Clinical trial NCT04233879: Study of Doravirine/Islatravir (DOR/ISL 100 mg/0.75 mg) to Evaluate the Antiretroviral Activity, Safety, and Tolerability in Treatment-Naïve Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-020)
Official title: A Phase 3 Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir Once-Daily in HIV-1 Infected Treatment-Naïve Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-01-18
Enrollment: 599
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 is a phase 3, randomized, controlled, double-blind, multisite clinical study of a once-daily fixed dose combination (FDC) of 100 mg doravirine/0.75 mg islatravir (DOR/ISL \[also known as MK-8591A\]) in treatment-naïve participants with human immunodeficiency virus type-1 (HIV-1) infection. The primary objectives are to evaluate the antiretroviral activity, safety, and tolerability of DOR/ISL compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that DOR/ISL is noninferior or superior to BIC/FTC/TAF treatment based on the percentage of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL at Week 48.

Detailed description: Double-blind treatment with the assigned intervention occurs from Day 1 to Week 96, followed by an open-label portion up to Week 144. Participants who benefit from treatment in the opinion of the Investigator may continue their assigned intervention up to Week 168 (or until they have the option to enroll in a DOR/ISL 100 mg/0.25 mg study, whichever is sooner).

Eligibility criteria: Inclusion Criteria:

* Is human immunodeficiency virus type 1 (HIV-1) positive
* Is naïve to antiretroviral therapy (ART) defined as having received ≤10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection including prevention of mother-to-child transmission up to 1 month prior to screening.
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); 2) Is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis); 3) 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; 4) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required

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 HBV infection (defined as hepatitis B surface antigen \[HBsAg\]-positive or hepatitis B virus deoxyribonucleic acid \[HBV DNA\]-positive)
* 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
* Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study
* Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
* Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapy from 45 days prior to Day 1 through the study intervention period
* 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 intervention period
* Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, or any study intervention
* Has exclusionary laboratory values within 45 days prior to Day 1
* Is female and is expecting 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 Who Experienced an Adverse Event (AE) up to Week 48
timeFrame: Up to approximately 48 weeks
measure: Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48
timeFrame: Up to approximately 48 weeks
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
timeFrame: Week 96
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144
timeFrame: Week 144
measure: Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96
timeFrame: Week 96
measure: Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96
timeFrame: Week 96
measure: Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144
timeFrame: Week 144
measure: Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144
timeFrame: Week 144
measure: Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 96
timeFrame: Baseline (Day 1) and Week 96
measure: Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 144
timeFrame: Baseline (Day 1) and Week 144
measure: Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48
timeFrame: Week 48
measure: Incidence of Viral RASs at Week 96
timeFrame: Week 96
measure: Incidence of Viral RASs at Week 144
timeFrame: Week 144
measure: Change From Baseline in Body Weight at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Body Weight at Week 96
timeFrame: Baseline (Day 1) and Week 96
measure: Change From Baseline in Body Weight at Week 144
timeFrame: Baseline (Day 1) and Week 144
measure: Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 156
timeFrame: Up to approximately 156 weeks
measure: Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 156
timeFrame: Up to approximately 156 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham 1917 Research Clinic ( Site 5610)
state: Alabama
city: Phoenix
country: United States
facility: Pueblo Family Physicians ( Site 5606)
state: Arizona
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group, Inc. ( Site 5624)
state: California
city: Fort Pierce
country: United States
facility: Midway Immunology and Research ( Site 5622)
state: Florida
city: Miami Lakes
country: United States
facility: Floridian Clinical Research, LLC ( Site 5625)
state: Florida
city: Miami
country: United States
facility: The Kinder Medical Group ( Site 5615)
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center ( Site 5613)
state: Florida
city: Sarasota
country: United States
facility: CAN Community Health ( Site 5627)
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A. ( Site 5621)
state: Florida
city: Columbus
country: United States
facility: Columbus Regional Research Institute ( Site 5616)
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists Of Atlanta PC ( Site 5608)
state: Georgia
city: Minneapolis
country: United States
facility: Hennepin Healthcare-Hennepin Healthcare-ID ( Site 5633)
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City CARE Clinic ( Site 5607)
state: Missouri
city: Philadelphia
country: United States
facility: University of Pennsylvania ( Site 5630)
state: Pennsylvania
city: Bellaire
country: United States
facility: Saint Hope Foundation, Inc. ( Site 5629)
state: Texas
city: Dallas
country: United States
facility: North Texas ID Consultants, PA ( Site 5604)
state: Texas
city: Fort Worth
country: United States
facility: Texas Centers for Infectious Disease Associates P.A. ( Site 5619)
state: Texas
city: Buenos Aires
country: Argentina
facility: IDEAA Foundation ( Site 5807)
state: Caba
city: C.a.b.a
country: Argentina
facility: Fundación Huesped ( Site 5801)
state: Caba
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Helios Salud S.A. ( Site 5802)
state: Caba
city: Rosario
country: Argentina
facility: Instituto CAICI ( Site 5803)
state: Santa Fe
city: Cordoba
country: Argentina
facility: Instituto Oulton ( Site 5804)
city: Hamilton
country: Canada
facility: Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 5703)
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital - University Health Network ( Site 5705)
state: Ontario
city: Montreal
country: Canada
facility: Clinique Medicale L Actuel ( Site 5714)
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center - Research Institute-CVIS Clinical Research Unit ( Site 5702)
state: Quebec
city: Temuco
country: Chile
facility: Hospital Dr. Hernan Henriquez Aravena ( Site 5905)
state: Araucania
city: Talca
country: Chile
facility: Clinica Universidad Catolica del Maule ( Site 5909)
state: Maule
city: Santiago
country: Chile
facility: Clinica Arauco Salud ( Site 5900)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Hospital Clinico de la Universidad Catolica ( Site 5903)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Fundacion Arriaran ( Site 5901)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Centro Cardiovascular Cardiosur ( Site 5907)
state: Region M. De Santiago
city: Bogota
country: Colombia
facility: Hospital Universitario San Ignacio ( Site 6005)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 6006)
state: Distrito Capital De Bogota
city: Cali
country: Colombia
facility: Fundacion Valle del Lili ( Site 6001)
state: Valle Del Cauca
city: Paris
country: France
facility: A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 6124)
state: Ain
city: Orleans
country: France
facility: Centre Hospitalier Regional du Orleans ( Site 6108)
state: Centre
city: Dijon
country: France
facility: Hopital Francois Mitterrand ( Site 6119)
state: Cote-d Or
city: Bordeaux
country: France
facility: CHU de Bordeaux. Hopital Pellegrin ( Site 6116)
state: Gironde
city: Tourcoing
country: France
facility: Centre Hospitalier de Tourcoing ( Site 6100)
state: Nord
city: Lyon
country: France
facility: Hopital de la Croix-Rousse ( Site 6127)
state: Rhone-Alpes
city: Bobigny
country: France
facility: Hopital Avicenne ( Site 6102)
state: Seine-Saint-Denis
city: Paris
country: France
facility: A.P.H. Paris, Hopital Saint Louis ( Site 6114)
city: Paris
country: France
facility: Hopital Saint-Antoine ( Site 6113)
city: Paris
country: France
facility: Hopital Pitie Salpetriere ( Site 6111)
city: Freiburg
country: Germany
facility: Universitaetsklinik Freiburg ( Site 6206)
state: Baden-Wurttemberg
city: Muenchen
country: Germany
facility: Klinikum der LMU München ( Site 6204)
state: Bayern
city: Muenchen
country: Germany
facility: MVZ Munchen am Goetheplatz ( Site 6202)
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Infektiologikum ( Site 6201)
state: Hessen
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn ( Site 6200)
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: EPIMED- Ges. f. epidemiolog. u. klin. Forschung in der Medizin mbH ( Site 6208)
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 6210)
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 6701)
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center ( Site 6702)
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center. ( Site 6704)
city: Rehovot
country: Israel
facility: Kaplan Medical Center ( Site 6700)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 6705)
city: Napoli
country: Italy
facility: A.O.R.N. dei Colli - Ospedale Cotugno ( Site 6407)
state: Campania
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 6404)
state: Emilia-Romagna
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII ( Site 6411)
state: Lombardia
city: Monza
country: Italy
facility: Ospedale San Gerardo ASST Monza ( Site 6412)
state: Monza E Brianza
city: Torino
country: Italy
facility: Ospedale Amedeo di Savoia ( Site 6414)
state: Piemonte
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 6401)
city: Milano
country: Italy
facility: Salute San Raffaele ( Site 6402)
city: Milano
country: Italy
facility: Azienda Ospedaliera San Paolo ( Site 6403)
city: Milano
country: Italy
facility: ASST Fatebenefratelli-Ospedale Sacco ( Site 6400)
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo ( Site 6410)
city: Pescara
country: Italy
facility: Azienda USL di Pescara-Presidio Ospedaliero di Pescara ( Site 6413)
city: Roma
country: Italy
facility: Istituto Nazionale per Le Malattie Infettive Lazzaro Spallanzani ( Site 6405)
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center ( Site 6903)
state: Aichi
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital ( Site 6905)
city: Osaka
country: Japan
facility: National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 69
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital ( Site 6904)
city: Tokyo
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine ( Site 6901)
city: Bloemfontein
country: South Africa
facility: JOSHA Research ( Site 6605)
state: Free State
city: Johannesburg
country: South Africa
facility: Chris Hani Baragwanath Hospital - ICU ( Site 6608)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Health Consortium. Clinical HIV Research Unit ( Site 6614)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Ezintsha ( Site 6609)
state: Gauteng
city: Durban
country: South Africa
facility: Wentworth Hospital ( Site 6607)
state: Kwazulu-Natal
city: Cape Town
country: South Africa
facility: Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 6617)
state: Western Cape
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 6613)
state: Western Cape
city: Mbekweni, Paarl
country: South Africa
facility: Be Part Yoluntu Centre ( Site 6603)
state: Western Cape
city: Elche
country: Spain
facility: Hospital General de Elche ( Site 6308)
state: Alicante
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol ( Site 6301)
state: Barcelona
city: LHospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge ( Site 6312)
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Vall D Hebron ( Site 6302)
state: Cataluna
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial ( Site 6300)
state: Cataluna
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon ( Site 6303)
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz ( Site 6307)
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre ( Site 6305)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 6304)
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria ( Site 6309)
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital ( Site 7102)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 7101)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 7100)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: