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)

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04233879
• Other study ID #: 8591A-020
• Secondary ID: MK-8591A-020jRCT
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 28, 2020
• Est. completion date: March 3, 2025

Study information

• Verified date: October 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 599
• Est. completion date: March 3, 2025
• Est. primary completion date: November 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV-1 Infection
• Infections

Intervention

Drug:
• DOR/ISL
100 mg DOR/0.75 mg ISL FDC tablet taken once daily by mouth.
• BIC/FTC/TAF
BIC/FTC/TAF 50/200/25 mg FDC tablet taken once daily by mouth.
• Placebo to BIC/FTC/TAF
Placebo tablet matched to BIC/FTC/TAF taken by mouth.
• Placebo to DOR/ISL
Placebo tablet matched to DOR/ISL taken by mouth.

Locations

Country	Name	City	State
Argentina	IDEAA Foundation ( Site 5807)	Buenos Aires	Caba
Argentina	Fundación Huesped ( Site 5801)	C.a.b.a	Caba
Argentina	Helios Salud S.A. ( Site 5802)	Ciudad Autonoma de Buenos Aires	Caba
Argentina	Instituto Oulton ( Site 5804)	Cordoba
Argentina	Instituto CAICI ( Site 5803)	Rosario	Santa Fe
Canada	Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 5703)	Hamilton	Ontario
Canada	Clinique Medicale L Actuel ( Site 5714)	Montreal	Quebec
Canada	McGill University Health Center - Research Institute-CVIS Clinical Research Unit ( Site 5702)	Montreal	Quebec
Canada	Toronto General Hospital - University Health Network ( Site 5705)	Toronto	Ontario
Chile	Centro Cardiovascular Cardiosur ( Site 5907)	Santiago	Region M. De Santiago
Chile	Clinica Arauco Salud ( Site 5900)	Santiago	Region M. De Santiago
Chile	Fundacion Arriaran ( Site 5901)	Santiago	Region M. De Santiago
Chile	Hospital Clinico de la Universidad Catolica ( Site 5903)	Santiago	Region M. De Santiago
Chile	Clinica Universidad Catolica del Maule ( Site 5909)	Talca	Maule
Chile	Hospital Dr. Hernan Henriquez Aravena ( Site 5905)	Temuco	Araucania
Colombia	Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 6006)	Bogota	Distrito Capital De Bogota
Colombia	Hospital Universitario San Ignacio ( Site 6005)	Bogota	Distrito Capital De Bogota
Colombia	Fundacion Valle del Lili ( Site 6001)	Cali	Valle Del Cauca
France	Hopital Avicenne ( Site 6102)	Bobigny	Seine-Saint-Denis
France	CHU de Bordeaux. Hopital Pellegrin ( Site 6116)	Bordeaux	Gironde
France	Hopital Francois Mitterrand ( Site 6119)	Dijon	Cote-d Or
France	Hopital de la Croix-Rousse ( Site 6127)	Lyon	Rhone-Alpes
France	Centre Hospitalier Regional du Orleans ( Site 6108)	Orleans	Centre
France	A.P.H. Paris, Hopital Saint Louis ( Site 6114)	Paris
France	A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 6124)	Paris	Ain
France	Hopital Pitie Salpetriere ( Site 6111)	Paris
France	Hopital Saint-Antoine ( Site 6113)	Paris
France	Centre Hospitalier de Tourcoing ( Site 6100)	Tourcoing	Nord
Germany	EPIMED- Ges. f. epidemiolog. u. klin. Forschung in der Medizin mbH ( Site 6208)	Berlin
Germany	Universitaetsklinikum Bonn ( Site 6200)	Bonn	Nordrhein-Westfalen
Germany	Infektiologikum ( Site 6201)	Frankfurt am Main	Hessen
Germany	Universitaetsklinik Freiburg ( Site 6206)	Freiburg	Baden-Wurttemberg
Germany	Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 6210)	Hamburg
Germany	Klinikum der LMU München ( Site 6204)	Muenchen	Bayern
Germany	MVZ Munchen am Goetheplatz ( Site 6202)	Muenchen	Bayern
Israel	Rambam Medical Center ( Site 6701)	Haifa
Israel	Hadassah Ein Kerem Medical Center ( Site 6702)	Jerusalem
Israel	Chaim Sheba Medical Center. ( Site 6704)	Ramat-Gan
Israel	Kaplan Medical Center ( Site 6700)	Rehovot
Israel	Sourasky Medical Center ( Site 6705)	Tel Aviv
Italy	ASST Papa Giovanni XXIII ( Site 6411)	Bergamo	Lombardia
Italy	ASST Fatebenefratelli-Ospedale Sacco ( Site 6400)	Milano
Italy	Azienda Ospedaliera San Paolo ( Site 6403)	Milano
Italy	Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 6401)	Milano
Italy	Salute San Raffaele ( Site 6402)	Milano
Italy	Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 6404)	Modena	Emilia-Romagna
Italy	Ospedale San Gerardo ASST Monza ( Site 6412)	Monza	Monza E Brianza
Italy	A.O.R.N. dei Colli - Ospedale Cotugno ( Site 6407)	Napoli	Campania
Italy	IRCCS Policlinico San Matteo ( Site 6410)	Pavia
Italy	Azienda USL di Pescara-Presidio Ospedaliero di Pescara ( Site 6413)	Pescara
Italy	Istituto Nazionale per Le Malattie Infettive Lazzaro Spallanzani ( Site 6405)	Roma
Italy	Ospedale Amedeo di Savoia ( Site 6414)	Torino	Piemonte
Japan	Kumamoto University Hospital ( Site 6905)	Kumamoto
Japan	National Hospital Organization Nagoya Medical Center ( Site 6903)	Nagoya	Aichi
Japan	National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 69	Osaka
Japan	Center Hospital of the National Center for Global Health and Medicine ( Site 6901)	Tokyo
Japan	Tokyo Medical University Hospital ( Site 6904)	Tokyo
South Africa	JOSHA Research ( Site 6605)	Bloemfontein	Free State
South Africa	Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 6613)	Cape Town	Western Cape
South Africa	Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 6617)	Cape Town	Western Cape
South Africa	Wentworth Hospital ( Site 6607)	Durban	Kwazulu-Natal
South Africa	Chris Hani Baragwanath Hospital - ICU ( Site 6608)	Johannesburg	Gauteng
South Africa	Ezintsha ( Site 6609)	Johannesburg	Gauteng
South Africa	Wits Health Consortium. Clinical HIV Research Unit ( Site 6614)	Johannesburg	Gauteng
South Africa	Be Part Yoluntu Centre ( Site 6603)	Mbekweni, Paarl	Western Cape
Spain	Hospital Universitari Germans Trias i Pujol ( Site 6301)	Badalona	Barcelona
Spain	Hospital Clinic i Provincial ( Site 6300)	Barcelona	Cataluna
Spain	Hospital Vall D Hebron ( Site 6302)	Barcelona	Cataluna
Spain	Hospital General de Elche ( Site 6308)	Elche	Alicante
Spain	Hospital Universitari de Bellvitge ( Site 6312)	LHospitalet de Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Maranon ( Site 6303)	Madrid
Spain	Hospital Universitario 12 de Octubre ( Site 6305)	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz ( Site 6307)	Madrid
Spain	Hospital Universitario La Paz ( Site 6304)	Madrid
Spain	Hospital Universitario Virgen de la Victoria ( Site 6309)	Malaga
Taiwan	Kaohsiung Veterans General Hospital ( Site 7102)	Kaohsiung
Taiwan	National Cheng Kung University Hospital ( Site 7101)	Tainan
Taiwan	National Taiwan University Hospital ( Site 7100)	Taipei
United States	Saint Hope Foundation, Inc. ( Site 5629)	Bellaire	Texas
United States	University of Alabama at Birmingham 1917 Research Clinic ( Site 5610)	Birmingham	Alabama
United States	Columbus Regional Research Institute ( Site 5616)	Columbus	Georgia
United States	North Texas ID Consultants, PA ( Site 5604)	Dallas	Texas
United States	Infectious Disease Specialists Of Atlanta PC ( Site 5608)	Decatur	Georgia
United States	Midway Immunology and Research ( Site 5622)	Fort Pierce	Florida
United States	Texas Centers for Infectious Disease Associates P.A. ( Site 5619)	Fort Worth	Texas
United States	Kansas City CARE Clinic ( Site 5607)	Kansas City	Missouri
United States	Ruane Clinical Research Group, Inc. ( Site 5624)	Los Angeles	California
United States	The Kinder Medical Group ( Site 5615)	Miami	Florida
United States	Floridian Clinical Research, LLC ( Site 5625)	Miami Lakes	Florida
United States	Hennepin Healthcare-Hennepin Healthcare-ID ( Site 5633)	Minneapolis	Minnesota
United States	Orlando Immunology Center ( Site 5613)	Orlando	Florida
United States	University of Pennsylvania ( Site 5630)	Philadelphia	Pennsylvania
United States	Pueblo Family Physicians ( Site 5606)	Phoenix	Arizona
United States	CAN Community Health ( Site 5627)	Sarasota	Florida
United States	Triple O Research Institute, P.A. ( Site 5621)	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  Colombia,  France,  Germany,  Israel,  Italy,  Japan,  South Africa,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48	HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott Real Time polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 was presented using the FDA Snapshot missing data approach.	Week 48
Primary	Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48	An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experience an AE was reported.	Up to approximately 48 weeks
Primary	Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48	An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE were reported.	Up to approximately 48 weeks
Secondary	Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96	The percentage of participants with HIV-1 RNA <50 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 will be presented using the FDA Snapshot missing data approach.	Week 96
Secondary	Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144	The percentage of participants with HIV-1 RNA <50 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 144 will be presented using the FDA Snapshot missing data approach.	Week 144
Secondary	Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48	The percentage of participants with HIV-1 RNA <40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 48 will be presented using the FDA Snapshot missing data approach.	Week 48
Secondary	Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48	The percentage of participants with HIV-1 RNA <200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 will be presented using the FDA Snapshot missing data approach.	Week 48
Secondary	Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96	The percentage of participants with HIV-1 RNA <40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 96 will be presented using the FDA Snapshot missing data approach.	Week 96
Secondary	Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96	The percentage of participants with HIV-1 RNA <200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 will be presented using the FDA Snapshot missing data approach.	Week 96
Secondary	Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144	The percentage of participants with HIV-1 RNA <40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 144 will be presented using the FDA Snapshot missing data approach.	Week 144
Secondary	Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144	The percentage of participants with HIV-1 RNA <200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 144 will be presented using the FDA Snapshot missing data approach.	Week 144
Secondary	Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48	Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and 48 weeks by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 48 was presented.	Baseline (Day 1) and Week 48
Secondary	Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 96	Plasma CD4+ T-cell count will be measured in cells/mm^3 for baseline and 96 weeks by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 96 will be presented.	Baseline (Day 1) and Week 96
Secondary	Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 144	Plasma CD4+ T-cell count will be measured in cells/mm^3 for baseline and 144 weeks by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 144 will be presented.	Baseline (Day 1) and Week 144
Secondary	Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48	RASs was defined as participants with confirmed HIV-1 RNA =200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 48 was presented.	Week 48
Secondary	Incidence of Viral RASs at Week 96	RASs was defined as participants with confirmed HIV-1 RNA =200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrate viral RASs at Week 96 will be presented.	Week 96
Secondary	Incidence of Viral RASs at Week 144	RASs was defined as participants with confirmed HIV-1 RNA =200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrate viral RASs at Week 144 will be presented.	Week 144
Secondary	Change From Baseline in Body Weight at Week 48	Body weight was measured at baseline and at Week 48. Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight at Week 48 was presented.	Baseline (Day 1) and Week 48
Secondary	Change From Baseline in Body Weight at Week 96	Body weight was measured at baseline and at Week 96. Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight at Week 96 will be presented.	Baseline (Day 1) and Week 96
Secondary	Change From Baseline in Body Weight at Week 144	Body weight was measured at baseline and at Week 144. Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight at Week 144 will be presented.	Baseline (Day 1) and Week 144
Secondary	Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 156	An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experience an AE will be reported.	Up to approximately 156 weeks
Secondary	Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 156	An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE will be reported.	Up to approximately 156 weeks

External Links

•   Merck Clinical Trials Information