Hospital Clinic i Provincial ( Site 5601)
Barcelona, Catalonia, 08036
Hospital Santa Lucia ( Site 5603)
Cartagena, Murcia, Region de, 30202
Hospital Universitario La Paz ( Site 5604)
Madrid, 28046
Chile3 sites
Fundacion Arriaran ( Site 4401)
Santiago, Region M. de Santiago, 8360159
Centro Cardiovascular Cardiosur ( Site 4407)
Santiago, Region M. de Santiago, 8910259
Hospital Dr. Hernan Henriquez Aravena ( Site 4405)
Temuco, Araucania, 4781151
Peru3 sites
INMENSA ( Site 4506)
Lima, Muni Metro de Lima, 15046
Via Libre ( Site 4500)
Lima, 15001
Policlinico Universidad Nacional Mayor de San Marcos ( Site 4501)
Lima, 15081
South Korea3 sites
Pusan National University Hospital ( Site 5503)
Busan, Pusan-Kwangyokshi, 49241
Severance Hospital Yonsei University Health System ( Site 5500)
Seoul, 03722
The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 5502)
Seoul, 06591
Colombia2 sites
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 4306)
Bogotá, Bogota D.C., 111321
Fundacion Valle del Lili ( Site 4301)
Cali, Valle del Cauca Department, 760032
United Kingdom2 sites
Western General Hospital ( Site 5201)
Edinburgh, Edinburgh, City of, EH4 2XU
Royal Free Hospital ( Site 5202)
London, Camden, NW3 2QG
Japan1 site
Center Hospital of the National Center for Global Health and Medicine ( Site 5401)
Tokyo, 162-8655
About this study
Official title: A Phase 3, Randomized, Clinical Study in HIV-1-Infected Heavily Treatment-Experienced Participants Evaluating the Antiretroviral Activity of Blinded Islatravir (ISL), Doravirine (DOR), and Doravirine/Islatravir (DOR/ISL), Each Compared to Placebo, and the Antiretroviral Activity, Safety, and Tolerability of Open-Label DOR/ISL
This is a 2-part, phase 3 clinical study evaluating the antiretroviral activity and safety/tolerability of islatravir (ISL), doravirine (DOR), and a fixed dose combination (FDC) of DOR/ISL (also known as MK-8591A) in heavily treatment-experienced (HTE) participants with human immunodeficiency virus type 1 (HIV-1) infection. It is hypothesized that the percentage of participants receiving DOR/ISL to achieve ≥0.5 log10 decrease in HIV-1 ribonucleic acid (RNA) from study baseline (Day 1) to Day 8 is superior to placebo, each given in combination with failing antiretroviral therapy (ART).
Read the detailed description
Part 1 of this study (Day 1 to Day 7) is the double-blind period in which participants receive either ISL, DOR, DOR/ISL, or placebo. Part 2 of this study (Day 8 to Week 97) is the open-label period in which all participants receive DOR/ISL + optimized background therapy (OBT).
- Conditions
- HIV-1 Infection
- Being tested
- ISL, DOR, DOR/ISL, Placebo to ISL, Placebo to DOR
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISLDrug
Also called Islatravir, MK-8591
ISL 0.75 mg capsule taken by mouth.
DORDrug
Also called Doravirine, MK-1439
DOR 100 mg tablet taken by mouth.
DOR/ISLDrug
Also called Doravirine/Islatravir, MK-8591A
100 mg DOR/0.75 mg ISL FDC taken by mouth.
Placebo to ISLDrug
Placebo capsule matched to ISL taken by mouth.
Placebo to DORDrug
Placebo tablet matched to DOR taken by mouth.
| Study group | Role | What they receive |
|---|---|---|
| ISL + ART | Experimental | HTE participants with HIV-1 infection take ISL 0.75 mg once daily (QD) in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL fixed dose combination (FDC) QD + OBT from Day 8 to Week 97. Receives: Drug: ISL; Drug: DOR/ISL |
| DOR + ART | Experimental | HTE participants with HIV-1 infection take DOR 100 mg QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97. Receives: Drug: DOR; Drug: DOR/ISL |
| DOR/ISL + ART | Experimental | HTE participants with HIV-1 infection take 100 mg DOR/0.75 mg ISL FDC QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97. Receives: Drug: DOR/ISL |
| Placebo + ART | Placebo comparator | HTE participants with HIV-1 infection take placebo QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97. Receives: Drug: DOR/ISL; Drug: Placebo to ISL; Drug: Placebo to DOR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Receiving Doravirine/Islatravir (DOR/ISL) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Compared to Placebo Treatment
Participants with a ≥0.5 log10 decrease from Day 1 baseline to Day 8 in HIV-1 RNA were identified by the central laboratory with an Abbott Real Time Polymerase Chain Reaction (PCR) assay which has a lower limit of detection (LLOD) of 40 copies/mL Only participants treated with DOR/ISL FDC or placebo were analyzed in this outcome measure.
Measured: Day 1 (baseline) and Day 8
Percentage of Participants With ≥1 AEs Through Week 49
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to 49 weeks
Percentage of Participants Withdrawing From Study Treatment Due to AE(s) Through Week 25
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to 25 weeks
Percentage of Participants With ≥1 Adverse Events (AEs) Through Week 25
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to 25 weeks
Percentage of Participants Withdrawing From Study Treatment Due to AE(s) Through Week 49
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to 49 weeks
Secondary outcomes (56)
Percentage of Participants With ≥1 Adverse Events (AEs) Through Week 97
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measured: Up to 97 weeks
Percentage of Participants Discontinuing From Study Therapy Due to AE(s) Through Week 97
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measured: Up to 97 weeks
Percentage of Participants Receiving DOR or ISL (Given With Antiretroviral Therapy [ART]) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 HIV-1 RNA Compared to Placebo Treatment
Participants with a ≥0.5 log10 decrease from Day 1 baseline to Day 8 in HIV-1 RNA were identified by the central laboratory with an Abbott Real Time PCR assay which has a LLOD of 40 copies/mL Only participants treated with either DOR or ISL or placebo (given with ART) were analyzed in this outcome measure. Participants treated with DOR/ISL FDC were not analyzed in this outcome measure.
Measured: Day 1 (baseline) and Day 8
Mean Change From Baseline Day 1 to Day 8 in HIV-1 RNA Following Treatment With DOR/ISL (Given With ART), DOR, or ISL Compared to Placebo Treatment
The change from baseline Day to Day 8 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% confidence intervals (CIs) were calculated based on the t-distribution.
Measured: Day 1 (baseline) and Day 8
Percentage of Participants Receiving DOR/ISL (Given With ART), DOR, or ISL With ≥1.0 log10 Change From Day 1 Baseline to Day 8 HIV-1 RNA Compared to Placebo Treatment
Participants with a ≥1.0 log10 decrease from baseline (Day 1) to Day 8 in HIV-1 RNA were identified by at the central laboratory with an Abbott Real Time Polymerase Chain Reaction (PCR) assay which has a LLOD of 40 copies/mL
Measured: Day 1 (baseline) and Day 8
Percentage of Participants Receiving DOR/ISL (Given With ART) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 in HIV-1 RNA Compared to DOR or ISL Treatment
Participants with a ≥0.5 log10 decrease from baseline (Day 1) to Day 8 in HIV-1 RNA were identified by at the central laboratory with an Abbott Real Time PCR assay which has a lower limit of detection (LLOD) of 40 copies/mL Only participants treated with DOR/ISL or DOR alone or ISL alone were analyzed in this outcome measure. Participants treated with placebo were not analyzed in this outcome measure.
Measured: Day 1 (baseline) and Day 8
Mean Change From Baseline Day 1 to Day 8 in HIV-1 RNA Following Treatment With DOR/ISL (Given With ART) Compared to DOR or ISL Treatment
The change from baseline Day 1 to Day 8in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the t-distribution. The group treated with placebo were not analyzed in this outcome measure.
Measured: Day 1 (baseline) and Day 8
Percentage of Participants Receiving DOR/ISL (Given With ART) With ≥1.0 log10 Change From Day 1 Baseline to Day 8 in HIV-1 RNA Compared to DOR or ISL Treatment
Participants receiving DOR/ISL with a ≥1.0 log10 decrease from baseline (Day 1) to Day 8 in HIV-1 RNA were identified by at the central laboratory with an Abbott Real Time PCR assay which has a lower limit of detection (LLOD) of 40 copies/mL Only participants treated with DOR/ISL or DOR alone or ISL alone were analyzed in this outcome measure. Participants treated with placebo were not analyzed in this outcome measure.
Measured: Day 1 (baseline) and Day 8
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 1 Baseline to Week 25 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥0.5 log10 change from baseline Day 1 to Week 25 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 25
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 1 Baseline to Week 49 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥0.5 log10 change from baseline Day 1 to Week 49 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 49
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 1 Baseline to Week 97 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥0.5 log10 change from baseline Day 1 to Week 97 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 97
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 8 Baseline to Week 25 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥0.5 log10 change from baseline Day 8 to Week 25 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 25
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 8 Baseline to Week 49 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥0.5 log10 change from baseline Day 8 to Week 49 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 49
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 8 Baseline to Week 97 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥0.5 log10 change from baseline Day 8 to Week 97 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 97
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 1 Baseline to Week 25 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥1.0 log10 change from baseline Day 1 to Week 25 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 25
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 1 Baseline to Week 49 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥1.0 log10 change from baseline Day 1 to Week 49 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 49
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 1 Baseline to Week 97 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥1.0 log10 change from baseline Day 1 to Week 97 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 97
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 8 Baseline to Week 25 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥1.0 log10 change from baseline Day 8 to Week 25 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 25
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 8 Baseline to Week 49 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥1.0 log10 change from baseline Day 8 to Week 49 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 49
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 8 Baseline to Week 97 in HIV-1 RNA
The percentage of participants in the pooled treatment group with ≥1.0 log10 change from baseline Day 8 to Week 97 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 97
Mean Change From Baseline Day 1 to Week 25 in HIV-1 RNA From the Pooled Treatment Group
The change from baseline Day 1 to Week 25 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% confidence intervals (CIs) were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 25
Mean Change From Baseline Day 1 to Week 49 in HIV-1 RNA From the Pooled Treatment Group
The change from baseline Day 1 to Week 49 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% confidence intervals (CIs) were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 49
Mean Change From Baseline Day 1 to Week 97 in HIV-1 RNA From the Pooled Treatment Group
The change from baseline Day 1 to Week 97 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% confidence intervals (CIs) were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 97
Mean Change From Baseline Day 8 to Week 25 in HIV-1 RNA From the Pooled Treatment Group
The change from baseline Day 8 to Week 25 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% confidence intervals (CIs) were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 25
Mean Change From Baseline Day 8 to Week 49 in HIV-1 RNA From the Pooled Treatment Group
The change from baseline Day 8 to Week 49 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% confidence intervals (CIs) were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 49
Mean Change From Baseline Day 8 to Week 97 in HIV-1 RNA From the Pooled Treatment Group
The change from baseline Day 8 to Week 97 in HIV-1 RNA was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% confidence intervals (CIs) were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 97
Percentage of Participants From Day 1 Baseline to Day 8 With HIV-1 RNA <200 Copies mL
The percentage of participants with HIV-1 RNA <200 copies mL was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method.
Measured: Day 1 (baseline) and Day 8
Percentage of Participants From Day 1 Baseline to Day 8 With HIV-1 RNA <50 Copies mL
The percentage of participants with HIV-1 RNA <50 copies mL was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method.
Measured: Day 1 (baseline) and Day 8
Percentage of Participants From Day 1 Baseline to Day 8 With HIV-1 RNA <40 Copies mL
The percentage of participants with HIV-1 RNA <40 copies mL was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method.
Measured: Day 1 (baseline) and Day 8
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <200 Copies/mL at Week 25
The percentage of participants with HIV-1 RNA <200 copies mL at week 25 was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method. Analysis of the pooled treatment group was planned per protocol,
Measured: Week 25
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <200 Copies/mL at Week 49
The percentage of participants with HIV-1 RNA <200 copies mL at week 49 was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method. Analysis of the pooled treatment group was planned per protocol,
Measured: Week 49
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <200 Copies/mL at Week 97
The percentage of participants with HIV-1 RNA <200 copies mL at week 97 was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method. Analysis of the pooled treatment group was planned per protocol,
Measured: Week 97
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <50 Copies/mL at Week 25
The percentage of participants with HIV-1 RNA <50 copies mL at week 25 was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method. Analysis of the pooled treatment group was planned per protocol,
Measured: Week 25
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <50 Copies/mL at Week 49
The percentage of participants with HIV-1 RNA <50 copies mL at week 49 was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method. Analysis of the pooled treatment group was planned per protocol,
Measured: Week 49
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <50 Copies/mL at Week 97
The percentage of participants with HIV-1 RNA <50 copies mL at week 97 was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method. Analysis of the pooled treatment group was planned per protocol,
Measured: Week 97
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <40 Copies/mL at Week 25
The percentage of participants with HIV-1 RNA <40 copies mL at week 25 was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method. Analysis of the pooled treatment group was planned per protocol,
Measured: Week 25
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <40 Copies/mL at Week 49
The percentage of participants with HIV-1 RNA <40 copies mL at week 49 was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method. Analysis of the pooled treatment group was planned per protocol.
Measured: Week 49
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <40 Copies/mL at Week 97
The percentage of participants with HIV-1 RNA <40 copies mL at week 97 was determined by the central laboratory using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The within-group 95% CIs were calculated based on the Clopper-Pearson method. Analysis of the pooled treatment group was planned per protocol,
Measured: Week 97
Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to DOR at Week 25
The prevalence of viral drug resistance to DOR was based on the percentage of participants with treatment-emergent (TE) resistance-associated substitutions (RASs), which is calculated by dividing the number of participants with TE RASs by the number of participants tested for resistance multiplied by 100. RASs for DOR were as follows: V106A/M, Y188C/L, F227C/H/I/L, M230I/L, L234I, Y318F, V108I, Y188F/H, G190E, H221Y, P236, and were determined by the central laboratory with the GenoSure Prime assay on post randomization samples from participants with HIV-1 RNA ≥200 copies/mL Analysis of the pooled treatment group was planned per protocol.
Measured: Week 25
Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to DOR at Week 49
The prevalence of viral drug resistance to DOR was based on the percentage of participants with TE RASs, which is calculated by dividing the number of participants with TE RASs by the number of participants tested for resistance, multiplied by 100. RASs for DOR were as follows: V106A/M, Y188C/L, F227C/H/I/L, M230I/L, L234I, Y318F, V108I, Y188F/H, G190E, H221Y, P236, and were determined by the central laboratory with the GenoSure Prime assay on post randomization samples from participants with HIV-1 RNA ≥200 copies/mL Analysis of the pooled treatment group was planned per protocol.
Measured: Week 49
Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to ISL at Week 25
The prevalence of viral drug resistance to ISL was based on the percentage of participants with TE RAS, which is calculated by dividing the number of participants with TE RAS by the number of participants tested for resistance, multiplied by 100. The RAS for ISL, M184V was determined by the central laboratory with the GenoSure Prime assay on post randomization samples from participants with HIV-1 RNA ≥200 copies/mL Analysis of the pooled treatment group was planned per protocol.
Measured: Week 25
Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to ISL at Week 49
The prevalence of viral drug resistance to ISL was based on the percentage of participants with TE RAS, which is calculated by dividing the number of participants with TE RAS by the number of participants tested for resistance, multiplied by 100. The RAS for ISL, M184V was determined by the central laboratory with the GenoSure Prime assay on post randomization samples from participants with HIV-1 RNA ≥200 copies/mL Analysis of the pooled treatment group was planned per protocol.
Measured: Week 49
Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to Optimized Background Therapy (OBT) Components at Week 25
The prevalence of viral drug resistance to OBT components was based on the percentage of participants with TE RASs, which is calculated by dividing the number of participants with TE RASs by the number of participants tested for resistance, multiplied by 100. The RASs for OBT components were determined by the central laboratory with the GenoSure Prime assay on post randomization samples from participants with HIV-1 RNA ≥200 copies/mL Analysis of the pooled treatment group was planned per protocol.
Measured: Week 25
Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to OBT Components at Week 49
The prevalence of viral drug resistance to OBT components was based on the percentage of participants with TE RASs, which is calculated by dividing the number of participants with TE RASs by the number of participants tested for resistance, multiplied by 100. The RASs for OBT components were determined by the central laboratory with the GenoSure Prime assay on post randomization samples from participants with HIV-1 RNA ≥200 copies/mL Analysis of the pooled treatment group was planned per protocol.
Measured: Week 49
Number of Participants From the Pooled Treatment Group With Viral Resistance-associated Substitutions (RASs) at Week 25
The number of participants from the pooled treatment group who had HIV-1 RNA ≥200 copies/mL with treatment emergent RAS at week 25 showing the type of RAS .Analysis of the pooled treatment group was planned per protocol,
Measured: Week 25
Number of Participants From the Pooled Treatment Group With Viral RASs at Week 49
The number of participants from the pooled treatment group who had HIV-1 RNA ≥200 copies/mL with treatment emergent RAS at week 49 showing the type of RAS .Analysis of the pooled treatment group was planned per protocol,
Measured: Week 49
Number of Participants From the Pooled Treatment Group With Viral RASs at Week 97
The number of participants from the pooled treatment group with treatment emergent RAS at week 97 are presented, showing the type of RAS .Analysis of the pooled treatment group was planned per protocol,
Measured: Week 97
Number of Participants From the Pooled Treatment Group Exhibiting Antiviral Resistance of HIV-1 RNA ≥200 Copies/mL at Week 25
The number of participants from the pooled treatment group exhibiting antiviral resistance of HIV-1 RNA ≥200 copies/mL at Week 25 is presented. .Analysis of the pooled treatment group was planned per protocol,
Measured: Week 25
Number of Participants From the Pooled Treatment Group Exhibiting Antiviral Resistance of HIV-1 RNA ≥200 Copies/mL at Week 49
The number of participants from the pooled treatment group exhibiting antiviral resistance of HIV-1 RNA ≥200 copies/mL at Week 49 is presented. .Analysis of the pooled treatment group was planned per protocol,
Measured: Week 49
Number of Participants From the Pooled Treatment Group Exhibiting Antiviral Resistance of HIV-1 RNA ≥200 Copies/mL at Week 97
The number of participants from the pooled treatment group exhibiting antiviral resistance of HIV-1 RNA ≥200 copies/mL at Week 97 is presented. .Analysis of the pooled treatment group was planned per protocol,
Measured: Week 97
Change From Baseline Day 1 to Week 25 in Cluster of Differentiation 4+ (CD4+) T-cell Counts From the Pooled Treatment Group
The change from baseline Day 1 to Week 25 in CD4+ T-cell counts was determined by the central laboratory.. The within-group 95% CIs were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 25
Change From Baseline Day 1 to Week 49 in CD4+ T-cell Counts From the Pooled Treatment Group
The change from baseline Day 1 to Week 49 in CD4+ T-cell counts was determined by the central laboratory.. The within-group 95% CIs were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 49
Change From Baseline Day 1 to Week 97 in CD4+ T-cell Counts From the Pooled Treatment Group
The change from baseline Day 1 to Week 97 in CD4+ T-cell counts was determined by the central laboratory.. The within-group 95% CIs were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 1 (baseline) and Week 97
Change From Baseline Day 8 to Week 25 in CD4+ T-cell Counts From the Pooled Treatment Group
The change from baseline Day 8 to Week 25 in CD4+ T-cell counts was determined by the central laboratory.. The within-group 95% CIs were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 25
Change From Baseline Day 8 to Week 49 in CD4+ T-cell Counts From the Pooled Treatment Group
The change from baseline Day 8 to Week 49 in CD4+ T-cell counts was determined by the central laboratory.. The within-group 95% CIs were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 49
Change From Baseline Day 8 to Week 97 in CD4+ T-cell Counts From the Pooled Treatment Group
The change from baseline Day 8 to Week 97 in CD4+ T-cell counts was determined by the central laboratory.. The within-group 95% CIs were calculated based on the t-distribution. Analysis of the pooled treatment group was planned per protocol,
Measured: Day 8 (baseline) and Week 97
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 start18 Mar 2020
- Primary completion21 Nov 2022
- Study completion1 Nov 2023
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
- 35 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
- NCT04233216
- Sponsor's protocol ID
- 8591A-019
- Other IDs
- MK-8591A-019, 205243, 2019-000588-26, 2019
- Status last verified
- Dec 2024
- First submitted
- 15 Jan 2020
- Last updated
- 27 Dec 2024
- 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
Carr A, Mngqibisa R, Khaertynova I, Kumar PN, Haider S, Zhang Y, Correll T, Asante-Appiah E, Greaves W. Efficacy and safety of doravirine/islatravir in heavily treatment-experienced participants living with HIV-1: results from a randomized trial. AIDS. 2026 Feb 1;40(2):189-197. doi: 10.1097/QAD.0000000000004367. Epub 2025 Oct 1.
PubMed 41037024
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Clinical Study in HIV-1-Infected Heavily Treatment-Experienced Participants Evaluating the Antiretroviral Activity of Blinded Islatravir (ISL), Doravirine (DOR), and Doravirine/Islatravir (DOR/ISL), Each Compared to Placebo, and the Antiretroviral Activity, Safety, and Tolerability of Open-Label DOR/ISL
- ClinicalTrials.gov ID
- NCT04233216
- Acronym / sponsor ID
- 8591A-019
- Conditions
- HIV-1 Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 18 Mar 2020 (actual)
- Primary completion
- 21 Nov 2022 (actual)
- Study completion
- 1 Nov 2023 (actual)
- First posted
- 18 Jan 2020 (actual)
- Results
- Posted 8 Dec 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 2-part, phase 3 clinical study evaluating the antiretroviral activity and safety/tolerability of islatravir (ISL), doravirine (DOR), and a fixed dose combination (FDC) of DOR/ISL (also known as MK-8591A) in heavily treatment-experienced (HTE) participants with human immunodeficiency virus type 1 (HIV-1) infection. It is hypothesized that the percentage of participants receiving DOR/ISL to achieve ≥0.5 log10 decrease in HIV-1 ribonucleic acid (RNA) from study baseline (Day 1) to Day 8 is superior to placebo, each given in combination with failing antiretroviral therapy (ART).
Detailed description
Part 1 of this study (Day 1 to Day 7) is the double-blind period in which participants receive either ISL, DOR, DOR/ISL, or placebo. Part 2 of this study (Day 8 to Week 97) is the open-label period in which all participants receive DOR/ISL + optimized background therapy (OBT).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ISL + ART | Experimental | Drug: ISL, Drug: DOR/ISLHTE participants with HIV-1 infection take ISL 0.75 mg once daily (QD) in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL fixed dose combination (FDC) QD + OBT from Day 8 to Week 97. |
| DOR + ART | Experimental | Drug: DOR, Drug: DOR/ISLHTE participants with HIV-1 infection take DOR 100 mg QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97. |
| DOR/ISL + ART | Experimental | Drug: DOR/ISLHTE participants with HIV-1 infection take 100 mg DOR/0.75 mg ISL FDC QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97. |
| Placebo + ART | Placebo comparator | Drug: DOR/ISL, Drug: Placebo to ISL, Drug: Placebo to DORHTE participants with HIV-1 infection take placebo QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Is HIV-1 positive.
- Has been receiving the same baseline ART for ≥3 months prior to signing the Informed Consent Form/Assent Form.
- Weighs ≥35 kg.
- Has at least triple-class resistance (must include nucleoside reverse transcriptase inhibitor [NRTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], and resistance to either protease inhibitor (PI) or integrase strand transfer inhibitor (InSTI), based on central laboratory-based resistance or proviral DNA resistance testing at the Screening Visit, or historical resistance testing within 12 months of screening.
- Has ≤2 fully active antiretroviral drugs remaining among all antiretroviral classes that can be effectively combined to form a viable regimen based on resistance, tolerability, safety, drug access, or acceptability to participant.
Key exclusion criteria (9 listed)
- Has HIV 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 hepatitis B virus (HBV) co-infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive) and is not currently being treated for HBV.
- Has a history or current evidence of any condition, therapy (including active TB co-infection), laboratory abnormality or other circumstance (including drug or alcohol abuse or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with study participation for the full study duration.
- Is taking or is anticipated to require any of the prohibited therapies from the Screening Visit and throughout the study treatment period.
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 |
|---|---|---|
| ISLAlso: Islatravir, MK-8591ISL 0.75 mg capsule taken by mouth. | Drug | ISL + ART |
| DORAlso: Doravirine, MK-1439DOR 100 mg tablet taken by mouth. | Drug | DOR + ART |
| DOR/ISLAlso: Doravirine/Islatravir, MK-8591A100 mg DOR/0.75 mg ISL FDC taken by mouth. | Drug | DOR + ART, DOR/ISL + ART, ISL + ART, Placebo + ART |
| Placebo to ISLPlacebo capsule matched to ISL taken by mouth. | Drug | Placebo + ART |
| Placebo to DORPlacebo tablet matched to DOR taken by mouth. | Drug | Placebo + ART |
Primary outcome
Percentage of Participants Receiving Doravirine/Islatravir (DOR/ISL) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Compared to Placebo Treatment
Time frame: Day 1 (baseline) and Day 8
Participants with a ≥0.5 log10 decrease from Day 1 baseline to Day 8 in HIV-1 RNA were identified by the central laboratory with an Abbott Real Time Polymerase Chain Reaction (PCR) assay which has a lower limit of detection (LLOD) of 40 copies/mL Only participants treated with DOR/ISL FDC or placebo were analyzed in this outcome measure.
Percentage of Participants With ≥1 AEs Through Week 49
Time frame: Up to 49 weeks
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Percentage of Participants Withdrawing From Study Treatment Due to AE(s) Through Week 25
Time frame: Up to 25 weeks
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Percentage of Participants With ≥1 Adverse Events (AEs) Through Week 25
Time frame: Up to 25 weeks
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Percentage of Participants Withdrawing From Study Treatment Due to AE(s) Through Week 49
Time frame: Up to 49 weeks
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
56 secondary outcomes
Percentage of Participants With ≥1 Adverse Events (AEs) Through Week 97
Time frame: Up to 97 weeks
Percentage of Participants Discontinuing From Study Therapy Due to AE(s) Through Week 97
Time frame: Up to 97 weeks
Percentage of Participants Receiving DOR or ISL (Given With Antiretroviral Therapy [ART]) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 HIV-1 RNA Compared to Placebo Treatment
Time frame: Day 1 (baseline) and Day 8
Mean Change From Baseline Day 1 to Day 8 in HIV-1 RNA Following Treatment With DOR/ISL (Given With ART), DOR, or ISL Compared to Placebo Treatment
Time frame: Day 1 (baseline) and Day 8
Percentage of Participants Receiving DOR/ISL (Given With ART), DOR, or ISL With ≥1.0 log10 Change From Day 1 Baseline to Day 8 HIV-1 RNA Compared to Placebo Treatment
Time frame: Day 1 (baseline) and Day 8
Percentage of Participants Receiving DOR/ISL (Given With ART) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 in HIV-1 RNA Compared to DOR or ISL Treatment
Time frame: Day 1 (baseline) and Day 8
Mean Change From Baseline Day 1 to Day 8 in HIV-1 RNA Following Treatment With DOR/ISL (Given With ART) Compared to DOR or ISL Treatment
Time frame: Day 1 (baseline) and Day 8
Percentage of Participants Receiving DOR/ISL (Given With ART) With ≥1.0 log10 Change From Day 1 Baseline to Day 8 in HIV-1 RNA Compared to DOR or ISL Treatment
Time frame: Day 1 (baseline) and Day 8
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 1 Baseline to Week 25 in HIV-1 RNA
Time frame: Day 1 (baseline) and Week 25
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 1 Baseline to Week 49 in HIV-1 RNA
Time frame: Day 1 (baseline) and Week 49
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 1 Baseline to Week 97 in HIV-1 RNA
Time frame: Day 1 (baseline) and Week 97
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 8 Baseline to Week 25 in HIV-1 RNA
Time frame: Day 8 (baseline) and Week 25
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 8 Baseline to Week 49 in HIV-1 RNA
Time frame: Day 8 (baseline) and Week 49
Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 8 Baseline to Week 97 in HIV-1 RNA
Time frame: Day 8 (baseline) and Week 97
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 1 Baseline to Week 25 in HIV-1 RNA
Time frame: Day 1 (baseline) and Week 25
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 1 Baseline to Week 49 in HIV-1 RNA
Time frame: Day 1 (baseline) and Week 49
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 1 Baseline to Week 97 in HIV-1 RNA
Time frame: Day 1 (baseline) and Week 97
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 8 Baseline to Week 25 in HIV-1 RNA
Time frame: Day 8 (baseline) and Week 25
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 8 Baseline to Week 49 in HIV-1 RNA
Time frame: Day 8 (baseline) and Week 49
Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 8 Baseline to Week 97 in HIV-1 RNA
Time frame: Day 8 (baseline) and Week 97
Mean Change From Baseline Day 1 to Week 25 in HIV-1 RNA From the Pooled Treatment Group
Time frame: Day 1 (baseline) and Week 25
Mean Change From Baseline Day 1 to Week 49 in HIV-1 RNA From the Pooled Treatment Group
Time frame: Day 1 (baseline) and Week 49
Mean Change From Baseline Day 1 to Week 97 in HIV-1 RNA From the Pooled Treatment Group
Time frame: Day 1 (baseline) and Week 97
Mean Change From Baseline Day 8 to Week 25 in HIV-1 RNA From the Pooled Treatment Group
Time frame: Day 8 (baseline) and Week 25
Mean Change From Baseline Day 8 to Week 49 in HIV-1 RNA From the Pooled Treatment Group
Time frame: Day 8 (baseline) and Week 49
Mean Change From Baseline Day 8 to Week 97 in HIV-1 RNA From the Pooled Treatment Group
Time frame: Day 8 (baseline) and Week 97
Percentage of Participants From Day 1 Baseline to Day 8 With HIV-1 RNA <200 Copies mL
Time frame: Day 1 (baseline) and Day 8
Percentage of Participants From Day 1 Baseline to Day 8 With HIV-1 RNA <50 Copies mL
Time frame: Day 1 (baseline) and Day 8
Percentage of Participants From Day 1 Baseline to Day 8 With HIV-1 RNA <40 Copies mL
Time frame: Day 1 (baseline) and Day 8
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <200 Copies/mL at Week 25
Time frame: Week 25
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <200 Copies/mL at Week 49
Time frame: Week 49
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <200 Copies/mL at Week 97
Time frame: Week 97
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <50 Copies/mL at Week 25
Time frame: Week 25
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <50 Copies/mL at Week 49
Time frame: Week 49
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <50 Copies/mL at Week 97
Time frame: Week 97
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <40 Copies/mL at Week 25
Time frame: Week 25
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <40 Copies/mL at Week 49
Time frame: Week 49
Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <40 Copies/mL at Week 97
Time frame: Week 97
Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to DOR at Week 25
Time frame: Week 25
Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to DOR at Week 49
Time frame: Week 49
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41037024Carr A, Mngqibisa R, Khaertynova I, Kumar PN, Haider S, Zhang Y, Correll T, Asante-Appiah E, Greaves W. Efficacy and safety of doravirine/islatravir in heavily treatment-experienced participants living with HIV-1: results from a randomized trial. AIDS. 2026 Feb 1;40(2):189-197. doi: 10.1097/QAD.0000000000004367. Epub 2025 Oct 1.
- Merck Clinical Trials InformationLink 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
98 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ISL, DOR and DOR/ISL in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC at 98 sites in 18 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 6 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 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 98 sites in United States, France, Italy, Ukraine, Russia and 13 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. Some participants in this study may receive a placebo. 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 8 Dec 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 Receiving Doravirine/Islatravir (DOR/ISL) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Compared to Placebo Treatment (time frame: Day 1 (baseline) and Day 8). The study lists 5 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 NCT04233216, 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 27 Dec 2024.