Clinical trial NCT04223791: 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)
Official title: A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-01-10
Enrollment: 643
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) ≥50 Copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of Participants With One or More Adverse Events (AEs) up to Week 48
timeFrame: Up to 48 weeks
measure: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48
timeFrame: Up to 48 weeks
Secondary outcomes:
measure: Participants With HIV-1 RNA ≥50 Copies/mL at Week 96
timeFrame: Week 96
measure: Participants With HIV-1 RNA ≥50 Copies/mL at Week 144
timeFrame: Week 144
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48
timeFrame: Week 48
measure: Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 96
timeFrame: Week 96
measure: Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 144
timeFrame: Week 144
measure: Change From Baseline in Cluster of Differentiation-positive (CD4+) T-cell Count at Week 48
timeFrame: Baseline and Week 48
measure: Change From Baseline in CD4+ T-cell Count at Week 96
timeFrame: Baseline and Week 96
measure: Change From Baseline in CD4+ T-cell Count at Week 144
timeFrame: Baseline and Week 144
measure: Participants With Viral Drug Resistance-associated Substitutions at Week 48
timeFrame: Week 48
measure: Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96
timeFrame: Week 96
measure: Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 144
timeFrame: Week 144
measure: Change From Baseline in Body Weight at Week 48
timeFrame: Baseline and Week 48
measure: Change From Baseline in Body Weight at Week 96
timeFrame: Baseline and Week 96
measure: Change From Baseline in Body Weight at Week 144
timeFrame: Baseline and Week 144
measure: Percentage of Participants With One or More AEs up to Week 144
timeFrame: Up to Week 144
measure: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 144
timeFrame: Up to Week 144
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pueblo Family Physicians ( Site 2717)
state: Arizona
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group ( Site 2765)
state: California
city: Los Angeles
country: United States
facility: Men's Health Foundation ( Site 2749)
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center ( Site 2775)
state: California
city: Palm Springs
country: United States
facility: Eisenhower Medical Center ( Site 2744)
state: California
city: Sacramento
country: United States
facility: University of California, Davis, Division of ID Research ( Site 2702)
state: California
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital UCSF ( Site 2743)
state: California
city: Washington
country: United States
facility: Whitman-Walker Clinic ( Site 2728)
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: TheraFirst Medical Center ( Site 2742)
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research ( Site 2759)
state: Florida
city: Miami Beach
country: United States
facility: AHF South Beach ( Site 2780)
state: Florida
city: Miami
country: United States
facility: The Kinder Medical Group ( Site 2739)
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center ( Site 2734)
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A. ( Site 2755)
state: Florida
city: Augusta
country: United States
facility: Augusta University ( Site 2752)
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists Of Atlanta PC ( Site 2719)
state: Georgia
city: Macon
country: United States
facility: Mercer University ( Site 2738)
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department ( Site 2731)
state: Georgia
city: Minneapolis
country: United States
facility: Hennepin County Medical Center ( Site 2733)
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City CARE Clinic ( Site 2718)
state: Missouri
city: Hillsborough
country: United States
facility: ID Care ( Site 2751)
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Einstein Center ( Site 2730)
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai ( Site 2700)
state: New York
city: Dallas
country: United States
facility: North Texas ID Consultants, PA ( Site 2707)
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center, Inc. ( Site 2715)
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research ( Site 2769)
state: Texas
city: Seattle
country: United States
facility: Dr. Peter Shalit, MD ( Site 2770)
state: Washington
city: Spokane
country: United States
facility: Multicare Health System ( Site 2713)
state: Washington
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital ( Site 3807)
state: New South Wales
city: Darlinghurst
country: Australia
facility: Taylor Square Private Clinic ( Site 3804)
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice ( Site 3800)
state: New South Wales
city: Brisbane
country: Australia
facility: Holdsworth House Medical Practice - Brisbane ( Site 3810)
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Womens Hospital- Infectious Diseases Unit ( Site 3812)
state: Queensland
city: Melbourne
country: Australia
facility: The Alfred Hospital ( Site 3802)
state: Victoria
city: Melbourne
country: Australia
facility: Prahran Market Clinic (PMC) ( Site 3806)
state: Victoria
city: Graz
country: Austria
facility: LKH Graz West ( Site 3401)
state: Steiermark
city: Vienna
country: Austria
facility: Medical University Vienna ( Site 3402)
state: Wien
city: Vienna
country: Austria
facility: Sozialmedizinisches Zentrum Sued - Kaiser-Franz-Josef-Spital ( Site 3400)
state: Wien
city: Vienna
country: Austria
facility: Social Medical Center - Otto Wagner Hospital ( Site 3404)
state: Wien
city: Vancouver
country: Canada
facility: Vancouver ID Research and Care Centre Society ( Site 2800)
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences ( Site 2803)
state: Ontario
city: Montreal
country: Canada
facility: Clinique de Medecine Urbaine du Quartier Latin ( Site 2804)
state: Quebec
city: Montreal
country: Canada
facility: Clinique Medicale L Actuel ( Site 2814)
state: Quebec
city: Helsinki
country: Finland
facility: Helsinki University Hospital ( Site 3200)
state: Uusimaa
city: Lyon
country: France
facility: Hopital Edouard Herriot ( Site 3126)
state: Ain
city: Nice
country: France
facility: CHU de Nice Hopital Archet 1 ( Site 3103)
state: Alpes-Maritimes
city: Marseille
country: France
facility: Hopital Europeen Marseille ( Site 3117)
state: Bouches-du-Rhone
city: Suresnes
country: France
facility: Hopital Foch ( Site 3129)
state: Hauts-de-Seine
city: Montpellier
country: France
facility: CHU de Montpellier - Hopital Saint-Eloi ( Site 3121)
state: Herault
city: Nantes
country: France
facility: CHU Hotel Dieu Nantes ( Site 3120)
state: Loire-Atlantique
city: Orleans
country: France
facility: Centre Hospitalier Regional du Orleans ( Site 3108)
state: Loiret
city: Vandoeuvre les Nancy
country: France
facility: CHU de Nancy Hopital Brabois Adultes ( Site 3128)
state: Meurthe-et-Moselle
city: Tourcoing
country: France
facility: Centre Hospitalier de Tourcoing ( Site 3100)
state: Nord
city: Paris
country: France
facility: Hopital Saint-Antoine ( Site 3113)
city: Paris
country: France
facility: Hopital Pitie Salpetriere ( Site 3111)
city: Paris
country: France
facility: Hopital Tenon ( Site 3118)
city: Muenchen
country: Germany
facility: MVZ Karlsplatz Dr.med.Hans Jaeger ( Site 3002)
state: Bayern
city: Muenchen
country: Germany
facility: Klinikum der LMU München ( Site 3004)
state: Bayern
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der Technischen Universitat ( Site 3005)
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Infektiologikum ( Site 3001)
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover ( Site 3012)
state: Niedersachsen
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn ( Site 3000)
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen ( Site 3007)
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: ZIBP-Zentrum fur Infektiologie Berlin Prenzlauer Berg GmbH ( Site 3003)
city: Berlin
country: Germany
facility: EPIMED GmbH ( Site 3008)
city: Hamburg
country: Germany
facility: ICH Study Center GmbH & Co.KG ( Site 3009)
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 3010)
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 3501)
state: Lombardia
city: Milano
country: Italy
facility: Universita' Vita Salute. Ospedale San Raffaele ( Site 3502)
city: Milano
country: Italy
facility: Azienda Ospedaliera San Paolo ( Site 3503)
city: Milano
country: Italy
facility: ASST Fatebenefratelli-Ospedale Sacco ( Site 3500)
city: Napoli
country: Italy
facility: A.O.R.N. dei Colli - Ospedale Cotugno ( Site 3507)
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center ( Site 7203)
state: Aichi
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital ( Site 7202)
city: Tokyo
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine ( Site 7201)
city: Ponce
country: Puerto Rico
facility: CAIMED Center - Ponce School of Medicine ( Site 2903)
city: Rio Piedras
country: Puerto Rico
facility: Puerto Rico CONCRA ( Site 2904)
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico Inc ( Site 2900)
city: San Juan
country: Puerto Rico
facility: Hope Clinical Research, Inc. ( Site 2902)
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol ( Site 3601)
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron ( Site 3602)
state: Barcelona [Barcelona]
city: LHospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge ( Site 3612)
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial ( Site 3600)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon ( Site 3603)
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor ( Site 3606)
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal ( Site 3611)
city: Madrid
country: Spain
facility: Hospital 12 de Octubre de Madrid ( Site 3605)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 3604)
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria ( Site 3609)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.