Doravirine/Islatravir (DOR/ISL) in Heavily Treatment-Experienced (HTE) Participants for Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-019)

NCT04233216 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 8591A-019MK-8591A-0192052432019-000588-26
• Study Type: interventional
• Target: 35
• Locations: 18 countries
• Sites: 98

Brief 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) 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).

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  Up to 49 weeks

Secondary Outcomes (56)

• Percentage of Participants With ≥1 Adverse Events (AEs) Through Week 97

  Up to 97 weeks

• Percentage of Participants Discontinuing From Study Therapy Due to AE(s) Through Week 97

  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

  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

  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

  Day 1 (baseline) and Day 8

Study Arms (4)

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.

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.

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.

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.

Drug: DOR/ISL; Drug: Placebo to ISL; Drug: Placebo to DOR

Interventions

ISL DRUG

ISL 0.75 mg capsule taken by mouth.

Also known as: Islatravir, MK-8591

ISL + ART

DOR DRUG

DOR 100 mg tablet taken by mouth.

Also known as: Doravirine, MK-1439

DOR + ART

DOR/ISL DRUG

100 mg DOR/0.75 mg ISL FDC taken by mouth.

Also known as: Doravirine/Islatravir, MK-8591A

DOR + ART; DOR/ISL + ART; ISL + ART; Placebo + ART

Placebo to ISL DRUG

Placebo capsule matched to ISL taken by mouth.

Placebo + ART

Placebo to DOR DRUG

Placebo tablet matched to DOR taken by mouth.

Placebo + ART

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (98)

University of Alabama at Birmingham 1917 Research Clinic ( Site 4031)

Birmingham, Alabama, 35222, United States

Location

Men's Health Foundation ( Site 4018)

Los Angeles, California, 90069, United States

Location

Palmtree Clinical Research, Inc. ( Site 4016)

Palm Springs, California, 92262, United States

Location

Yale School of Medicine ( Site 4007)

New Haven, Connecticut, 06510, United States

Location

Georgetown University Hospital ( Site 4015)

Washington D.C., District of Columbia, 20007, United States

Location

The Kinder Medical Group ( Site 4014)

Miami, Florida, 33133, United States

Location

Orlando Immunology Center ( Site 4012)

Orlando, Florida, 32803, United States

Location

Triple O Research Institute, P.A. ( Site 4020)

West Palm Beach, Florida, 33407, United States

Location

Chatham County Health Department ( Site 4029)

Savannah, Georgia, 31410, United States

Location

Howard Brown Health Center ( Site 4006)

Chicago, Illinois, 60613, United States

Location

Northstar Healthcare ( Site 4004)

Chicago, Illinois, 60657, United States

Location

University of Maryland ( Site 4023)

Baltimore, Maryland, 21201, United States

Location

The University of Mississippi Medical Center ( Site 4036)

Jackson, Mississippi, 39216, United States

Location

Saint Michael's Medical Center-Research - Infectious Disease ( Site 4035)

Newark, New Jersey, 07102, United States

Location

Icahn School of Medicine at Mount Sinai ( Site 4000)

New York, New York, 10029, United States

Location

University of North Carolina at Chapel Hill ( Site 4026)

Chapel Hill, North Carolina, 27599, United States

Location

Saint Hope Foundation, Inc. ( Site 4034)

Bellaire, Texas, 77401, United States

Location

North Texas Infectious Diseases Consultants, PA ( Site 4005)

Dallas, Texas, 75246, United States

Location

Dr. Peter Shalit, MD ( Site 4002)

Seattle, Washington, 98104, United States

Location

Holdsworth House Medical Practice ( Site 5300)

Sydney, New South Wales, 2000, Australia

Location

St Vincent's Hospital ( Site 5309)

Sydney, New South Wales, 2010, Australia

Location

Holdsworth House Medical Practice - Brisbane ( Site 5312)

Brisbane, Queensland, 4006, Australia

Location

Monash Health-Monash Medical Centre ( Site 5313)

Clayton, Victoria, 3168, Australia

Location

The Alfred Hospital ( Site 5304)

Melbourne, Victoria, 3004, Australia

Location

Vancouver ID Research and Care Centre Society ( Site 4100)

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Hamilton Health Sciences ( Site 4115)

Hamilton, Ontario, L8L 2X2, Canada

Location

Ottawa Hospital Research Institute ( Site 4111)

Ottawa, Ontario, K1H 8L6, Canada

Location

Toronto General Hospital - University Health Network ( Site 4105)

Toronto, Ontario, M5G 2N2, Canada

Location

McGill University Health Center - Research Institute-CVIS Clinical Research Unit ( Site 4102)

Montreal, Quebec, H4A 3J1, Canada

Location

Fundacion Arriaran ( Site 4401)

Santiago, Region M. de Santiago, 8360159, Chile

Location

Centro Cardiovascular Cardiosur ( Site 4407)

Santiago, Region M. de Santiago, 8910259, Chile

Location

Hospital Dr. Hernan Henriquez Aravena ( Site 4405)

Temuco, Región de la Araucanía, 4781151, Chile

Location

Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 4306)

Bogotá, Bogota D.C., 111321, Colombia

Location

Fundacion Valle del Lili ( Site 4301)

Cali, Valle del Cauca Department, 760032, Colombia

Location

Hopital Edouard Herriot ( Site 4726)

Lyon, Ain, 69003, France

Location

A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 4724)

Paris, Ain, 75018, France

Location

CHU de Nice Hopital Archet 1 ( Site 4703)

Nice, Alpes-Maritimes, 06202, France

Location

Hopital Europeen Marseille ( Site 4717)

Marseille, Bouches-du-Rhone, 13003, France

Location

CHU de Bordeaux- Hopital Saint Andre ( Site 4715)

Bordeaux, Gironde, 33075, France

Location

CHU de Rouen ( Site 4705)

Rouen, Haute-Normandie, 76031, France

Location

CHU de Montpellier - Hopital Saint-Eloi ( Site 4721)

Montpellier, Herault, 34295, France

Location

Centre Hospitalier de Tourcoing ( Site 4700)

Tourcoing, Nord, 59208, France

Location

Hopital Avicenne ( Site 4702)

Bobigny, Seine-Saint-Denis, 93000, France

Location

Hopital Hotel Dieu [Paris, France] ( Site 4723)

Paris, 75004, France

Location

A.P.H. Paris, Hopital Saint Louis ( Site 4714)

Paris, 75010, France

Location

Medizinische Hochschule Hannover ( Site 4612)

Hanover, Lower Saxony, 30625, Germany

Location

Universitaetsklinikum Bonn ( Site 4600)

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Universitaetsklinikum Essen ( Site 4607)

Essen, North Rhine-Westphalia, 45122, Germany

Location

ZIBP-Zentrum fur Infektiologie Berlin Prenzlauer Berg GmbH ( Site 4603)

Berlin, 10439, Germany

Location

EPIMED GmbH ( Site 4608)

Berlin, 10787, Germany

Location

ICH Study Center GmbH & Co.KG ( Site 4609)

Hamburg, 20146, Germany

Location

Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 5004)

Modena, Emilia-Romagna, 41124, Italy

Location

Ospedale San Gerardo ASST Monza ( Site 5012)

Monza, Monza E Brianza, 20900, Italy

Location

Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 5001)

Milan, 20122, Italy

Location

Universita' Vita Salute. Ospedale San Raffaele ( Site 5002)

Milan, 20127, Italy

Location

Azienda Ospedaliera San Paolo ( Site 5003)

Milan, 20142, Italy

Location

ASST Fatebenefratelli-Ospedale Sacco ( Site 5000)

Milan, 20157, Italy

Location

IRCCS Policlinico San Matteo ( Site 5010)

Pavia, 27100, Italy

Location

Istituto Nazionale per Le Malattie Infettive Lazzaro Spallanzani ( Site 5005)

Roma, 00149, Italy

Location

Policlinico Gemelli Instituto di Clinica Chirurgica ( Site 5006)

Roma, 00168, Italy

Location

Center Hospital of the National Center for Global Health and Medicine ( Site 5401)

Tokyo, 162-8655, Japan

Location

INMENSA ( Site 4506)

Lima, Muni Metro de Lima, 15046, Peru

Location

Via Libre ( Site 4500)

Lima, 15001, Peru

Location

Policlinico Universidad Nacional Mayor de San Marcos ( Site 4501)

Lima, 15081, Peru

Location

Hospital de Nossa Senhora da Oliveira- EPE ( Site 4905)

Guimarães, Braga District, 4835-044, Portugal

Location

Hospital Dr. Fernando Fonseca, EPE - Amadora/Sintra ( Site 4902)

Amadora, Lisbon District, 2720-276, Portugal

Location

Centro Hospitalar de Lisboa Norte Hospital de Santa Maria ( Site 4913)

Lisbon, 1649-035, Portugal

Location

Hospital Geral de Santo Antonio ( Site 4908)

Porto, 4099-001, Portugal

Location

Centro Hospitalar de Sao Joao. EPE - Hospital de Sao Joao ( Site 4907)

Porto, 4200-319, Portugal

Location

HOPE Clinical Research ( Site 5700)

San Juan, 00909, Puerto Rico

Location

Saint Petersburg Center for Prophylactic of AIDS and Inf. Diseases ( Site 5101)

Saint Petersburg, Leningradskaya Oblast', Russia

Location

Infectious Clinical Hospital #2 ( Site 5114)

Moscow, Moscow, 105275, Russia

Location

Gbuz Samarskiy Oblastnoy Klinicheskiy Tsentr Profilaktiki I Bor'by So Spid ( Site 5113)

Samara, Samara Oblast, 443124, Russia

Location

FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 5100)

Saint Petersburg, Sankt-Peterburg, 196645, Russia

Location

Smolensk Center On Aids And Infectious Diseases Prophylaxis ( Site 5115)

Smolensk, Smolensk Oblast, 214006, Russia

Location

Regional Center for Prevent. and Control of AIDS and Inf. Diseases ( Site 5106)

Yekaterinburg, Sverdlovsk Oblast, 620102, Russia

Location

Republican Clinical Hospital of Infectious Diseases n. a. A.F.Agafonov ( Site 5104)

Kazan', Tatarstan, Respublika, 420140, Russia

Location

FARMOVS ( Site 4805)

Bloemfontein, Free State, 9301, South Africa

Location

Wits Clinical HIV Research Unit ( Site 4804)

Johannesburg, Gauteng, 2041, South Africa

Location

Ezintsha ( Site 4806)

Johannesburg, Gauteng, 2193, South Africa

Location

King Edward Hospital ( Site 4802)

Durban, KwaZulu-Natal, 4013, South Africa

Location

Pusan National University Hospital ( Site 5503)

Busan, Pusan-Kwangyokshi, 49241, South Korea

Location

Severance Hospital Yonsei University Health System ( Site 5500)

Seoul, 03722, South Korea

Location

The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 5502)

Seoul, 06591, South Korea

Location

Hospital Universitari Germans Trias i Pujol ( Site 5600)

Badalona, Barcelona, 08916, Spain

Location

Hospital Clinic i Provincial ( Site 5601)

Barcelona, Catalonia, 08036, Spain

Location

Hospital Santa Lucia ( Site 5603)

Cartagena, Murcia, Region de, 30202, Spain

Location

Hospital Universitario La Paz ( Site 5604)

Madrid, 28046, Spain

Location

Dnipropetrovsk Regional Center of Socially Significant Diseases ( Site 5619)

Dnipro, Dnipropetrovsk Oblast, 49115, Ukraine

Location

Regional Clinical Infectious Hospital ( Site 5614)

Kharkiv, Kharkivs’ka Oblast’, 61096, Ukraine

Location

Kherson City Clinical Hospital n.a. Y.Y. Karabelesh ( Site 5620)

Kherson, Kherson Oblast, 73000, Ukraine

Location

Institute of Epidemiology and Infect Diseases of the NAMS of Ukraine ( Site 5615)

Kyiv, Kyivska Oblast, 03038, Ukraine

Location

Mykolaiv center of paliative assistance and integrated services ( Site 5621)

Mykolayiv, Mykolaiv Oblast, 54003, Ukraine

Location

MNE Odesa Regional Center of Socially Significant Diseases ( Site 5611)

Odesa, Odesa Oblast, 65014, Ukraine

Location

MI Vinnytsia Regional Center of AIDS Prevention and Care ( Site 5618)

Berezina, Vinnytsia Oblast, 23222, Ukraine

Location

Kyiv City Clinical Hospital 5 ( Site 5616)

Kyiv, 03115, Ukraine

Location

Royal Free Hospital ( Site 5202)

London, Camden, NW3 2QG, United Kingdom

Location

Western General Hospital ( Site 5201)

Edinburgh, Edinburgh, City of, EH4 2XU, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 41037024 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Interventions

islatravir; doravirine

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2020
• First Posted: January 18, 2020
• Study Start: March 18, 2020
• Primary Completion: November 21, 2022
• Study Completion: November 1, 2023
• Last Updated: December 27, 2024
• Results First Posted: December 8, 2023

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

PR (1); ZA (4); ES (4); CO (2); PT (5); CA (5); PE (3); DE (6); AU (5); JP (1); CL (3); US (19); FR (11); UA (8); KR (3); IT (9); GB (2); RU (7)