Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017)

NCT04223778 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 8591A-017MK-8591A-0172051652019-000586-20
• Study Type: interventional
• Target: 672
• Locations: 15 countries
• Sites: 78

Brief 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. 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

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to ~48 Weeks

Secondary Outcomes (19)

• Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48

  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

  Week 96

• Group 1: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96

  Week 96

• Percentage Change From Baseline in CD4+ T-cell Count at Week 48

  Baseline and Week 48

• Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96

  Baseline and Week 96

Study Arms (2)

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.

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.

Drug: DOR/ISL; Drug: ART

Interventions

DOR/ISL DRUG

A FDC of 100 mg DOR/ 0.75 mg ISL taken in tablet form, orally, once daily

Also known as: MK-8591A

Group 1: Doravirine/Islatravir (DOR/ISL); Group 2: Baseline Antiretroviral Therapy (ART)

ART DRUG

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.

Group 2: Baseline Antiretroviral Therapy (ART)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (78)

Georgetown University Hospital ( Site 1018)

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

Location

Midway Immunology and Research ( Site 1030)

Ft. Pierce, Florida, 34982, United States

Location

Orlando Immunology Center ( Site 1007)

Orlando, Florida, 32803, United States

Location

Bliss Healthcare Services ( Site 1025)

Orlando, Florida, 32806, United States

Location

Triple O Research Institute, P.A. ( Site 1026)

West Palm Beach, Florida, 33407, United States

Location

Chatham County Health Department ( Site 1043)

Savannah, Georgia, 31401, United States

Location

Northstar Healthcare ( Site 1002)

Chicago, Illinois, 60657, United States

Location

Kansas City CARE Health Center ( Site 1008)

Kansas City, Missouri, 64111, United States

Location

ID Care ( Site 1023)

Hillsborough, New Jersey, 08844, United States

Location

University of North Carolina at Chapel Hill ( Site 1042)

Chapel Hill, North Carolina, 27599, United States

Location

University of Pennsylvania ( Site 1038)

Philadelphia, Pennsylvania, 19104, United States

Location

Saint Hope Foundation, Inc. ( Site 1037)

Bellaire, Texas, 77401, United States

Location

North Texas ID Consultants, PA ( Site 1003)

Dallas, Texas, 75246, United States

Location

Texas Centers for Infectious Disease Associates P.A. ( Site 1022)

Fort Worth, Texas, 76104, United States

Location

The Crofoot Research Center, Inc. ( Site 1005)

Houston, Texas, 77098, United States

Location

Holdsworth House Medical Practice ( Site 2300)

Sydney, New South Wales, 2010, Australia

Location

Royal Brisbane and Womens Hospital- Infectious Diseases Unit ( Site 2309)

Herston, Queensland, 4029, Australia

Location

Melbourne Sexual Health Centre ( Site 2305)

Carlton, Victoria, 3053, Australia

Location

Fiona Stanley Hospital ( Site 2301)

Murdoch, Western Australia, 6150, Australia

Location

Southern Alberta HIV Clinic ( Site 1108)

Calgary, Alberta, T2R 0X7, Canada

Location

Vancouver ID Research and Care Centre Society ( Site 1100)

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Hamilton Health Sciences ( Site 1103)

Hamilton, Ontario, L8L 2X2, Canada

Location

Maple Leaf Research ( Site 1112)

Toronto, Ontario, M5G 1K2, Canada

Location

Toronto General Hospital - University Health Network ( Site 1105)

Toronto, Ontario, M5G 2N2, Canada

Location

Clinique de Medecine Urbaine du Quartier Latin ( Site 1104)

Montreal, Quebec, H2L 4E9, Canada

Location

Clinique Medicale L Actuel ( Site 1114)

Montreal, Quebec, H2L 4P9, Canada

Location

Hospital Dr. Hernan Henriquez Aravena ( Site 1305)

Temuco, Región de la Araucanía, 4781151, Chile

Location

Clinica Arauco Salud ( Site 1300)

Santiago, Santiago Metropolitan, 7560994, Chile

Location

Centro de Investigacion Clinica UC CICUC ( Site 1303)

Santiago, Santiago Metropolitan, 8330034, Chile

Location

Fundacion Valle del Lili ( Site 1201)

Cali, Valle del Cauca Department, 760032, Colombia

Location

Hopital de la Croix-Rousse ( Site 2027)

Lyon, Auvergne-Rhône-Alpes, 69317, France

Location

Hopital Francois Mitterrand ( Site 2019)

Dijon, Cote-d'Or, 21079, France

Location

CHU de Bordeaux- Hopital Saint Andre ( Site 2015)

Bordeaux, Gironde, 33075, France

Location

CHU de Toulouse - Hopital Purpan ( Site 2004)

Toulouse, Haute-Garonne, 31059, France

Location

CHU Hotel Dieu Nantes ( Site 2020)

Nantes, Loire-Atlantique, 44093, France

Location

CHU de Rouen ( Site 2005)

Rouen, Seine-Maritime, 76031, France

Location

A.P.H. Paris, Hopital Saint Louis ( Site 2014)

Paris, 75010, France

Location

ASST Fatebenefratelli-Ospedale Sacco ( Site 2200)

Milan, 20157, Italy

Location

A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 2208)

Naples, 80131, Italy

Location

Policlinico Gemelli Instituto di Clinica Chirurgica ( Site 2206)

Roma, 00168, Italy

Location

National Hospital Organization Nagoya Medical Center ( Site 2403)

Nagoya, Aichi-ken, 460-0001, Japan

Location

National Hospital Organization Osaka National Hospital ( Site 2402)

Osaka, 540-0006, Japan

Location

Tokyo Metropolitan Komagome Hospital ( Site 2406)

Tokyo, 113-8677, Japan

Location

Tokyo Medical University Hospital ( Site 2404)

Tokyo, 160-0023, Japan

Location

Center Hospital of the National Center for Global Health and Medicine ( Site 2401)

Tokyo, 162-8655, Japan

Location

Christchurch Hospital ( Site 2303)

Christchurch, Canterbury, 8011, New Zealand

Location

EMC Instytut Medyczny SA Przychodnia przy ul. Lowieckiej we Wroclawiu ( Site 1500)

Wroclaw, Lower Silesian Voivodeship, 50-220, Poland

Location

SP ZOZ Wojewodzki Szpital Zakazny ( Site 1505)

Warsaw, Masovian Voivodeship, 01-201, Poland

Location

Wroclawskie Centrum Zdrowia SP ZOZ ( Site 1507)

Wroclaw, 50-136, Poland

Location

Wojewodzki Szpital Specjalistyczny im. dr. Wladyslawa Bieganskiego ( Site 1503)

Lodz-Baluty, Łódź Voivodeship, 91-347, Poland

Location

Kemerovo Regional Center for the Prevention and Control of AIDS ( Site 1713)

Kemerovo, Kemerovo Oblast, 650056, Russia

Location

Krasnoyarsk Regional Center for Prevention and Control of AIDS ( Site 1712)

Krasnoyarsk, Krasnoyarsk Krai, 660049, Russia

Location

Saint Petersburg Center for Prophylactic of AIDS and Inf. Diseases ( Site 1701)

Saint Petersburg, Leningradskaya Oblast', 190020, Russia

Location

Federal Scientific Methodological AIDS Prevention and Control Center ( Site 1703)

Moscow, Moscow, 105275, Russia

Location

Infectious Clinical Hospital #2 ( Site 1719)

Moscow, Moscow, 105275, Russia

Location

FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 1700)

Saint Petersburg, Sankt-Peterburg, 196645, Russia

Location

Regional Center for Prevent. and Control of AIDS and Inf. Diseases ( Site 1715)

Yekaterinburg, Sverdlovsk Oblast, 620102, Russia

Location

Republican Clinical Hospital of Infectious Diseases n. a. A.F.Agafonov ( Site 1707)

Kazan', Tatarstan, Respublika, 420140, Russia

Location

JOSHA Research ( Site 1406)

Bloemfontein, Free State, 9301, South Africa

Location

Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 1414)

Cape Town, Western Cape, 7925, South Africa

Location

Hospital General de Elche ( Site 1608)

Elche, Alicante, 03202, Spain

Location

Hospital Universitari Germans Trias i Pujol ( Site 1606)

Badalona, Barcelona [Barcelona], 08916, Spain

Location

Hospital Clinic i Provincial ( Site 1600)

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Maranon ( Site 1603)

Madrid, 28007, Spain

Location

Hospital Universitario Infanta Leonor ( Site 1601)

Madrid, 28031, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz ( Site 1602)

Madrid, 28040, Spain

Location

Hospital Universitario La Paz ( Site 1604)

Madrid, 28046, Spain

Location

Universitaetsspital Basel ( Site 3302)

Basel, Canton of Basel-City, 4031, Switzerland

Location

Inselspital Universitaetsspital Bern ( Site 3303)

Bern, Canton of Bern, 3010, Switzerland

Location

Hopitaux Universitaires de Geneve HUG. ( Site 3304)

Geneva, Canton of Geneva, 1211, Switzerland

Location

Kantonsspital St. Gallen ( Site 3301)

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

Universitaetsspital Zuerich ( Site 3300)

Zurich, Canton of Zurich, 8091, Switzerland

Location

Ospedale Regionale di Lugano Civico ( Site 3305)

Lugano, Canton Ticino, 6903, Switzerland

Location

Brighton and Sussex University Hospital NHS Trust ( Site 1908)

Brighton, Brighton And Hove, BN2 1ES, United Kingdom

Location

Southmead Hospital ( Site 1910)

Bristol, Bristol, City of, BS10 5NB, United Kingdom

Location

Royal Free Hospital ( Site 1904)

London, Camden, NW3 2QG, United Kingdom

Location

Kings College Hospital NHS Foundation Trust ( Site 1907)

London, London, City of, SE5 9RJ, United Kingdom

Location

North Manchester General Hospital ( Site 1902)

Manchester, M8 5RB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38734015 RESULT

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp and 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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2020
• First Posted: January 10, 2020
• Study Start: February 18, 2020
• Primary Completion: September 8, 2021
• Study Completion: August 26, 2024
• Last Updated: February 18, 2026
• Results First Posted: September 19, 2022

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

PL (4); ZA (2); IT (3); RU (8); GB (5); US (15); AU (4); CL (3); ES (7); CH (6); NZ (1); FR (7); CA (7); JP (5); CO (1)