Clinical trial NCT05630755: 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)
Official title: A Phase 3, Randomized, Active-Controlled, Double-Blind 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 Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)
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: 514
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 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.


Eligibility criteria: The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of participants who experience adverse events (AEs) through Week 48
timeFrame: Up to Week 48
measure: Percentage of participants who discontinue study intervention due to AEs through Week 48
timeFrame: Up to Week 48
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 <200 copies/mL at Week 48
timeFrame: Week 48
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 <200 copies/mL at Week 96
timeFrame: Week 96
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 <200 copies/mL at Week 144
timeFrame: Week 144
measure: Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144
timeFrame: Week 144
measure: Change from baseline in CD4+ T-cell count at Week 48
timeFrame: Baseline at Day 1 and Week 48
measure: Change from baseline in CD4+ T-cell count at Week 96
timeFrame: Baseline at Day 1 and Week 96
measure: Change from baseline in CD4+ T-cell count at Week 144
timeFrame: Baseline at Day 1 and Week 144
measure: Number of participants with viral drug resistance mutations at Week 48
timeFrame: Week 48
measure: Number of participants with viral drug resistance mutations at Week 96
timeFrame: Week 96
measure: Number of participants with viral drug resistance mutations at Week 144
timeFrame: Week 144
measure: Percentage of participants who experience AEs through Week 144
timeFrame: Up to Week 144
measure: Percentage of participants who discontinue study intervention due to AEs through Week 144
timeFrame: Up to Week 144
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pueblo Family Physicians ( Site 1425)
state: Arizona
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group ( Site 1400)
state: California
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group, Inc ( Site 1414)
state: California
city: Los Angeles
country: United States
facility: Mills Clinical Research ( Site 1433)
state: California
city: Washington
country: United States
facility: Whitman-Walker Institute ( Site 1431)
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center ( Site 1402)
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center ( Site 1401)
state: Florida
city: Miami
country: United States
facility: AHF The Kinder Medical Group ( Site 1426)
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center ( Site 1407)
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A ( Site 1417)
state: Florida
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta ( Site 1403)
state: Georgia
city: Macon
country: United States
facility: Mercer University, Department of Internal Medicine ( Site 1411)
state: Georgia
city: Boston
country: United States
facility: AccessHealth MA ( Site 1419)
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center ( Site 1408)
state: Michigan
city: Kansas City
country: United States
facility: KC CARE Health Center-Clinical Trials ( Site 1422)
state: Missouri
city: Las Vegas
country: United States
facility: Las Vegas Research Center ( Site 1436)
state: Nevada
city: Greensboro
country: United States
facility: Regional Center for Infectious Disease Research ( Site 1435)
state: North Carolina
city: Austin
country: United States
facility: Central Texas Clinical Research ( Site 1413)
state: Texas
city: Bellaire
country: United States
facility: St Hope Foundation ( Site 1410)
state: Texas
city: Dallas
country: United States
facility: Prism Health North Texas, Oak Cliff Health Center ( Site 1409)
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, P.A ( Site 1404)
state: Texas
city: Fort Worth
country: United States
facility: Texas Centers for Infectious Disease Associates ( Site 1406)
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center ( Site 1424)
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research ( Site 1415)
state: Texas
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice ( Site 6200)
state: New South Wales
city: Sydney
country: Australia
facility: St Vincent's Hospital-IBAC ( Site 6203)
state: New South Wales
city: Brisbane
country: Australia
facility: Holdsworth House Medical Practice - Brisbane ( Site 6201)
state: Queensland
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital-Infectious Diseases Research ( Site 6204)
state: Queensland
city: Melbourne
country: Australia
facility: Prahran Market Clinic ( Site 6202)
state: Victoria
city: Temuco
country: Chile
facility: Hospital hernan henriquez aravena de temuco-Unidad de Investigación Clínica ( Site 2205)
state: Araucania
city: Talca
country: Chile
facility: Clinica Universidad Catolica del Maule ( Site 2204)
state: Maule
city: Santiago
country: Chile
facility: Clínica Universidad de Los Andes ( Site 2206)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Universidad de Chile - Hospital Clínico Universidad de Chile-Inmunologia Alergia y VIH ( Site 2200)
state: Region M. De Santiago
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Institute of Allergy, Clinical Immunology, ( Site 4801)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Infecious Disease ( Site 4802)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-HIV unit ( Site 4803)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 4804)
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center ( Site 6603)
state: Aichi
city: Shinjyuku-ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine ( Site 6601)
state: Tokyo
city: Osaka
country: Japan
facility: National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 66
city: Bristol
country: United Kingdom
facility: Southmead Hospital ( Site 5805)
state: Bristol, City Of
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham ( Site 5809)
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital ( Site 5812)
state: England
city: London
country: United Kingdom
facility: Royal London Hospital ( Site 5800)
state: England
city: London
country: United Kingdom
facility: Royal Free Hospital ( Site 5801)
state: England
city: London
country: United Kingdom
facility: Guy's & St Thomas' NHS Foundation Trust ( Site 5808)
state: London, City Of
city: London
country: United Kingdom
facility: The Mortimer Market Centre for Sexual Health and HIV Research ( Site 5810)
state: London, City Of
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales ( Site 5803)
state: Wales
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital ( Site 5813)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: