Clinical trial NCT05631093: 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)
Official title: A Phase 3, Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: HIV-1 Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-11-30
Enrollment: 553
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: 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.


Eligibility criteria: Inclusion Criteria:

* Is HIV-1 positive with plasma HIV-1 RNA \<50 copies/mL at screening
* Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) 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 DOR

Primary outcomes:
measure: Participants with HIV-1 RNA ≥50 copies/mL at Week 48
timeFrame: Week 48
measure: Participants with one or more AEs at Week 48
timeFrame: Up to Week 48
measure: Participants with an AE leading to discontinuation of study intervention at Week 48
timeFrame: Up to Week 48
Secondary outcomes:
measure: Participants with HIV-1 RNA <200 copies/mL at Week 48
timeFrame: Week 48
measure: Participants with HIV-1 RNA <50 copies/mL at Week 48
timeFrame: Week 48
measure: Participants with HIV-1 RNA <200 copies/mL at Week 96
timeFrame: Week 96
measure: Participants with HIV-1 RNA <200 copies/mL at Week 144
timeFrame: Week 144
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: 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: Change from Day 1 in cluster of differentiation 4+ (CD4+) T-cell count at Week 48
timeFrame: Baseline at Day 1 and Week 48
measure: Change from Week 48 in CD4+ T-cell count at Week 96
timeFrame: Baseline at Week 48 and Week 96
measure: Change from Week 48 in CD4+ T-cell count at Week 144
timeFrame: Baseline at Week 48 and Week 144
measure: Change from Day 1 in CD4+ T-cell count at Week 96
timeFrame: Baseline at Day 1 and Week 96
measure: Change from Day 1 in CD4+ T-cell count at Week 144
timeFrame: Baseline at Day 1 and Week 144
measure: Participants with viral resistance-associated substitutions
timeFrame: Up to Week 144
measure: Low density lipoprotein cholesterol (LDL-C)
timeFrame: Baseline and Week 48
measure: High density lipoprotein cholesterol (HDL-C)
timeFrame: Baseline and Week 48
measure: Participants with one or more AEs at Week 96
timeFrame: Up to Week 96
measure: Participants with one or more AEs at Week 144
timeFrame: Up to Week 144
measure: Participants with AEs leading to discontinuation of study intervention at Week 96
timeFrame: Up to Week 96
measure: Participants with AEs leading to discontinuation of study intervention at Week 144
timeFrame: Up to Week 144
measure: Participants with one or more AEs from Week 48 up to Week 96
timeFrame: Week 48 up to Week 96
measure: Participants with one or more AEs from Week 48 up to Week 144
timeFrame: Week 48 up to Week 144
measure: Participants with AEs leading to discontinuation of study intervention from Week 48 up to Week 96
timeFrame: Week 48 up to Week 96
measure: Participants with AEs leading to discontinuation of study intervention from Week 48 up to Week 144
timeFrame: Week 48 up to Week 144
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Kaiser Permanente-Infectious Disease ( Site 3014)
state: California
city: Palm Springs
country: United States
facility: Palmtree Clinical Research ( Site 3032)
state: California
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital and Trauma Center-UCSF ID Clinical Trials Center ( Site 30
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center ( Site 3006)
state: District of Columbia
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center ( Site 3009)
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center ( Site 3004)
state: Florida
city: Sarasota
country: United States
facility: CAN Community Health - Sarasota ( Site 3017)
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A ( Site 3026)
state: Florida
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta ( Site 3003)
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department - Chatham CARE Center-Infectious Disease ( Site 3028)
state: Georgia
city: Hillsborough
country: United States
facility: ID Care ( Site 3041)
state: New Jersey
city: Philadelphia
country: United States
facility: Penn Medicine: University of Pennsylvania Health System-Perelman Center for Advanced Medicine ( Site
state: Pennsylvania
city: Austin
country: United States
facility: Central Texas Clinical Research ( Site 3015)
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center ( Site 3040)
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research ( Site 3022)
state: Texas
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice ( Site 4200)
state: New South Wales
city: Sydney
country: Australia
facility: St Vincent's Hospital-IBAC ( Site 4203)
state: New South Wales
city: Brisbane
country: Australia
facility: Holdsworth House Medical Practice - Brisbane ( Site 4201)
state: Queensland
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital-Infectious Diseases Research ( Site 4204)
state: Queensland
city: Melbourne
country: Australia
facility: Prahran Market Clinic ( Site 4202)
state: Victoria
city: Hamilton
country: Canada
facility: Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 3104)
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Research ( Site 3103)
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital ( Site 3102)
state: Ontario
city: Montreal
country: Canada
facility: Clinique de médecine Urbaine du Quartier Latin ( Site 3101)
state: Quebec
city: Montreal
country: Canada
facility: Clinique Medicale lActuel-Clinical Research ( Site 3100)
state: Quebec
city: Barranquilla
country: Colombia
facility: Ciensalud Ips S A S ( Site 3300)
state: Atlantico
city: Barranquilla
country: Colombia
facility: Clinica de la Costa S.A.S. ( Site 3305)
state: Atlantico
city: Cali
country: Colombia
facility: Fundacion Valle del Lili- CIC ( Site 3302)
state: Valle Del Cauca
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center ( Site 4403)
state: Aichi
city: Shinjuku-ku
country: Japan
facility: Tokyo Medical University Hospital ( Site 4404)
state: Tokyo
city: Shinjyuku-ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine ( Site 4401)
state: Tokyo
city: Bloemfontein
country: South Africa
facility: Josha Research ( Site 3903)
state: Free State
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit (PHRU)-Adult Treatment and Research ( Site 3905)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Helen Joseph Hospital ( Site 3910)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Ezintsha-Clinical Research Site ( Site 3907)
state: Gauteng
city: Pretoria
country: South Africa
facility: Private Practice Dr. Marleen de Jager ( Site 3900)
state: Gauteng
city: Durban
country: South Africa
facility: Wentworth Hospital ( Site 3904)
state: Kwazulu-Natal
city: Cape Town
country: South Africa
facility: Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 3908)
state: Western Cape
city: Cape Town
country: South Africa
facility: Desmond Tutu Health Foundation ( Site 3902)
state: Western Cape
city: Paarl
country: South Africa
facility: Be Part Yoluntu Centre ( Site 3901)
state: Western Cape
city: Basel
country: Switzerland
facility: University Hospital Basel-Infectiology ( Site 4002)
state: Basel-Stadt
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 4004)
state: Geneve
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano, Sede Civico-Servizio Malattie Infettive ( Site 4005)
state: Ticino
city: Lausanne
country: Switzerland
facility: CHUV (centre hospitalier universitaire vaudois) ( Site 4006)
state: Vaud
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich ( Site 4000)
state: Zurich
city: Berne
country: Switzerland
facility: Inselspital Bern-Inselspital Infektiologie ( Site 4003)
city: East Sussex
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust ( Site 4104)
state: Brighton And Hove
city: Crumpsall
country: United Kingdom
facility: North Manchester General Hospital ( Site 4107)
state: England
city: London
country: United Kingdom
facility: Royal London Hospital ( Site 4100)
state: England
city: London
country: United Kingdom
facility: Royal Free Hospital ( Site 4101)
state: England
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary ( Site 4105)
state: England
city: London
country: United Kingdom
facility: King's College Hospital ( Site 4108)
state: London, City Of
city: Birmingham
country: United Kingdom
facility: Heartlands Hospital ( Site 4102)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: