HIV-1 Infection Clinical Trial
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
| Verified date | November 2023 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 501 |
| Est. completion date | October 1, 2025 |
| Est. primary completion date | October 30, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| 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 | Holdsworth House Medical Practice ( Site 4200) | Darlinghurst | New South Wales |
| Australia | Prahran Market Clinic ( Site 4202) | Melbourne | Victoria |
| Australia | St Vincent's Hospital-IBAC ( Site 4203) | Sydney | New South Wales |
| Canada | 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 | Clinique Medicale lActuel-Clinical Research ( Site 3100) | Montreal | Quebec |
| Canada | Maple Leaf Research ( Site 3103) | Toronto | Ontario |
| Canada | Toronto General Hospital ( Site 3102) | Toronto | Ontario |
| Colombia | Ciensalud Ips S A S ( Site 3300) | Barranquilla | Atlantico |
| Colombia | Clinica de la Costa S.A.S. ( Site 3305) | Barranquilla | Atlantico |
| Colombia | Fundacion Valle del Lili- CIC ( Site 3302) | Cali | Valle Del Cauca |
| Japan | National Hospital Organization Nagoya Medical Center ( Site 4403) | Nagoya | Aichi |
| Japan | Tokyo Medical University Hospital ( Site 4404) | Shinjuku-ku | Tokyo |
| Japan | Center Hospital of the National Center for Global Health and Medicine ( Site 4401) | Shinjyuku-ku | Tokyo |
| South Africa | Josha Research ( Site 3903) | Bloemfontein | Free State |
| South Africa | Desmond Tutu Health Foundation ( Site 3902) | Cape Town | Western Cape |
| South Africa | Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 3908) | Cape Town | Western Cape |
| South Africa | Wentworth Hospital ( Site 3904) | Durban | Kwazulu-Natal |
| South Africa | Ezintsha-Clinical Research Site ( Site 3907) | Johannesburg | Gauteng |
| South Africa | Helen Joseph Hospital ( Site 3910) | Johannesburg | Gauteng |
| South Africa | Perinatal HIV Research Unit (PHRU)-Adult Treatment and Research ( Site 3905) | Johannesburg | Gauteng |
| South Africa | Be Part Yoluntu Centre ( Site 3901) | Paarl | Western Cape |
| South Africa | Private Practice Dr. Marleen de Jager ( Site 3900) | Pretoria | Gauteng |
| Switzerland | University Hospital Basel-Infectiology ( Site 4002) | Basel | Basel-Stadt |
| Switzerland | Inselspital Bern-Inselspital Infektiologie ( Site 4003) | Berne | |
| Switzerland | Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 4004) | Genève | Geneve |
| Switzerland | CHUV (centre hospitalier universitaire vaudois) ( Site 4006) | Lausanne | Vaud |
| Switzerland | Ospedale Regionale di Lugano, Sede Civico-Servizio Malattie Infettive ( Site 4005) | Lugano | Ticino |
| Switzerland | UniversitätsSpital Zürich ( Site 4000) | Zürich | Zurich |
| United Kingdom | Heartlands Hospital ( Site 4102) | Birmingham | |
| United Kingdom | North Manchester General Hospital ( Site 4107) | Crumpsall | England |
| United Kingdom | Brighton and Sussex University Hospitals NHS Trust ( Site 4104) | East Sussex | Brighton And Hove |
| United Kingdom | King's College Hospital ( Site 4108) | London | London, City Of |
| United Kingdom | Royal Free Hospital ( Site 4101) | London | England |
| United Kingdom | Royal London Hospital ( Site 4100) | London | England |
| United Kingdom | Royal Victoria Infirmary ( Site 4105) | Newcastle upon Tyne | England |
| United States | Central Texas Clinical Research ( Site 3015) | Austin | Texas |
| United States | Infectious Disease Specialists of Atlanta ( Site 3003) | Decatur | Georgia |
| United States | Midway Immunology and Research Center ( Site 3009) | Fort Pierce | Florida |
| United States | ID Care ( Site 3041) | Hillsborough | New Jersey |
| United States | The Crofoot Research Center ( Site 3040) | Houston | Texas |
| United States | DCOL Center for Clinical Research ( Site 3022) | Longview | Texas |
| United States | Kaiser Permanente-Infectious Disease ( Site 3014) | Los Angeles | California |
| United States | Orlando Immunology Center ( Site 3004) | Orlando | Florida |
| United States | Palmtree Clinical Research ( Site 3032) | Palm Springs | California |
| United States | Penn Medicine: University of Pennsylvania Health System-Perelman Center for Advanced Medicine ( Site | Philadelphia | Pennsylvania |
| United States | Zuckerberg San Francisco General Hospital and Trauma Center-UCSF ID Clinical Trials Center ( Site 30 | San Francisco | California |
| United States | CAN Community Health - Sarasota ( Site 3017) | Sarasota | Florida |
| United States | Chatham County Health Department - Chatham CARE Center-Infectious Disease ( Site 3028) | Savannah | Georgia |
| United States | Georgetown University Medical Center ( Site 3006) | Washington | District of Columbia |
| United States | Triple O Research Institute, P.A ( Site 3026) | West Palm Beach | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Australia, Canada, Colombia, Japan, South Africa, Switzerland, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Participants with HIV-1 RNA =50 copies/mL at Week 48 | Percentage of participants with HIV-1 RNA =50 copies/mL at Week 48 | Week 48 | |
| Primary | Participants with one or more AEs at Week 48 | Percentage of participants with one or more AEs from Day 1 up to Week 48 | Up to Week 48 | |
| Primary | Participants with an AE leading to discontinuation of study intervention at Week 48 | Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 48 | Up to Week 48 | |
| Secondary | Participants with HIV-1 RNA <200 copies/mL at Week 48 | Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 | Week 48 | |
| Secondary | Participants with HIV-1 RNA <50 copies/mL at Week 48 | Percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 | Week 48 | |
| Secondary | Participants with HIV-1 RNA <200 copies/mL at Week 96 | Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 | Week 96 | |
| Secondary | Participants with HIV-1 RNA =50 copies/mL at Week 96 | Percentage of participants with HIV-1 RNA =50 copies/mL at Week 96 | Week 96 | |
| Secondary | Participants with HIV-1 RNA <50 copies/mL at Week 96 | Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 | Week 96 | |
| Secondary | Change from Day 1 in cluster of differentiation 4+ (CD4+) T-cell count at Week 48 | Mean change from baseline at Day 1 in CD4+ T-cell count at Week 48 | Baseline at Day 1 and Week 48 | |
| Secondary | Change from Week 48 in CD4+ T-cell count at 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. | Baseline at Week 48 and Week 96 | |
| Secondary | Change from Day 1 in CD4+ T-cell count at 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. | Baseline at Day 1 and Week 96 | |
| Secondary | Participants with viral resistance-associated substitutions | Number of participants with viral resistance-associated substitutions | Up to Week 96 | |
| Secondary | Low density lipoprotein cholesterol (LDL-C) | Mean change from Baseline to Week 48 in fasting LDL-C | Baseline and Week 48 | |
| Secondary | High density lipoprotein cholesterol (HDL-C) | Mean change from baseline to Week 48 in fasting HDL-C | Baseline and Week 48 | |
| Secondary | Participants with one or more AEs at Week 96 | Percentage of participants with one or more AEs from Day 1 up to Week 96 | Up to Week 96 | |
| Secondary | Participants with AEs leading to discontinuation of study intervention at Week 96 | Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 96 | Up to Week 96 | |
| Secondary | Participants with one or more AEs from Week 48 up to Week 96 | Percentage of participants with one or more AEs from Week 48 up to Week 96 | Week 48 up to Week 96 | |
| Secondary | Participants with AEs leading to discontinuation of study intervention from 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 | Week 48 up to Week 96 |
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