Clinical trial NCT04223778: Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017)
Official title: A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy
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: 672
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 protocol-specified background antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.


Eligibility criteria: Inclusion Criteria:

* Is HIV-1 positive
* Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) 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 hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
* 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 taking long-acting cabotegravir-rilpivirine
* 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: Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (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 up to Week 48
timeFrame: Up to ~48 Weeks
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL From Week 48 to Week 96
timeFrame: Weeks 48-96 (up to ~48 weeks)
measure: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96
timeFrame: Week 96
measure: Percentage Change From Baseline in CD4+ T-cell Count at Week 48
timeFrame: Baseline and Week 48
measure: Percentage Change From Baseline in CD4+ T-cell Count at Week 96
timeFrame: Baseline and Week 96
measure: Percentage Change From Week 48 in CD4+ T-cell Count at Week 96
timeFrame: Week 48 and Week 96
measure: Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48
timeFrame: Week 48
measure: Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96
timeFrame: Week 96
measure: Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens
timeFrame: Baseline and Week 48
measure: Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens)
timeFrame: Baseline and Week 48
measure: Percentage of Participants With One or More AEs up to Week 96
timeFrame: Up to ~96 Weeks
measure: Percentage of Participants Who Discontinued Study Intervention up to Week 96
timeFrame: Up to ~96 Weeks
measure: Percentage of Participants With One or More AEs From Week 48 to Week 96
timeFrame: Weeks 48-96
measure: Percentage of Participants Who Discontinued Study Intervention From Week 48 to Week 96
timeFrame: Weeks 48-96
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Hospital ( Site 1018)
state: District of Columbia
city: Fort Pierce
country: United States
facility: Midway Immunology and Research ( Site 1030)
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center ( Site 1007)
state: Florida
city: Orlando
country: United States
facility: Bliss Healthcare Services ( Site 1025)
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A. ( Site 1026)
state: Florida
city: Savannah
country: United States
facility: Chatham County Health Department ( Site 1043)
state: Georgia
city: Chicago
country: United States
facility: Northstar Healthcare ( Site 1002)
state: Illinois
city: Kansas City
country: United States
facility: Kansas City CARE Health Center ( Site 1008)
state: Missouri
city: Hillsborough
country: United States
facility: ID Care ( Site 1023)
state: New Jersey
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill ( Site 1042)
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania ( Site 1038)
state: Pennsylvania
city: Bellaire
country: United States
facility: Saint Hope Foundation, Inc. ( Site 1037)
state: Texas
city: Dallas
country: United States
facility: North Texas ID Consultants, PA ( Site 1003)
state: Texas
city: Fort Worth
country: United States
facility: Texas Centers for Infectious Disease Associates P.A. ( Site 1022)
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center, Inc. ( Site 1005)
state: Texas
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice ( Site 2300)
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Womens Hospital- Infectious Diseases Unit ( Site 2309)
state: Queensland
city: Carlton
country: Australia
facility: Melbourne Sexual Health Centre ( Site 2305)
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital ( Site 2301)
state: Western Australia
city: Calgary
country: Canada
facility: Southern Alberta HIV Clinic ( Site 1108)
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver ID Research and Care Centre Society ( Site 1100)
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences ( Site 1103)
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Research ( Site 1112)
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital - University Health Network ( Site 1105)
state: Ontario
city: Montreal
country: Canada
facility: Clinique de Medecine Urbaine du Quartier Latin ( Site 1104)
state: Quebec
city: Montreal
country: Canada
facility: Clinique Medicale L Actuel ( Site 1114)
state: Quebec
city: Temuco
country: Chile
facility: Hospital Dr. Hernan Henriquez Aravena ( Site 1305)
state: Araucania
city: Santiago
country: Chile
facility: Clinica Arauco Salud ( Site 1300)
state: Region Metropolitana De Santiago
city: Santiago
country: Chile
facility: Centro de Investigacion Clinica UC CICUC ( Site 1303)
state: Region Metropolitana De Santiago
city: Cali
country: Colombia
facility: Fundacion Valle del Lili ( Site 1201)
state: Valle Del Cauca
city: Dijon
country: France
facility: Hopital Francois Mitterrand ( Site 2019)
state: Cote-d'Or
city: Bordeaux
country: France
facility: CHU de Bordeaux- Hopital Saint Andre ( Site 2015)
state: Gironde
city: Toulouse
country: France
facility: CHU de Toulouse - Hopital Purpan ( Site 2004)
state: Haute-Garonne
city: Nantes
country: France
facility: CHU Hotel Dieu Nantes ( Site 2020)
state: Loire-Atlantique
city: Lyon
country: France
facility: Hopital de la Croix-Rousse ( Site 2027)
state: Rhone-Alpes
city: Rouen
country: France
facility: CHU de Rouen ( Site 2005)
state: Seine-Maritime
city: Paris
country: France
facility: A.P.H. Paris, Hopital Saint Louis ( Site 2014)
city: Milano
country: Italy
facility: ASST Fatebenefratelli-Ospedale Sacco ( Site 2200)
city: Napoli
country: Italy
facility: A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 2208)
city: Roma
country: Italy
facility: Policlinico Gemelli Instituto di Clinica Chirurgica ( Site 2206)
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center ( Site 2403)
state: Aichi
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital ( Site 2402)
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Komagome Hospital ( Site 2406)
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital ( Site 2404)
city: Tokyo
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine ( Site 2401)
city: Christchurch
country: New Zealand
facility: Christchurch Hospital ( Site 2303)
state: Canterbury
city: Wroclaw
country: Poland
facility: EMC Instytut Medyczny SA Przychodnia przy ul. Lowieckiej we Wroclawiu ( Site 1500)
state: Dolnoslaskie
city: Lodz-Baluty
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. dr. Wladyslawa Bieganskiego ( Site 1503)
state: Lodzkie
city: Warszawa
country: Poland
facility: SP ZOZ Wojewodzki Szpital Zakazny ( Site 1505)
state: Mazowieckie
city: Wroclaw
country: Poland
facility: Wroclawskie Centrum Zdrowia SP ZOZ ( Site 1507)
city: Kemerovo
country: Russian Federation
facility: Kemerovo Regional Center for the Prevention and Control of AIDS ( Site 1713)
state: Kemerovskaya Oblast'
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Center for Prevention and Control of AIDS ( Site 1712)
state: Krasnoyarskiy Kray
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg Center for Prophylactic of AIDS and Inf. Diseases ( Site 1701)
state: Leningradskaya Oblast'
city: Moscow
country: Russian Federation
facility: Federal Scientific Methodological AIDS Prevention and Control Center ( Site 1703)
state: Moskva
city: Moscow
country: Russian Federation
facility: Infectious Clinical Hospital #2 ( Site 1719)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 1700)
state: Sankt-Peterburg
city: Yekaterinburg
country: Russian Federation
facility: Regional Center for Prevent. and Control of AIDS and Inf. Diseases ( Site 1715)
state: Sverdlovskaya Oblast'
city: Kazan
country: Russian Federation
facility: Republican Clinical Hospital of Infectious Diseases n. a. A.F.Agafonov ( Site 1707)
state: Tatarstan, Respublika
city: Bloemfontein
country: South Africa
facility: JOSHA Research ( Site 1406)
state: Free State
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 1414)
state: Western Cape
city: Elche
country: Spain
facility: Hospital General de Elche ( Site 1608)
state: Alicante
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol ( Site 1606)
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial ( Site 1600)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon ( Site 1603)
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor ( Site 1601)
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz ( Site 1602)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 1604)
city: Basel
country: Switzerland
facility: Universitaetsspital Basel ( Site 3302)
state: Basel-Stadt
city: Bern
country: Switzerland
facility: Inselspital Universitaetsspital Bern ( Site 3303)
state: Berne
city: Geneva
country: Switzerland
facility: Hopitaux Universitaires de Geneve HUG. ( Site 3304)
state: Geneve
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen ( Site 3301)
state: Sankt Gallen
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano Civico ( Site 3305)
state: Ticino
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich ( Site 3300)
state: Zurich
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospital NHS Trust ( Site 1908)
state: Brighton And Hove
city: Bristol
country: United Kingdom
facility: Southmead Hospital ( Site 1910)
state: Bristol, City Of
city: London
country: United Kingdom
facility: Royal Free Hospital ( Site 1904)
state: Camden
city: London
country: United Kingdom
facility: Kings College Hospital NHS Foundation Trust ( Site 1907)
state: London, City Of
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital ( Site 1902)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Molina JM, Rizzardini G, Orrell C, Afani A, Calmy A, Oka S, Hinestrosa F, Kumar P, Tebas P, Walmsley S, Grandhi A, Klopfer S, Gendrano I, Eves K, Correll TA, Fox MC, Kim J. Switch to fixed-dose doravirine (100 mg) with islatravir (0.75 mg) once daily in virologically suppressed adults with HIV-1 on antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial. Lancet HIV. 2024 Jun;11(6):e369-e379. doi: 10.1016/S2352-3018(24)00031-6. Epub 2024 May 8.