Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018)

HIV Infection Clinical Trial

Official title:

A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04223791
• Other study ID #: 8591A-018
• Secondary ID: MK-8591A-0182051
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 18, 2020
• Est. completion date: February 25, 2025

Study information

• Verified date: February 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with BIC/FTC/TAF as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48. Participants who benefit from their assigned intervention (as determined by investigator) will be able to continue treatment through a 24-week study extension.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 643
• Est. completion date: February 25, 2025
• Est. primary completion date: August 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Is HIV-1 positive with plasma Human Immunodeficiency Virus 1 (HIV-1) RNA <50 copies/mL at screening.
• Has been receiving BIC/FTC/TAF therapy with documented viral suppression (HIV-1 RNA <50 copies/mL) for =3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen.
• Female is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP); is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle; 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; if a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

Exclusion Criteria:

• Has HIV-2 infection.
• Has an active diagnosis of hepatitis due to any cause, including active Hepatitis B Virus (HBV) co-infection.
• 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.
• Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies.
• 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 treatment period.
• Has a documented or known virologic resistance to DOR.
• Female expects to conceive or donate eggs at any time during the study.

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Drug:
• DOR/ISL
100 mg DOR/ 0.75 ISL FDC tablet taken orally once daily
• BIC/FTC/TAF
50 mg BIC, 200 mg FTC, and 25 mg TAF combined in a single tablet, taken orally once daily
• Placebo to BIC/FTC/TAF
Placebo to BIC/FTC/TAF in a single tablet taken orally, once daily
• Placebo to FDC DOR/ISL
Placebo to FDC DOR/ISL in a tablet taken orally, once daily

Locations

Country	Name	City	State
Australia	Holdsworth House Medical Practice - Brisbane ( Site 3810)	Brisbane	Queensland
Australia	St Vincent's Hospital ( Site 3807)	Darlinghurst	New South Wales
Australia	Taylor Square Private Clinic ( Site 3804)	Darlinghurst	New South Wales
Australia	Royal Brisbane and Womens Hospital- Infectious Diseases Unit ( Site 3812)	Herston	Queensland
Australia	Prahran Market Clinic (PMC) ( Site 3806)	Melbourne	Victoria
Australia	The Alfred Hospital ( Site 3802)	Melbourne	Victoria
Australia	Holdsworth House Medical Practice ( Site 3800)	Sydney	New South Wales
Austria	LKH Graz West ( Site 3401)	Graz	Steiermark
Austria	Medical University Vienna ( Site 3402)	Vienna	Wien
Austria	Social Medical Center - Otto Wagner Hospital ( Site 3404)	Vienna	Wien
Austria	Sozialmedizinisches Zentrum Sued - Kaiser-Franz-Josef-Spital ( Site 3400)	Vienna	Wien
Canada	Hamilton Health Sciences ( Site 2803)	Hamilton	Ontario
Canada	Clinique de Medecine Urbaine du Quartier Latin ( Site 2804)	Montreal	Quebec
Canada	Clinique Medicale L Actuel ( Site 2814)	Montreal	Quebec
Canada	Vancouver ID Research and Care Centre Society ( Site 2800)	Vancouver	British Columbia
Finland	Helsinki University Hospital ( Site 3200)	Helsinki	Uusimaa
France	Hopital Edouard Herriot ( Site 3126)	Lyon	Ain
France	Hopital Europeen Marseille ( Site 3117)	Marseille	Bouches-du-Rhone
France	CHU de Montpellier - Hopital Saint-Eloi ( Site 3121)	Montpellier	Herault
France	CHU Hotel Dieu Nantes ( Site 3120)	Nantes	Loire-Atlantique
France	CHU de Nice Hopital Archet 1 ( Site 3103)	Nice	Alpes-Maritimes
France	Centre Hospitalier Regional du Orleans ( Site 3108)	Orleans	Loiret
France	Hopital Pitie Salpetriere ( Site 3111)	Paris
France	Hopital Saint-Antoine ( Site 3113)	Paris
France	Hopital Tenon ( Site 3118)	Paris
France	Hopital Foch ( Site 3129)	Suresnes	Hauts-de-Seine
France	Centre Hospitalier de Tourcoing ( Site 3100)	Tourcoing	Nord
France	CHU de Nancy Hopital Brabois Adultes ( Site 3128)	Vandoeuvre les Nancy	Meurthe-et-Moselle
Germany	EPIMED GmbH ( Site 3008)	Berlin
Germany	ZIBP-Zentrum fur Infektiologie Berlin Prenzlauer Berg GmbH ( Site 3003)	Berlin
Germany	Universitaetsklinikum Bonn ( Site 3000)	Bonn	Nordrhein-Westfalen
Germany	Universitaetsklinikum Essen ( Site 3007)	Essen	Nordrhein-Westfalen
Germany	Infektiologikum ( Site 3001)	Frankfurt am Main	Hessen
Germany	ICH Study Center GmbH & Co.KG ( Site 3009)	Hamburg
Germany	Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 3010)	Hamburg
Germany	Medizinische Hochschule Hannover ( Site 3012)	Hannover	Niedersachsen
Germany	Klinikum der LMU München ( Site 3004)	Muenchen	Bayern
Germany	Klinikum rechts der Isar der Technischen Universitat ( Site 3005)	Muenchen	Bayern
Germany	MVZ Karlsplatz Dr.med.Hans Jaeger ( Site 3002)	Muenchen	Bayern
Italy	ASST Fatebenefratelli-Ospedale Sacco ( Site 3500)	Milano
Italy	Azienda Ospedaliera San Paolo ( Site 3503)	Milano
Italy	Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 3501)	Milano	Lombardia
Italy	Universita' Vita Salute. Ospedale San Raffaele ( Site 3502)	Milano
Italy	A.O.R.N. dei Colli - Ospedale Cotugno ( Site 3507)	Napoli
Japan	National Hospital Organization Nagoya Medical Center ( Site 7203)	Nagoya	Aichi
Japan	National Hospital Organization Osaka National Hospital ( Site 7202)	Osaka
Japan	Center Hospital of the National Center for Global Health and Medicine ( Site 7201)	Tokyo
Puerto Rico	CAIMED Center - Ponce School of Medicine ( Site 2903)	Ponce
Puerto Rico	Puerto Rico CONCRA ( Site 2904)	Rio Piedras
Puerto Rico	Clinical Research Puerto Rico Inc ( Site 2900)	San Juan
Puerto Rico	Hope Clinical Research, Inc. ( Site 2902)	San Juan
Spain	Hospital Universitari Germans Trias i Pujol ( Site 3601)	Badalona	Barcelona [Barcelona]
Spain	Hospital Clinic i Provincial ( Site 3600)	Barcelona
Spain	Hospital Universitari Vall d Hebron ( Site 3602)	Barcelona	Barcelona [Barcelona]
Spain	Hospital Universitari de Bellvitge ( Site 3612)	LHospitalet de Llobregat	Barcelona [Barcelona]
Spain	Hospital 12 de Octubre de Madrid ( Site 3605)	Madrid
Spain	Hospital General Universitario Gregorio Maranon ( Site 3603)	Madrid
Spain	Hospital Universitario Infanta Leonor ( Site 3606)	Madrid
Spain	Hospital Universitario La Paz ( Site 3604)	Madrid
Spain	Hospital Universitario Ramon y Cajal ( Site 3611)	Madrid
Spain	Hospital Universitario Virgen de la Victoria ( Site 3609)	Malaga
United States	Augusta University ( Site 2752)	Augusta	Georgia
United States	Pacific Oaks Medical Group ( Site 2765)	Beverly Hills	California
United States	Montefiore Einstein Center ( Site 2730)	Bronx	New York
United States	North Texas ID Consultants, PA ( Site 2707)	Dallas	Texas
United States	Infectious Disease Specialists Of Atlanta PC ( Site 2719)	Decatur	Georgia
United States	TheraFirst Medical Center ( Site 2742)	Fort Lauderdale	Florida
United States	Midway Immunology and Research ( Site 2759)	Fort Pierce	Florida
United States	ID Care ( Site 2751)	Hillsborough	New Jersey
United States	The Crofoot Research Center, Inc. ( Site 2715)	Houston	Texas
United States	Kansas City CARE Clinic ( Site 2718)	Kansas City	Missouri
United States	DCOL Center for Clinical Research ( Site 2769)	Longview	Texas
United States	Kaiser Permanente Los Angeles Medical Center ( Site 2775)	Los Angeles	California
United States	Men's Health Foundation ( Site 2749)	Los Angeles	California
United States	Mercer University ( Site 2738)	Macon	Georgia
United States	The Kinder Medical Group ( Site 2739)	Miami	Florida
United States	AHF South Beach ( Site 2780)	Miami Beach	Florida
United States	Hennepin County Medical Center ( Site 2733)	Minneapolis	Minnesota
United States	Icahn School of Medicine at Mount Sinai ( Site 2700)	New York	New York
United States	Orlando Immunology Center ( Site 2734)	Orlando	Florida
United States	Eisenhower Medical Center ( Site 2744)	Palm Springs	California
United States	Pueblo Family Physicians ( Site 2717)	Phoenix	Arizona
United States	University of California, Davis, Division of ID Research ( Site 2702)	Sacramento	California
United States	Zuckerberg San Francisco General Hospital UCSF ( Site 2743)	San Francisco	California
United States	Chatham County Health Department ( Site 2731)	Savannah	Georgia
United States	Dr. Peter Shalit, MD ( Site 2770)	Seattle	Washington
United States	Multicare Health System ( Site 2713)	Spokane	Washington
United States	Whitman-Walker Clinic ( Site 2728)	Washington	District of Columbia
United States	Triple O Research Institute, P.A. ( Site 2755)	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Finland,  France,  Germany,  Italy,  Japan,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) =50 Copies/mL at Week 48	The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA =50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.	Week 48
Primary	Percentage of Participants With One or More Adverse Events (AEs) up to Week 48	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an AE up to week 48 is presented.	Up to 48 weeks
Primary	Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to an AE up to week 48 is presented.	Up to 48 weeks
Secondary	Participants With HIV-1 RNA =50 Copies/mL at Week 96	The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA =50 copies/mL at Week 96 is presented.	Week 96
Secondary	Participants With HIV-1 RNA =50 Copies/mL at Week 144	The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA =50 copies/mL at Week 144 is presented.	Week 144
Secondary	Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48	The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 is presented using the FDA snapshot missing data approach	Week 48
Secondary	Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48	The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 48 is presented using the FDA snapshot missing data approach.	Week 48
Secondary	Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 96	The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 96 is presented.	Week 96
Secondary	Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 144	The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 144 is presented.	Week 144
Secondary	Change From Baseline in Cluster of Differentiation-positive (CD4+) T-cell Count at Week 48	Blood samples were used to measure CD4+ T-cell count. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. Change from baseline in CD4+ T-cell count at week 48 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline.	Baseline and Week 48
Secondary	Change From Baseline in CD4+ T-cell Count at Week 96	Blood samples were used to measure CD4+ T-cell count. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. Change from baseline in CD4+ T-cell count at week 96 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline.	Baseline and Week 96
Secondary	Change From Baseline in CD4+ T-cell Count at Week 144	Blood samples were used to measure CD4+ T-cell count. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. Change from baseline in CD4+ T-cell count at week 144 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline.	Baseline and Week 144
Secondary	Participants With Viral Drug Resistance-associated Substitutions at Week 48	Viral drug resistance is defined as participants with confirmed HIV-1 RNA =400 copies/mL having genotypic or phenotypic evidence of resistance to the study drug administered. The number of participants who demonstrate drug resistance is presented.	Week 48
Secondary	Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96	Viral drug resistance is defined as participants with confirmed HIV-1 RNA =400 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 drug resistance is presented.	Week 96
Secondary	Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 144	Viral drug resistance is defined as participants with confirmed HIV-1 RNA =400 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 drug resistance is presented.	Week 144
Secondary	Change From Baseline in Body Weight at Week 48	Body weight was measured and recorded at baseline and week 48. Participants removed their shoes and wore a single layer of clothing at each measurement. The mean change from baseline in body weight at week 48 is presented.	Baseline and Week 48
Secondary	Change From Baseline in Body Weight at Week 96	Body weight was measured and recorded at baseline and week 96. Participants removed their shoes and wore a single layer of clothing at each measurement.	Baseline and Week 96
Secondary	Change From Baseline in Body Weight at Week 144	Body weight was measured and recorded at baseline and week 144. Participants removed their shoes and wore a single layer of clothing at each measurement.	Baseline and Week 144
Secondary	Percentage of Participants With One or More AEs up to Week 144	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to Week 144
Secondary	Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 144	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to Week 144

External Links

•   Merck Clinical Trials Information