A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Antiretroviral Therapy (ART) (MK-8591A-051)

NCT ID: NCT05631093

Last Updated: 2025-11-21

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

553 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-20

Study Completion Date

2028-07-11

Brief Summary

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The primary objectives of this study are to evaluate the safety and tolerability of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued baseline antiretroviral therapy (ART), through Week 48; and to evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued baseline ART at Week 48. The primary hypothesis is that DOR/ISL is non-inferior to continued baseline ART, as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48, with a margin of 4 percentage points used to define non-inferiority.

Detailed Description

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Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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DOR/ISL

Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) receive doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).

Group Type EXPERIMENTAL

DOR/ISL

Intervention Type DRUG

Single tablet combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.

ART + DOR/ISL

Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).

Group Type ACTIVE_COMPARATOR

ART

Intervention Type DRUG

Standard of care ART, per approved product list, taken orally

Interventions

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ART

Standard of care ART, per approved product list, taken orally

Intervention Type DRUG

DOR/ISL

Single tablet combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.

Intervention Type DRUG

Other Intervention Names

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MK-8591A

Eligibility Criteria

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Inclusion Criteria

* Is Human Immunodeficiency Virus-1 (HIV-1) positive with plasma HIV-1 Ribonucleic Acid (RNA) \<50 copies/mL at screening
* Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) antiretroviral therapy ART with documented viral suppression (HIV-1 RNA \<50 copies/mL) for ≥3 consecutive months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen
* Female is not a participant of childbearing potential (POCBP); or if a POCBP uses an acceptable contraceptive method or abstains from penile-vaginal intercourse as their preferred and usual lifestyle; has a negative highly sensitive pregnancy test; and whose medical history, menstrual history, and recent sexual activity has been reviewed by the investigator

Exclusion Criteria

* Has HIV-2 infection
* Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
* Has a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening
* Has active hepatitis B virus (HBV) infection
* Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis
* Has a ≤5 years prior history of malignancy
* Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers
* Has taken long-acting HIV therapy at any time
* Is currently participating in or has participated in a clinical study and received (or is receiving) 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 Doravine (DOR)
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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Kaiser Permanente-Infectious Disease ( Site 3014)

Los Angeles, California, United States

Site Status

Palmtree Clinical Research ( Site 3032)

Palm Springs, California, United States

Site Status

Zuckerberg San Francisco General Hospital and Trauma Center-UCSF ID Clinical Trials Center ( Site 30

San Francisco, California, United States

Site Status

Georgetown University Medical Center ( Site 3006)

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

Site Status

Midway Immunology and Research Center ( Site 3009)

Ft. Pierce, Florida, United States

Site Status

Orlando Immunology Center ( Site 3004)

Orlando, Florida, United States

Site Status

CAN Community Health - Sarasota ( Site 3017)

Sarasota, Florida, United States

Site Status

Triple O Research Institute, P.A ( Site 3026)

West Palm Beach, Florida, United States

Site Status

Infectious Disease Specialists of Atlanta ( Site 3003)

Decatur, Georgia, United States

Site Status

Chatham County Health Department - Chatham CARE Center-Infectious Disease ( Site 3028)

Savannah, Georgia, United States

Site Status

ID Care ( Site 3041)

Hillsborough, New Jersey, United States

Site Status

Penn Medicine: University of Pennsylvania Health System-Perelman Center for Advanced Medicine ( Site

Philadelphia, Pennsylvania, United States

Site Status

Central Texas Clinical Research ( Site 3015)

Austin, Texas, United States

Site Status

The Crofoot Research Center ( Site 3040)

Houston, Texas, United States

Site Status

DCOL Center for Clinical Research ( Site 3022)

Longview, Texas, United States

Site Status

Holdsworth House Medical Practice ( Site 4200)

Darlinghurst, New South Wales, Australia

Site Status

St Vincent's Hospital-IBAC ( Site 4203)

Sydney, New South Wales, Australia

Site Status

Holdsworth House Medical Practice - Brisbane ( Site 4201)

Brisbane, Queensland, Australia

Site Status

Royal Brisbane and Women's Hospital-Infectious Diseases Research ( Site 4204)

Brisbane, Queensland, Australia

Site Status

Prahran Market Clinic ( Site 4202)

Melbourne, Victoria, Australia

Site Status

Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 3104)

Hamilton, Ontario, Canada

Site Status

Maple Leaf Research ( Site 3103)

Toronto, Ontario, Canada

Site Status

Toronto General Hospital ( Site 3102)

Toronto, Ontario, Canada

Site Status

Clinique de médecine Urbaine du Quartier Latin ( Site 3101)

Montreal, Quebec, Canada

Site Status

Clinique Medicale lActuel-Clinical Research ( Site 3100)

Montreal, Quebec, Canada

Site Status

Ciensalud Ips S A S ( Site 3300)

Barranquilla, Atlántico, Colombia

Site Status

Clinica de la Costa S.A.S. ( Site 3305)

Barranquilla, Atlántico, Colombia

Site Status

Fundacion Valle del Lili- CIC ( Site 3302)

Cali, Valle del Cauca Department, Colombia

Site Status

National Hospital Organization Nagoya Medical Center ( Site 4403)

Nagoya, Aichi-ken, Japan

Site Status

Tokyo Medical University Hospital ( Site 4404)

Shinjuku-ku, Tokyo, Japan

Site Status

Center Hospital of the National Center for Global Health and Medicine ( Site 4401)

Shinjyuku-ku, Tokyo, Japan

Site Status

Josha Research ( Site 3903)

Bloemfontein, Free State, South Africa

Site Status

Perinatal HIV Research Unit (PHRU)-Adult Treatment and Research ( Site 3905)

Johannesburg, Gauteng, South Africa

Site Status

Helen Joseph Hospital ( Site 3910)

Johannesburg, Gauteng, South Africa

Site Status

Ezintsha-Clinical Research Site ( Site 3907)

Johannesburg, Gauteng, South Africa

Site Status

Private Practice Dr. Marleen de Jager ( Site 3900)

Pretoria, Gauteng, South Africa

Site Status

Wentworth Hospital ( Site 3904)

Durban, KwaZulu-Natal, South Africa

Site Status

Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 3908)

Cape Town, Western Cape, South Africa

Site Status

Desmond Tutu Health Foundation ( Site 3902)

Cape Town, Western Cape, South Africa

Site Status

Be Part Yoluntu Centre ( Site 3901)

Paarl, Western Cape, South Africa

Site Status

University Hospital Basel-Infectiology ( Site 4002)

Basel, Canton of Basel-City, Switzerland

Site Status

Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 4004)

Geneva, Canton of Geneva, Switzerland

Site Status

CHUV (centre hospitalier universitaire vaudois) ( Site 4006)

Lausanne, Canton of Vaud, Switzerland

Site Status

UniversitätsSpital Zürich ( Site 4000)

Zurich, Canton of Zurich, Switzerland

Site Status

Ospedale Regionale di Lugano, Sede Civico-Servizio Malattie Infettive ( Site 4005)

Lugano, Canton Ticino, Switzerland

Site Status

Inselspital Bern-Inselspital Infektiologie ( Site 4003)

Bern, , Switzerland

Site Status

Brighton and Sussex University Hospitals NHS Trust ( Site 4104)

East Sussex, Brighton And Hove, United Kingdom

Site Status

North Manchester General Hospital ( Site 4107)

Crumpsall, England, United Kingdom

Site Status

Royal London Hospital ( Site 4100)

London, England, United Kingdom

Site Status

Royal Free Hospital ( Site 4101)

London, England, United Kingdom

Site Status

Royal Victoria Infirmary ( Site 4105)

Newcastle upon Tyne, England, United Kingdom

Site Status

King's College Hospital ( Site 4108)

London, London, City of, United Kingdom

Site Status

Heartlands Hospital ( Site 4102)

Birmingham, , United Kingdom

Site Status

Countries

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United States Australia Canada Colombia Japan South Africa Switzerland United Kingdom

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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MK-8591A-051

Identifier Type: OTHER

Identifier Source: secondary_id

jRCT2031220698

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1283-3894

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-502127-22-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-502127-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8591A-051

Identifier Type: -

Identifier Source: org_study_id

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