Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018)

NCT04223791 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 8591A-018MK-8591A-0182051662019-000587-23
• Study Type: interventional
• Target: 643
• Locations: 10 countries
• Sites: 85

Brief Summary

This study will evaluate the safety and efficacy of a switch to Doravirine/Islatravir (DOR/ISL) (MK-8591A) (a fixed dose combination of doravirine 100 mg and islatravir 0.75 mg) in participants living with human immunodeficiency virus-1 (HIV-1) virologically suppressed on a regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that a switch to DOR/ISL (MK-8591A) will be non-inferior to continued treatment with BIC/FTC/TAF as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48. Participants who benefit from their assigned intervention (as determined by investigator) will be able to continue treatment through a 24-week study extension.

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) ≥50 Copies/mL at Week 48

  The Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. Per protocol, the primary outcome measure, the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48, is presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.

  Week 48

• Percentage of Participants With One or More Adverse Events (AEs) up to Week 48

  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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an AE up to week 48 is presented.

  Up to 48 weeks

• Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48

  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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to an AE up to week 48 is presented.

  Up to 48 weeks

Secondary Outcomes (19)

• Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96

  Week 96

• Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 144

  Week 144

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

  Week 48

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

  Week 48

• Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96

  Week 96

Study Arms (2)

DOR/ISL

EXPERIMENTAL

Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received a once daily (QD) fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and a placebo to BIC/FTC/TAF for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.

Drug: DOR/ISL; Drug: Placebo to BIC/FTC/TAF

BIC/FTC/TAF

ACTIVE COMPARATOR

Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received once daily (QD) 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to fixed dose combination (FDC) DOR/ISL for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.

Drug: BIC/FTC/TAF; Drug: Placebo to FDC DOR/ISL

Interventions

DOR/ISL DRUG

100 mg DOR/ 0.75 ISL FDC single tablet taken orally once daily

Also known as: MK-8591A

DOR/ISL

Placebo to BIC/FTC/TAF DRUG

Placebo to BIC/FTC/TAF in a single tablet taken orally, once daily

DOR/ISL

Placebo to FDC DOR/ISL DRUG

Placebo to FDC DOR/ISL in a single tablet taken orally, once daily

Also known as: Placebo to MK-8591A

BIC/FTC/TAF

BIC/FTC/TAF DRUG

50 mg BIC, 200 mg FTC, and 25 mg TAF combined in a single tablet, taken orally once daily

BIC/FTC/TAF

Eligibility Criteria

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

You may qualify if:

• Is HIV-1 positive with plasma Human Immunodeficiency Virus 1 (HIV-1) RNA \<50 copies/mL at screening.
• Has been receiving bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) therapy 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 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 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 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 (89)

Pueblo Family Physicians ( Site 2717)

Phoenix, Arizona, 85015, United States

Location

Pacific Oaks Medical Group ( Site 2765)

Beverly Hills, California, 90211, United States

Location

Men's Health Foundation ( Site 2749)

Los Angeles, California, 80069, United States

Location

Kaiser Permanente Los Angeles Medical Center ( Site 2775)

Los Angeles, California, 90027, United States

Location

Eisenhower Medical Center ( Site 2744)

Palm Springs, California, 92264, United States

Location

University of California, Davis, Division of ID Research ( Site 2702)

Sacramento, California, 95811, United States

Location

Zuckerberg San Francisco General Hospital UCSF ( Site 2743)

San Francisco, California, 94110, United States

Location

Whitman-Walker Clinic ( Site 2728)

Washington D.C., District of Columbia, 20009, United States

Location

TheraFirst Medical Center ( Site 2742)

Fort Lauderdale, Florida, 33308, United States

Location

Midway Immunology and Research ( Site 2759)

Ft. Pierce, Florida, 34982, United States

Location

The Kinder Medical Group ( Site 2739)

Miami, Florida, 33133, United States

Location

AHF South Beach ( Site 2780)

Miami Beach, Florida, 33140, United States

Location

Orlando Immunology Center ( Site 2734)

Orlando, Florida, 32803, United States

Location

Triple O Research Institute, P.A. ( Site 2755)

West Palm Beach, Florida, 33407, United States

Location

Augusta University ( Site 2752)

Augusta, Georgia, 30912, United States

Location

Infectious Disease Specialists Of Atlanta PC ( Site 2719)

Decatur, Georgia, 30033, United States

Location

Mercer University ( Site 2738)

Macon, Georgia, 31201, United States

Location

Chatham County Health Department ( Site 2731)

Savannah, Georgia, 31401, United States

Location

Hennepin County Medical Center ( Site 2733)

Minneapolis, Minnesota, 55415, United States

Location

Kansas City CARE Clinic ( Site 2718)

Kansas City, Missouri, 64111, United States

Location

ID Care ( Site 2751)

Hillsborough, New Jersey, 08844, United States

Location

Icahn School of Medicine at Mount Sinai ( Site 2700)

New York, New York, 10029, United States

Location

Montefiore Einstein Center ( Site 2730)

The Bronx, New York, 10467, United States

Location

North Texas ID Consultants, PA ( Site 2707)

Dallas, Texas, 75246, United States

Location

The Crofoot Research Center, Inc. ( Site 2715)

Houston, Texas, 77098, United States

Location

DCOL Center for Clinical Research ( Site 2769)

Longview, Texas, 75605, United States

Location

Dr. Peter Shalit, MD ( Site 2770)

Seattle, Washington, 98104, United States

Location

Multicare Health System ( Site 2713)

Spokane, Washington, 99204, United States

Location

St Vincent's Hospital ( Site 3807)

Darlinghurst, New South Wales, 2010, Australia

Location

Taylor Square Private Clinic ( Site 3804)

Darlinghurst, New South Wales, 2010, Australia

Location

Holdsworth House Medical Practice ( Site 3800)

Sydney, New South Wales, 2010, Australia

Location

Holdsworth House Medical Practice - Brisbane ( Site 3810)

Brisbane, Queensland, 4006, Australia

Location

Royal Brisbane and Womens Hospital- Infectious Diseases Unit ( Site 3812)

Herston, Queensland, 4029, Australia

Location

The Alfred Hospital ( Site 3802)

Melbourne, Victoria, 3004, Australia

Location

Prahran Market Clinic (PMC) ( Site 3806)

Melbourne, Victoria, 3181, Australia

Location

LKH Graz West ( Site 3401)

Graz, Styria, 8020, Austria

Location

Medical University Vienna ( Site 3402)

Vienna, Vienna, 1090, Austria

Location

Sozialmedizinisches Zentrum Sued - Kaiser-Franz-Josef-Spital ( Site 3400)

Vienna, Vienna, 1100, Austria

Location

Social Medical Center - Otto Wagner Hospital ( Site 3404)

Vienna, Vienna, 1145, Austria

Location

Vancouver ID Research and Care Centre Society ( Site 2800)

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Hamilton Health Sciences ( Site 2803)

Hamilton, Ontario, L8L 2X2, Canada

Location

Clinique de Medecine Urbaine du Quartier Latin ( Site 2804)

Montreal, Quebec, H2L 4E9, Canada

Location

Clinique Medicale L Actuel ( Site 2814)

Montreal, Quebec, H2L 4P9, Canada

Location

Helsinki University Hospital ( Site 3200)

Helsinki, Uusimaa, 00029, Finland

Location

Hopital Edouard Herriot ( Site 3126)

Lyon, Ain, 69003, France

Location

CHU de Nice Hopital Archet 1 ( Site 3103)

Nice, Alpes-Maritimes, 06202, France

Location

Hopital Europeen Marseille ( Site 3117)

Marseille, Bouches-du-Rhone, 13003, France

Location

Hopital Foch ( Site 3129)

Suresnes, Hauts-de-Seine, 92151, France

Location

CHU de Montpellier - Hopital Saint-Eloi ( Site 3121)

Montpellier, Herault, 34295, France

Location

CHU Hotel Dieu Nantes ( Site 3120)

Nantes, Loire-Atlantique, 44093, France

Location

Centre Hospitalier Regional du Orleans ( Site 3108)

Orléans, Loiret, 45000, France

Location

CHU de Nancy Hopital Brabois Adultes ( Site 3128)

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54511, France

Location

Centre Hospitalier de Tourcoing ( Site 3100)

Tourcoing, Nord, 59208, France

Location

Hopital Saint-Antoine ( Site 3113)

Paris, 75012, France

Location

Hopital Pitie Salpetriere ( Site 3111)

Paris, 75013, France

Location

Hopital Tenon ( Site 3118)

Paris, 75020, France

Location

MVZ Karlsplatz Dr.med.Hans Jaeger ( Site 3002)

Munich, Bavaria, 80335, Germany

Location

Klinikum der LMU München ( Site 3004)

Munich, Bavaria, 80336, Germany

Location

Klinikum rechts der Isar der Technischen Universitat ( Site 3005)

Munich, Bavaria, 81675, Germany

Location

Infektiologikum ( Site 3001)

Frankfurt am Main, Hesse, 60596, Germany

Location

Medizinische Hochschule Hannover ( Site 3012)

Hanover, Lower Saxony, 30625, Germany

Location

Universitaetsklinikum Bonn ( Site 3000)

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Universitaetsklinikum Essen ( Site 3007)

Essen, North Rhine-Westphalia, 45122, Germany

Location

ZIBP-Zentrum fur Infektiologie Berlin Prenzlauer Berg GmbH ( Site 3003)

Berlin, 10439, Germany

Location

EPIMED GmbH ( Site 3008)

Berlin, 12167, Germany

Location

ICH Study Center GmbH & Co.KG ( Site 3009)

Hamburg, 20146, Germany

Location

Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 3010)

Hamburg, 20246, Germany

Location

Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 3501)

Milan, Lombardy, 20122, Italy

Location

Universita' Vita Salute. Ospedale San Raffaele ( Site 3502)

Milan, 20127, Italy

Location

Azienda Ospedaliera San Paolo ( Site 3503)

Milan, 20142, Italy

Location

ASST Fatebenefratelli-Ospedale Sacco ( Site 3500)

Milan, 20157, Italy

Location

A.O.R.N. dei Colli - Ospedale Cotugno ( Site 3507)

Naples, 80131, Italy

Location

National Hospital Organization Nagoya Medical Center ( Site 7203)

Nagoya, Aichi-ken, 460-0001, Japan

Location

National Hospital Organization Osaka National Hospital ( Site 7202)

Osaka, 540-0006, Japan

Location

Center Hospital of the National Center for Global Health and Medicine ( Site 7201)

Tokyo, 162-8655, Japan

Location

CAIMED Center - Ponce School of Medicine ( Site 2903)

Ponce, 00716, Puerto Rico

Location

Puerto Rico CONCRA ( Site 2904)

Rio Piedras, 00925, Puerto Rico

Location

Clinical Research Puerto Rico Inc ( Site 2900)

San Juan, 00909, Puerto Rico

Location

Hope Clinical Research, Inc. ( Site 2902)

San Juan, 00909, Puerto Rico

Location

Hospital Universitari Germans Trias i Pujol ( Site 3601)

Badalona, Barcelona [Barcelona], 08916, Spain

Location

Hospital Universitari Vall d Hebron ( Site 3602)

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Hospital Universitari de Bellvitge ( Site 3612)

LHospitalet de Llobregat, Barcelona [Barcelona], 08907, Spain

Location

Hospital Clinic i Provincial ( Site 3600)

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Maranon ( Site 3603)

Madrid, 28007, Spain

Location

Hospital Universitario Infanta Leonor ( Site 3606)

Madrid, 28031, Spain

Location

Hospital Universitario Ramon y Cajal ( Site 3611)

Madrid, 28034, Spain

Location

Hospital 12 de Octubre de Madrid ( Site 3605)

Madrid, 28041, Spain

Location

Hospital Universitario La Paz ( Site 3604)

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Victoria ( Site 3609)

Málaga, 29010, Spain

Location

Related Publications (1)

• Mills AM, Rizzardini G, Ramgopal MN, Osiyemi OO, Bogner JR, Hagins DP, Paredes R, Reynes J, Rockstroh JK, Carr A, Su FH, Klopfer SO, Eves K, Plank RM, Correll T, Fox MC. Switch to fixed-dose doravirine (100 mg) with islatravir (0.75 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide: 48-week results of a phase 3, randomised, controlled, double-blind, non-inferiority trial. Lancet HIV. 2024 Jun;11(6):e357-e368. doi: 10.1016/S2352-3018(24)00030-4. Epub 2024 May 8.

  PMID: 38734016 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 & 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 8, 2020
• First Posted: January 10, 2020
• Study Start: February 18, 2020
• Primary Completion: August 26, 2021
• Study Completion: February 27, 2025
• Last Updated: March 27, 2026
• Results First Posted: August 22, 2022

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

PR (4); US (28); AU (7); CA (4); FR (12); IT (5); JP (3); ES (10); FI (1); DE (11)