A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-052)

NCT05630755 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 5 other identifiers: 8591A-052MK-8591A-0522022-502079-49-00jRCT2051230003U1111-1283-0949
• Study Type: interventional
• Target: 514
• Locations: 6 countries
• Sites: 49

Brief Summary

The primary objectives of this study are to evaluate the antiretroviral activity of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) at Week 48; and to evaluate the safety and tolerability of a switch to DOR/ISL compared with continued BIC/FTC/TAF, through Week 48. The primary hypotheses are that (1) DOR/ISL is non-inferior to continued BIC/FTC/TAF, 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; and (2) DOR/ISL is superior to BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (3)

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

  HIV-1 RNA levels in blood samples taken at each visit were measured with a reliable lower limit of quantification of \<50 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 Who Experience Adverse Events (AEs) Through 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 is reported.

  Up to Week 48

• Percentage of Participants Who Discontinue Study Intervention Due to AEs Through 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 is reported.

  Up to Week 48

Secondary Outcomes (16)

• Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48

  Week 48

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

  Week 48

• Change From Baseline in Cluster of Differentiation 4-positive (CD4+) T-cell Count at Week 48

  Baseline at Day 1 and Week 48

• Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48

  Up to Week 48

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

  Week 96

Study Arms (2)

DOR/ISL and Placebo to BIC/FTC/TAF

EXPERIMENTAL

Participants will receive DOR/ISL 100 mg/0.25 mg and Placebo to BIC/FTC/TAF once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may continue on DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).

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

BIC/FTC/TAF and Placebo to DOR/ISL

ACTIVE COMPARATOR

Participants will receive BIC/FTC/TAF 50 mg/200 mg/25 mg and Placebo to DOR/ISL once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may switch to DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).

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

Interventions

DOR/ISL DRUG

DOR/ISL 100 mg/0.25 mg oral tablets once daily

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

DOR/ISL and Placebo to BIC/FTC/TAF

BIC/FTC/TAF DRUG

BIC/FTC/TAF 50 mg/200 mg/25 mg oral tablets once daily

Also known as: Bictegravir/Emtricitabine/Tenofovir Alafenamide

BIC/FTC/TAF and Placebo to DOR/ISL

Placebo to BIC/FTC/TAF DRUG

0 mg oral tablets once daily

DOR/ISL and Placebo to BIC/FTC/TAF

Placebo to DOR/ISL DRUG

0 mg oral tablets once daily

BIC/FTC/TAF and Placebo to DOR/ISL

Eligibility Criteria

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

You may not qualify if:

• Is HIV-1 positive with plasma HIV-1 RNA \<50 copies/mL
• Has been receiving BIC/FTC/TAF therapy 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 participant of childbearing potential, not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration
• Has HIV-2 infection
• 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 with laboratory values consistent with cirrhosis
• Has a history of malignancy ≤5 years prior to providing documented 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 strong and moderate cytochrome P450 3A (CYP3A) inducers
• Has a documented or known virologic resistance to DOR
• Has taken long-acting HIV therapy at any time (e.g., cabotegravir, lenacapavir)
• 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 except those currently enrolled in the comparator arm of an ongoing DOR/ISL study

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (49)

Pueblo Family Physicians ( Site 1425)

Phoenix, Arizona, 85015, United States

Location

Pacific Oaks Medical Group ( Site 1400)

Beverly Hills, California, 90211, United States

Location

Ruane Clinical Research Group, Inc ( Site 1414)

Los Angeles, California, 90036, United States

Location

Mills Clinical Research ( Site 1433)

Los Angeles, California, 90069, United States

Location

Whitman-Walker Institute ( Site 1431)

Washington D.C., District of Columbia, 20005, United States

Location

Therafirst Medical Center ( Site 1402)

Fort Lauderdale, Florida, 33308, United States

Location

Midway Immunology and Research Center ( Site 1401)

Ft. Pierce, Florida, 34982, United States

Location

AHF The Kinder Medical Group ( Site 1426)

Miami, Florida, 33133, United States

Location

Orlando Immunology Center ( Site 1407)

Orlando, Florida, 32803, United States

Location

Triple O Research Institute, P.A ( Site 1417)

West Palm Beach, Florida, 33407, United States

Location

Infectious Disease Specialists of Atlanta ( Site 1403)

Decatur, Georgia, 30033, United States

Location

Mercer University, Department of Internal Medicine ( Site 1411)

Macon, Georgia, 31201, United States

Location

AccessHealth MA ( Site 1419)

Boston, Massachusetts, 02129, United States

Location

Be Well Medical Center ( Site 1408)

Berkley, Michigan, 48072, United States

Location

KC CARE Health Center-Clinical Trials ( Site 1422)

Kansas City, Missouri, 64111, United States

Location

Las Vegas Research Center ( Site 1436)

Las Vegas, Nevada, 89106, United States

Location

Regional Center for Infectious Disease Research ( Site 1435)

Greensboro, North Carolina, 27401, United States

Location

Central Texas Clinical Research ( Site 1413)

Austin, Texas, 78705, United States

Location

St Hope Foundation ( Site 1410)

Bellaire, Texas, 77401, United States

Location

Prism Health North Texas, Oak Cliff Health Center ( Site 1409)

Dallas, Texas, 75205, United States

Location

North Texas Infectious Diseases Consultants, P.A ( Site 1404)

Dallas, Texas, 75246, United States

Location

Texas Centers for Infectious Disease Associates ( Site 1406)

Fort Worth, Texas, 76104, United States

Location

The Crofoot Research Center ( Site 1424)

Houston, Texas, 77098, United States

Location

DCOL Center for Clinical Research ( Site 1415)

Longview, Texas, 75605, United States

Location

Holdsworth House Medical Practice ( Site 6200)

Darlinghurst, New South Wales, 2010, Australia

Location

St Vincent's Hospital-IBAC ( Site 6203)

Sydney, New South Wales, 2010, Australia

Location

Holdsworth House Medical Practice - Brisbane ( Site 6201)

Brisbane, Queensland, 4006, Australia

Location

Royal Brisbane and Women's Hospital-Infectious Diseases Research ( Site 6204)

Brisbane, Queensland, 4029, Australia

Location

Prahran Market Clinic ( Site 6202)

Melbourne, Victoria, 3181, Australia

Location

Clinica Universidad Catolica del Maule ( Site 2204)

Talca, Maule Region, 3465584, Chile

Location

Clínica Universidad de Los Andes ( Site 2206)

Santiago, Region M. de Santiago, 7620001, Chile

Location

Universidad de Chile - Hospital Clínico Universidad de Chile-Inmunologia Alergia y VIH ( Site 2200)

Santiago, Region M. de Santiago, 8380420, Chile

Location

Hospital hernan henriquez aravena de temuco-Unidad de Investigación Clínica ( Site 2205)

Temuco, Región de la Araucanía, 4781151, Chile

Location

Rambam Health Care Campus-Institute of Allergy, Clinical Immunology, ( Site 4801)

Haifa, 3109601, Israel

Location

Hadassah Medical Center-Infecious Disease ( Site 4802)

Jerusalem, 9120, Israel

Location

Sheba Medical Center-HIV unit ( Site 4803)

Ramat Gan, 5262100, Israel

Location

Sourasky Medical Center ( Site 4804)

Tel Aviv, 64239, Israel

Location

National Hospital Organization Nagoya Medical Center ( Site 6603)

Nagoya, Aichi-ken, 460-0001, Japan

Location

Center Hospital of the National Center for Global Health and Medicine ( Site 6601)

Shinjyuku-ku, Tokyo, 162-8655, Japan

Location

National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 66

Osaka, 540-0006, Japan

Location

Southmead Hospital ( Site 5805)

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

Location

Queen Elizabeth Hospital Birmingham ( Site 5809)

Birmingham, England, B15 2TH, United Kingdom

Location

Royal Liverpool University Hospital ( Site 5812)

Liverpool, England, L7 8XP, United Kingdom

Location

Royal London Hospital ( Site 5800)

London, England, E1 1BB, United Kingdom

Location

Royal Free Hospital ( Site 5801)

London, England, NW32QG, United Kingdom

Location

Guy's & St Thomas' NHS Foundation Trust ( Site 5808)

London, London, City of, SE1 9RT, United Kingdom

Location

The Mortimer Market Centre for Sexual Health and HIV Research ( Site 5810)

London, London, City of, WC1E 6JB, United Kingdom

Location

University Hospital of Wales ( Site 5803)

Cardiff, Wales, CF14 4XW, United Kingdom

Location

Royal Berkshire Hospital ( Site 5813)

Reading, RG1 5AN, United Kingdom

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Interventions

doravirine; islatravir; bictegravir, emtricitabine, tenofovir alafenamide, drug combination

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: November 18, 2022
• First Posted: November 30, 2022
• Study Start: February 17, 2023
• Primary Completion: October 25, 2024
• Study Completion (Estimated): August 4, 2028
• Last Updated: November 18, 2025
• Results First Posted: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (24); GB (9); JP (3); AU (5); CL (4); IL (4)