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)

Phase 3

Active, not recruiting

• Conditions: HIV-1 Infection
• Interventions: Drug: DOR/ISL; Drug: ART

• Registration Number: NCT05631093
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2022-11-18
• Study First Submitted QC: 2022-11-18
• Study First Posted: 2022-11-30
• Study Start: 2023-02-20
• Primary Completion: 2024-10-10
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-07
• Last Update Posted: 2024-11-08
• Study Completion: 2028-07-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 553

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DOR/ISL	DOR/ISL	Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months on a stable oral ART are treated with DOR/ISL for 144 weeks. Participants will have the option to continue in an optional study extension and receive DOR/ISL for up to an additional 96 weeks or until DOR/ISL is commercially accessible (whichever comes first).
ART + DOR/ISL	ART	Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months on a stable oral ART are first treated with standard of care (SOC) ART for 48 weeks, followed by 96 weeks of treatment with DOR/ISL Participants will have the option to continue in an optional study extension and receive DOR/ISL for up to an additional 96 weeks or until DOR/ISL is commercially accessible (whichever comes first).
ART + DOR/ISL	DOR/ISL	Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months on a stable oral ART are first treated with standard of care (SOC) ART for 48 weeks, followed by 96 weeks of treatment with DOR/ISL Participants will have the option to continue in an optional study extension and receive DOR/ISL for up to an additional 96 weeks or until DOR/ISL is commercially accessible (whichever comes first).

Primary Outcome Measures

Name	Time	Method
Participants with HIV-1 RNA ≥50 copies/mL at Week 48	Week 48	Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48
Participants with one or more AEs at Week 48	Up to Week 48	Percentage of participants with one or more AEs from Day 1 up to Week 48
Participants with an AE leading to discontinuation of study intervention at Week 48	Up to Week 48	Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 48

Secondary Outcome Measures

Name	Time	Method
Participants with HIV-1 RNA ≥50 copies/mL at Week 144	Week 144	Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144
Participants with HIV-1 RNA <50 copies/mL at Week 48	Week 48	Percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48
Change from Week 48 in CD4+ T-cell count at Week 144	Baseline at Week 48 and Week 144	Mean change from baseline at Week 48 in CD4+ T-cell count at Week 144. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.
Low density lipoprotein cholesterol (LDL-C)	Baseline and Week 48	Mean change from Baseline to Week 48 in fasting LDL-C
Participants with HIV-1 RNA <200 copies/mL at Week 48	Week 48	Percentage of participants with HIV-1 RNA \<200 copies/mL at Week 48
Participants with HIV-1 RNA <200 copies/mL at Week 144	Week 144	Percentage of participants with HIV-1 RNA \<200 copies/mL at Week 144
Participants with HIV-1 RNA <50 copies/mL at Week 144	Week 144	Percentage of participants with HIV-1 RNA \<50 copies/mL at Week 144
Participants with HIV-1 RNA ≥50 copies/mL at Week 96	Week 96	Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96
Change from Day 1 in CD4+ T-cell count at Week 96	Baseline at Day 1 and Week 96	Mean change from baseline at Day 1 in CD4+ T-cell count at Week 96. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.
High density lipoprotein cholesterol (HDL-C)	Baseline and Week 48	Mean change from baseline to Week 48 in fasting HDL-C
Participants with one or more AEs at Week 96	Up to Week 96	Percentage of participants with one or more AEs from Day 1 up to Week 96
Participants with one or more AEs from Week 48 up to Week 144	Week 48 up to Week 144	Percentage of participants with one or more AEs from Week 48 up to Week 144
Participants with HIV-1 RNA <200 copies/mL at Week 96	Week 96	Percentage of participants with HIV-1 RNA \<200 copies/mL at Week 96
Participants with HIV-1 RNA <50 copies/mL at Week 96	Week 96	Percentage of participants with HIV-1 RNA \<50 copies/mL at Week 96
Change from Day 1 in cluster of differentiation 4+ (CD4+) T-cell count at Week 48	Baseline at Day 1 and Week 48	Mean change from baseline at Day 1 in CD4+ T-cell count at Week 48
Participants with AEs leading to discontinuation of study intervention at Week 144	Up to Week 144	Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 144
Change from Day 1 in CD4+ T-cell count at Week 144	Baseline at Day 1 and Week 144	Mean change from baseline at Day 1 in CD4+ T-cell count at Week 144. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.
Participants with AEs leading to discontinuation of study intervention from Week 48 up to Week 144	Week 48 up to Week 144	Percentage of participants with an AE leading to discontinuation of study intervention from Week 48 up to Week 144
Change from Week 48 in CD4+ T-cell count at Week 96	Baseline at Week 48 and Week 96	Mean change from baseline at Week 48 in CD4+ T-cell count at Week 96. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.
Participants with viral resistance-associated substitutions	Up to Week 144	Number of participants with viral resistance-associated substitutions
Participants with one or more AEs at Week 144	Up to Week 144	Percentage of participants with one or more AEs from Day 1 up to Week 144
Participants with AEs leading to discontinuation of study intervention at Week 96	Up to Week 96	Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 96
Participants with AEs leading to discontinuation of study intervention from Week 48 up to Week 96	Week 48 up to Week 96	Percentage of participants with an AE leading to discontinuation of study intervention from Week 48 up to Week 96
Participants with one or more AEs from Week 48 up to Week 96	Week 48 up to Week 96	Percentage of participants with one or more AEs from Week 48 up to Week 96

Trial Locations

Locations (53)

Brighton and Sussex University Hospitals NHS Trust ( Site 4104); 🇬🇧 East Sussex, Brighton And Hove, United Kingdom

University Hospital Basel-Infectiology ( Site 4002); 🇨🇭 Basel, Basel-Stadt, Switzerland

Wentworth Hospital ( Site 3904); 🇿🇦 Durban, Kwazulu-Natal, South Africa

Kaiser Permanente-Infectious Disease ( Site 3014); 🇺🇸 Los Angeles, California, United States

Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 3104); 🇨🇦 Hamilton, Ontario, Canada

Clinique de médecine Urbaine du Quartier Latin ( Site 3101); 🇨🇦 Montreal, Quebec, Canada

National Hospital Organization Nagoya Medical Center ( Site 4403); 🇯🇵 Nagoya, Aichi, Japan

Prahran Market Clinic ( Site 4202); 🇦🇺 Melbourne, Victoria, Australia

UniversitätsSpital Zürich ( Site 4000); 🇨🇭 Zürich, Zurich, Switzerland

Royal London Hospital ( Site 4100); 🇬🇧 London, England, United Kingdom

Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 3908); 🇿🇦 Cape Town, Western Cape, South Africa

Central Texas Clinical Research ( Site 3015); 🇺🇸 Austin, Texas, United States

The Crofoot Research Center ( Site 3040); 🇺🇸 Houston, Texas, United States

CAN Community Health - Sarasota ( Site 3017); 🇺🇸 Sarasota, Florida, United States

DCOL Center for Clinical Research ( Site 3022); 🇺🇸 Longview, Texas, United States

Triple O Research Institute, P.A ( Site 3026); 🇺🇸 West Palm Beach, Florida, United States

Palmtree Clinical Research ( Site 3032); 🇺🇸 Palm Springs, California, United States

Midway Immunology and Research Center ( Site 3009); 🇺🇸 Fort Pierce, Florida, United States

Zuckerberg San Francisco General Hospital and Trauma Center-UCSF ID Clinical Trials Center ( Site 30; 🇺🇸 San Francisco, California, United States

Infectious Disease Specialists of Atlanta ( Site 3003); 🇺🇸 Decatur, Georgia, United States

Orlando Immunology Center ( Site 3004); 🇺🇸 Orlando, Florida, United States

Chatham County Health Department - Chatham CARE Center-Infectious Disease ( Site 3028); 🇺🇸 Savannah, Georgia, United States

Penn Medicine: University of Pennsylvania Health System-Perelman Center for Advanced Medicine ( Site; 🇺🇸 Philadelphia, Pennsylvania, United States

Holdsworth House Medical Practice ( Site 4200); 🇦🇺 Darlinghurst, New South Wales, Australia

Holdsworth House Medical Practice - Brisbane ( Site 4201); 🇦🇺 Brisbane, Queensland, Australia

Royal Brisbane and Women's Hospital-Infectious Diseases Research ( Site 4204); 🇦🇺 Brisbane, Queensland, Australia

St Vincent's Hospital-IBAC ( Site 4203); 🇦🇺 Sydney, New South Wales, Australia

Maple Leaf Research ( Site 3103); 🇨🇦 Toronto, Ontario, Canada

Helen Joseph Hospital ( Site 3910); 🇿🇦 Johannesburg, Gauteng, South Africa

Ezintsha-Clinical Research Site ( Site 3907); 🇿🇦 Johannesburg, Gauteng, South Africa

Perinatal HIV Research Unit (PHRU)-Adult Treatment and Research ( Site 3905); 🇿🇦 Johannesburg, Gauteng, South Africa

Private Practice Dr. Marleen de Jager ( Site 3900); 🇿🇦 Pretoria, Gauteng, South Africa

King's College Hospital ( Site 4108); 🇬🇧 London, London, City Of, United Kingdom

Heartlands Hospital ( Site 4102); 🇬🇧 Birmingham, United Kingdom

Toronto General Hospital ( Site 3102); 🇨🇦 Toronto, Ontario, Canada

Georgetown University Medical Center ( Site 3006); 🇺🇸 Washington, District of Columbia, United States

Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 4004); 🇨🇭 Genève, Geneve, Switzerland

North Manchester General Hospital ( Site 4107); 🇬🇧 Crumpsall, England, United Kingdom

Royal Free Hospital ( Site 4101); 🇬🇧 London, England, United Kingdom

Clinique Medicale lActuel-Clinical Research ( Site 3100); 🇨🇦 Montreal, Quebec, Canada

Clinica de la Costa S.A.S. ( Site 3305); 🇨🇴 Barranquilla, Atlantico, Colombia

CHUV (centre hospitalier universitaire vaudois) ( Site 4006); 🇨🇭 Lausanne, Vaud, Switzerland

Center Hospital of the National Center for Global Health and Medicine ( Site 4401); 🇯🇵 Shinjyuku-ku, Tokyo, Japan

Ospedale Regionale di Lugano, Sede Civico-Servizio Malattie Infettive ( Site 4005); 🇨🇭 Lugano, Ticino, Switzerland

Ciensalud Ips S A S ( Site 3300); 🇨🇴 Barranquilla, Atlantico, Colombia

Inselspital Bern-Inselspital Infektiologie ( Site 4003); 🇨🇭 Berne, Switzerland

ID Care ( Site 3041); 🇺🇸 Hillsborough, New Jersey, United States

Desmond Tutu Health Foundation ( Site 3902); 🇿🇦 Cape Town, Western Cape, South Africa

Royal Victoria Infirmary ( Site 4105); 🇬🇧 Newcastle upon Tyne, England, United Kingdom

Fundacion Valle del Lili- CIC ( Site 3302); 🇨🇴 Cali, Valle Del Cauca, Colombia

Tokyo Medical University Hospital ( Site 4404); 🇯🇵 Shinjuku-ku, Tokyo, Japan

Josha Research ( Site 3903); 🇿🇦 Bloemfontein, Free State, South Africa

Be Part Yoluntu Centre ( Site 3901); 🇿🇦 Paarl, Western Cape, South Africa