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)

NCT ID: NCT04223791

Last Updated: 2025-03-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

643 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-18

Study Completion Date

2025-02-27

Brief Summary

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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 regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that a switch to 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.

Detailed Description

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Conditions

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HIV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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DOR/ISL

A fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and placebo to Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) for 96 weeks.

Group Type EXPERIMENTAL

DOR/ISL

Intervention Type DRUG

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

Placebo to BIC/FTC/TAF

Intervention Type DRUG

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

BIC/FTC/TAF

50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.

Group Type ACTIVE_COMPARATOR

DOR/ISL

Intervention Type DRUG

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

BIC/FTC/TAF

Intervention Type DRUG

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

Placebo to FDC DOR/ISL

Intervention Type DRUG

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

Interventions

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DOR/ISL

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

Intervention Type DRUG

BIC/FTC/TAF

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

Intervention Type DRUG

Placebo to BIC/FTC/TAF

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

Intervention Type DRUG

Placebo to FDC DOR/ISL

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

Intervention Type DRUG

Other Intervention Names

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MK-8591A Placebo to MK-8591A

Eligibility Criteria

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Inclusion Criteria

* Is HIV-1 positive with plasma Human Immunodeficiency Virus 1 (HIV-1) RNA \<50 copies/mL at screening.
* Has been receiving 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.
* Female is 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.

Exclusion Criteria

* 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 DOR.
* Female expects to conceive or donate eggs at any time during the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Pueblo Family Physicians ( Site 2717)

Phoenix, Arizona, United States

Site Status

Pacific Oaks Medical Group ( Site 2765)

Beverly Hills, California, United States

Site Status

Men's Health Foundation ( Site 2749)

Los Angeles, California, United States

Site Status

Kaiser Permanente Los Angeles Medical Center ( Site 2775)

Los Angeles, California, United States

Site Status

Eisenhower Medical Center ( Site 2744)

Palm Springs, California, United States

Site Status

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

Sacramento, California, United States

Site Status

Zuckerberg San Francisco General Hospital UCSF ( Site 2743)

San Francisco, California, United States

Site Status

Whitman-Walker Clinic ( Site 2728)

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

Site Status

TheraFirst Medical Center ( Site 2742)

Fort Lauderdale, Florida, United States

Site Status

Midway Immunology and Research ( Site 2759)

Ft. Pierce, Florida, United States

Site Status

The Kinder Medical Group ( Site 2739)

Miami, Florida, United States

Site Status

AHF South Beach ( Site 2780)

Miami Beach, Florida, United States

Site Status

Orlando Immunology Center ( Site 2734)

Orlando, Florida, United States

Site Status

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

West Palm Beach, Florida, United States

Site Status

Augusta University ( Site 2752)

Augusta, Georgia, United States

Site Status

Infectious Disease Specialists Of Atlanta PC ( Site 2719)

Decatur, Georgia, United States

Site Status

Mercer University ( Site 2738)

Macon, Georgia, United States

Site Status

Chatham County Health Department ( Site 2731)

Savannah, Georgia, United States

Site Status

Hennepin County Medical Center ( Site 2733)

Minneapolis, Minnesota, United States

Site Status

Kansas City CARE Clinic ( Site 2718)

Kansas City, Missouri, United States

Site Status

ID Care ( Site 2751)

Hillsborough, New Jersey, United States

Site Status

Icahn School of Medicine at Mount Sinai ( Site 2700)

New York, New York, United States

Site Status

Montefiore Einstein Center ( Site 2730)

The Bronx, New York, United States

Site Status

North Texas ID Consultants, PA ( Site 2707)

Dallas, Texas, United States

Site Status

The Crofoot Research Center, Inc. ( Site 2715)

Houston, Texas, United States

Site Status

DCOL Center for Clinical Research ( Site 2769)

Longview, Texas, United States

Site Status

Dr. Peter Shalit, MD ( Site 2770)

Seattle, Washington, United States

Site Status

Multicare Health System ( Site 2713)

Spokane, Washington, United States

Site Status

St Vincent's Hospital ( Site 3807)

Darlinghurst, New South Wales, Australia

Site Status

Taylor Square Private Clinic ( Site 3804)

Darlinghurst, New South Wales, Australia

Site Status

Holdsworth House Medical Practice ( Site 3800)

Sydney, New South Wales, Australia

Site Status

Holdsworth House Medical Practice - Brisbane ( Site 3810)

Brisbane, Queensland, Australia

Site Status

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

Herston, Queensland, Australia

Site Status

The Alfred Hospital ( Site 3802)

Melbourne, Victoria, Australia

Site Status

Prahran Market Clinic (PMC) ( Site 3806)

Melbourne, Victoria, Australia

Site Status

LKH Graz West ( Site 3401)

Graz, Styria, Austria

Site Status

Medical University Vienna ( Site 3402)

Vienna, Vienna, Austria

Site Status

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

Vienna, Vienna, Austria

Site Status

Social Medical Center - Otto Wagner Hospital ( Site 3404)

Vienna, Vienna, Austria

Site Status

Vancouver ID Research and Care Centre Society ( Site 2800)

Vancouver, British Columbia, Canada

Site Status

Hamilton Health Sciences ( Site 2803)

Hamilton, Ontario, Canada

Site Status

Clinique de Medecine Urbaine du Quartier Latin ( Site 2804)

Montreal, Quebec, Canada

Site Status

Clinique Medicale L Actuel ( Site 2814)

Montreal, Quebec, Canada

Site Status

Helsinki University Hospital ( Site 3200)

Helsinki, Uusimaa, Finland

Site Status

Hopital Edouard Herriot ( Site 3126)

Lyon, Ain, France

Site Status

CHU de Nice Hopital Archet 1 ( Site 3103)

Nice, Alpes-Maritimes, France

Site Status

Hopital Europeen Marseille ( Site 3117)

Marseille, Bouches-du-Rhone, France

Site Status

Hopital Foch ( Site 3129)

Suresnes, Hauts-de-Seine, France

Site Status

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

Montpellier, Herault, France

Site Status

CHU Hotel Dieu Nantes ( Site 3120)

Nantes, Loire-Atlantique, France

Site Status

Centre Hospitalier Regional du Orleans ( Site 3108)

Orléans, Loiret, France

Site Status

CHU de Nancy Hopital Brabois Adultes ( Site 3128)

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

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Centre Hospitalier de Tourcoing ( Site 3100)

Tourcoing, Nord, France

Site Status

Hopital Saint-Antoine ( Site 3113)

Paris, , France

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Hopital Pitie Salpetriere ( Site 3111)

Paris, , France

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Hopital Tenon ( Site 3118)

Paris, , France

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

Munich, Bavaria, Germany

Site Status

Klinikum der LMU München ( Site 3004)

Munich, Bavaria, Germany

Site Status

Klinikum rechts der Isar der Technischen Universitat ( Site 3005)

Munich, Bavaria, Germany

Site Status

Infektiologikum ( Site 3001)

Frankfurt am Main, Hesse, Germany

Site Status

Medizinische Hochschule Hannover ( Site 3012)

Hanover, Lower Saxony, Germany

Site Status

Universitaetsklinikum Bonn ( Site 3000)

Bonn, North Rhine-Westphalia, Germany

Site Status

Universitaetsklinikum Essen ( Site 3007)

Essen, North Rhine-Westphalia, Germany

Site Status

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

Berlin, , Germany

Site Status

EPIMED GmbH ( Site 3008)

Berlin, , Germany

Site Status

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

Hamburg, , Germany

Site Status

Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 3010)

Hamburg, , Germany

Site Status

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

Milan, Lombardy, Italy

Site Status

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

Milan, , Italy

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Azienda Ospedaliera San Paolo ( Site 3503)

Milan, , Italy

Site Status

ASST Fatebenefratelli-Ospedale Sacco ( Site 3500)

Milan, , Italy

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

Napoli, , Italy

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National Hospital Organization Nagoya Medical Center ( Site 7203)

Nagoya, Aichi-ken, Japan

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National Hospital Organization Osaka National Hospital ( Site 7202)

Osaka, , Japan

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

Tokyo, , Japan

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CAIMED Center - Ponce School of Medicine ( Site 2903)

Ponce, , Puerto Rico

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Puerto Rico CONCRA ( Site 2904)

Rio Piedras, , Puerto Rico

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Clinical Research Puerto Rico Inc ( Site 2900)

San Juan, , Puerto Rico

Site Status

Hope Clinical Research, Inc. ( Site 2902)

San Juan, , Puerto Rico

Site Status

Hospital Universitari Germans Trias i Pujol ( Site 3601)

Badalona, Barcelona [Barcelona], Spain

Site Status

Hospital Universitari Vall d Hebron ( Site 3602)

Barcelona, Barcelona [Barcelona], Spain

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Hospital Universitari de Bellvitge ( Site 3612)

LHospitalet de Llobregat, Barcelona [Barcelona], Spain

Site Status

Hospital Clinic i Provincial ( Site 3600)

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Maranon ( Site 3603)

Madrid, , Spain

Site Status

Hospital Universitario Infanta Leonor ( Site 3606)

Madrid, , Spain

Site Status

Hospital Universitario Ramon y Cajal ( Site 3611)

Madrid, , Spain

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Hospital 12 de Octubre de Madrid ( Site 3605)

Madrid, , Spain

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Hospital Universitario La Paz ( Site 3604)

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Victoria ( Site 3609)

Málaga, , Spain

Site Status

Countries

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United States Australia Austria Canada Finland France Germany Italy Japan Puerto Rico Spain

References

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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.

Reference Type RESULT
PMID: 38734016 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

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MK-8591A-018

Identifier Type: OTHER

Identifier Source: secondary_id

205166

Identifier Type: REGISTRY

Identifier Source: secondary_id

2019-000587-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8591A-018

Identifier Type: -

Identifier Source: org_study_id

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