Doravirine/Islatravir (DOR/ISL) in Heavily Treatment-Experienced (HTE) Participants for Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-019)

NCT ID: NCT04233216

Last Updated: 2024-12-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-18

Study Completion Date

2023-11-01

Brief Summary

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This is a 2-part, phase 3 clinical study evaluating the antiretroviral activity and safety/tolerability of islatravir (ISL), doravirine (DOR), and a fixed dose combination (FDC) of DOR/ISL (also known as MK-8591A) in heavily treatment-experienced (HTE) participants with human immunodeficiency virus type 1 (HIV-1) infection. It is hypothesized that the percentage of participants receiving DOR/ISL to achieve ≥0.5 log10 decrease in HIV-1 ribonucleic acid (RNA) from study baseline (Day 1) to Day 8 is superior to placebo, each given in combination with failing antiretroviral therapy (ART).

Detailed Description

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Part 1 of this study (Day 1 to Day 7) is the double-blind period in which participants receive either ISL, DOR, DOR/ISL, or placebo. Part 2 of this study (Day 8 to Week 97) is the open-label period in which all participants receive DOR/ISL + optimized background therapy (OBT).

Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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ISL + ART

HTE participants with HIV-1 infection take ISL 0.75 mg once daily (QD) in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL fixed dose combination (FDC) QD + OBT from Day 8 to Week 97.

Group Type EXPERIMENTAL

ISL

Intervention Type DRUG

ISL 0.75 mg capsule taken by mouth.

DOR/ISL

Intervention Type DRUG

100 mg DOR/0.75 mg ISL FDC taken by mouth.

DOR + ART

HTE participants with HIV-1 infection take DOR 100 mg QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.

Group Type EXPERIMENTAL

DOR

Intervention Type DRUG

DOR 100 mg tablet taken by mouth.

DOR/ISL

Intervention Type DRUG

100 mg DOR/0.75 mg ISL FDC taken by mouth.

DOR/ISL + ART

HTE participants with HIV-1 infection take 100 mg DOR/0.75 mg ISL FDC QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.

Group Type EXPERIMENTAL

DOR/ISL

Intervention Type DRUG

100 mg DOR/0.75 mg ISL FDC taken by mouth.

Placebo + ART

HTE participants with HIV-1 infection take placebo QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.

Group Type PLACEBO_COMPARATOR

DOR/ISL

Intervention Type DRUG

100 mg DOR/0.75 mg ISL FDC taken by mouth.

Placebo to ISL

Intervention Type DRUG

Placebo capsule matched to ISL taken by mouth.

Placebo to DOR

Intervention Type DRUG

Placebo tablet matched to DOR taken by mouth.

Interventions

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ISL

ISL 0.75 mg capsule taken by mouth.

Intervention Type DRUG

DOR

DOR 100 mg tablet taken by mouth.

Intervention Type DRUG

DOR/ISL

100 mg DOR/0.75 mg ISL FDC taken by mouth.

Intervention Type DRUG

Placebo to ISL

Placebo capsule matched to ISL taken by mouth.

Intervention Type DRUG

Placebo to DOR

Placebo tablet matched to DOR taken by mouth.

Intervention Type DRUG

Other Intervention Names

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Islatravir MK-8591 Doravirine MK-1439 Doravirine/Islatravir MK-8591A

Eligibility Criteria

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Inclusion Criteria

* Is HIV-1 positive.
* Has been receiving the same baseline ART for ≥3 months prior to signing the Informed Consent Form/Assent Form.
* Weighs ≥35 kg.
* Has at least triple-class resistance (must include nucleoside reverse transcriptase inhibitor \[NRTI\], non-nucleoside reverse transcriptase inhibitor \[NNRTI\], and resistance to either protease inhibitor (PI) or integrase strand transfer inhibitor (InSTI), based on central laboratory-based resistance or proviral DNA resistance testing at the Screening Visit, or historical resistance testing within 12 months of screening.
* Has ≤2 fully active antiretroviral drugs remaining among all antiretroviral classes that can be effectively combined to form a viable regimen based on resistance, tolerability, safety, drug access, or acceptability to participant.
* If female, is not pregnant or breastfeeding, and is: 1) not a woman of childbearing potential (WOCBP); 2) a WOCBP and uses an acceptable method of contraception/is abstinent; or 3) a WOCBP and has a negative pregnancy test within 24 hours of the first dose of study medication.

Exclusion Criteria

* Has HIV type 2 (HIV-2) infection.
* Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator.
* Has hepatitis B virus (HBV) co-infection (defined as hepatitis B surface antigen \[HBsAg\]-positive or HBV deoxyribonucleic acid \[DNA\] positive) and is not currently being treated for HBV.
* Has a history or current evidence of any condition, therapy (including active TB co-infection), laboratory abnormality or other circumstance (including drug or alcohol abuse or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with study participation for the full study duration.
* Is taking or is anticipated to require any of the prohibited therapies from the Screening Visit and throughout the study treatment period.
* Is taking DOR as part of his/her current failing antiretroviral regimen.
* Is taking efavirenz (EFV), etravirine, or nevirapine.
* Is currently participating in or has participated in an interventional clinical study with an investigational compound or device from the Screening Visit through the study treatment period.
* Is female and is expecting to conceive or donate eggs at any time during the study.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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University of Alabama at Birmingham 1917 Research Clinic ( Site 4031)

Birmingham, Alabama, United States

Site Status

Men's Health Foundation ( Site 4018)

Los Angeles, California, United States

Site Status

Palmtree Clinical Research, Inc. ( Site 4016)

Palm Springs, California, United States

Site Status

Yale School of Medicine ( Site 4007)

New Haven, Connecticut, United States

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Georgetown University Hospital ( Site 4015)

Washington D.C., District of Columbia, United States

Site Status

The Kinder Medical Group ( Site 4014)

Miami, Florida, United States

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Orlando Immunology Center ( Site 4012)

Orlando, Florida, United States

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Triple O Research Institute, P.A. ( Site 4020)

West Palm Beach, Florida, United States

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Chatham County Health Department ( Site 4029)

Savannah, Georgia, United States

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Howard Brown Health Center ( Site 4006)

Chicago, Illinois, United States

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Northstar Healthcare ( Site 4004)

Chicago, Illinois, United States

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University of Maryland ( Site 4023)

Baltimore, Maryland, United States

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The University of Mississippi Medical Center ( Site 4036)

Jackson, Mississippi, United States

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Saint Michael's Medical Center-Research - Infectious Disease ( Site 4035)

Newark, New Jersey, United States

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Icahn School of Medicine at Mount Sinai ( Site 4000)

New York, New York, United States

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University of North Carolina at Chapel Hill ( Site 4026)

Chapel Hill, North Carolina, United States

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Saint Hope Foundation, Inc. ( Site 4034)

Bellaire, Texas, United States

Site Status

North Texas Infectious Diseases Consultants, PA ( Site 4005)

Dallas, Texas, United States

Site Status

Dr. Peter Shalit, MD ( Site 4002)

Seattle, Washington, United States

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Holdsworth House Medical Practice ( Site 5300)

Sydney, New South Wales, Australia

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St Vincent's Hospital ( Site 5309)

Sydney, New South Wales, Australia

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Holdsworth House Medical Practice - Brisbane ( Site 5312)

Brisbane, Queensland, Australia

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Monash Health-Monash Medical Centre ( Site 5313)

Clayton, Victoria, Australia

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The Alfred Hospital ( Site 5304)

Melbourne, Victoria, Australia

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Vancouver ID Research and Care Centre Society ( Site 4100)

Vancouver, British Columbia, Canada

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Hamilton Health Sciences ( Site 4115)

Hamilton, Ontario, Canada

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Ottawa Hospital Research Institute ( Site 4111)

Ottawa, Ontario, Canada

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Toronto General Hospital - University Health Network ( Site 4105)

Toronto, Ontario, Canada

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McGill University Health Center - Research Institute-CVIS Clinical Research Unit ( Site 4102)

Montreal, Quebec, Canada

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Fundacion Arriaran ( Site 4401)

Santiago, Region M. de Santiago, Chile

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Centro Cardiovascular Cardiosur ( Site 4407)

Santiago, Region M. de Santiago, Chile

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Hospital Dr. Hernan Henriquez Aravena ( Site 4405)

Temuco, Región de la Araucanía, Chile

Site Status

Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 4306)

Bogotá, Bogota D.C., Colombia

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Fundacion Valle del Lili ( Site 4301)

Cali, Valle del Cauca Department, Colombia

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Hopital Edouard Herriot ( Site 4726)

Lyon, Ain, France

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A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 4724)

Paris, Ain, France

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CHU de Nice Hopital Archet 1 ( Site 4703)

Nice, Alpes-Maritimes, France

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Hopital Europeen Marseille ( Site 4717)

Marseille, Bouches-du-Rhone, France

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CHU de Bordeaux- Hopital Saint Andre ( Site 4715)

Bordeaux, Gironde, France

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CHU de Rouen ( Site 4705)

Rouen, Haute-Normandie, France

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CHU de Montpellier - Hopital Saint-Eloi ( Site 4721)

Montpellier, Herault, France

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Centre Hospitalier de Tourcoing ( Site 4700)

Tourcoing, Nord, France

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Hopital Avicenne ( Site 4702)

Bobigny, Seine-Saint-Denis, France

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Hopital Hotel Dieu [Paris, France] ( Site 4723)

Paris, , France

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A.P.H. Paris, Hopital Saint Louis ( Site 4714)

Paris, , France

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Medizinische Hochschule Hannover ( Site 4612)

Hanover, Lower Saxony, Germany

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Universitaetsklinikum Bonn ( Site 4600)

Bonn, North Rhine-Westphalia, Germany

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Universitaetsklinikum Essen ( Site 4607)

Essen, North Rhine-Westphalia, Germany

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ZIBP-Zentrum fur Infektiologie Berlin Prenzlauer Berg GmbH ( Site 4603)

Berlin, , Germany

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EPIMED GmbH ( Site 4608)

Berlin, , Germany

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ICH Study Center GmbH & Co.KG ( Site 4609)

Hamburg, , Germany

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Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 5004)

Modena, Emilia-Romagna, Italy

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Ospedale San Gerardo ASST Monza ( Site 5012)

Monza, Monza E Brianza, Italy

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Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 5001)

Milan, , Italy

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Universita' Vita Salute. Ospedale San Raffaele ( Site 5002)

Milan, , Italy

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Azienda Ospedaliera San Paolo ( Site 5003)

Milan, , Italy

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ASST Fatebenefratelli-Ospedale Sacco ( Site 5000)

Milan, , Italy

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IRCCS Policlinico San Matteo ( Site 5010)

Pavia, , Italy

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Istituto Nazionale per Le Malattie Infettive Lazzaro Spallanzani ( Site 5005)

Roma, , Italy

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Policlinico Gemelli Instituto di Clinica Chirurgica ( Site 5006)

Roma, , Italy

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Center Hospital of the National Center for Global Health and Medicine ( Site 5401)

Tokyo, , Japan

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INMENSA ( Site 4506)

Lima, Muni Metro de Lima, Peru

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Via Libre ( Site 4500)

Lima, , Peru

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Policlinico Universidad Nacional Mayor de San Marcos ( Site 4501)

Lima, , Peru

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Hospital de Nossa Senhora da Oliveira- EPE ( Site 4905)

Guimarães, Braga District, Portugal

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Hospital Dr. Fernando Fonseca, EPE - Amadora/Sintra ( Site 4902)

Amadora, Lisbon District, Portugal

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Centro Hospitalar de Lisboa Norte Hospital de Santa Maria ( Site 4913)

Lisbon, , Portugal

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Hospital Geral de Santo Antonio ( Site 4908)

Porto, , Portugal

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Centro Hospitalar de Sao Joao. EPE - Hospital de Sao Joao ( Site 4907)

Porto, , Portugal

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HOPE Clinical Research ( Site 5700)

San Juan, , Puerto Rico

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Saint Petersburg Center for Prophylactic of AIDS and Inf. Diseases ( Site 5101)

Saint Petersburg, Leningradskaya Oblast', Russia

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Infectious Clinical Hospital #2 ( Site 5114)

Moscow, Moscow, Russia

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Gbuz Samarskiy Oblastnoy Klinicheskiy Tsentr Profilaktiki I Bor'by So Spid ( Site 5113)

Samara, Samara Oblast, Russia

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FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 5100)

Saint Petersburg, Sankt-Peterburg, Russia

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Smolensk Center On Aids And Infectious Diseases Prophylaxis ( Site 5115)

Smolensk, Smolensk Oblast, Russia

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Regional Center for Prevent. and Control of AIDS and Inf. Diseases ( Site 5106)

Yekaterinburg, Sverdlovsk Oblast, Russia

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Republican Clinical Hospital of Infectious Diseases n. a. A.F.Agafonov ( Site 5104)

Kazan', Tatarstan, Respublika, Russia

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FARMOVS ( Site 4805)

Bloemfontein, Free State, South Africa

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Wits Clinical HIV Research Unit ( Site 4804)

Johannesburg, Gauteng, South Africa

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Ezintsha ( Site 4806)

Johannesburg, Gauteng, South Africa

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King Edward Hospital ( Site 4802)

Durban, KwaZulu-Natal, South Africa

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Pusan National University Hospital ( Site 5503)

Busan, Pusan-Kwangyokshi, South Korea

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Severance Hospital Yonsei University Health System ( Site 5500)

Seoul, , South Korea

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The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 5502)

Seoul, , South Korea

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Hospital Universitari Germans Trias i Pujol ( Site 5600)

Badalona, Barcelona, Spain

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Hospital Clinic i Provincial ( Site 5601)

Barcelona, Catalonia, Spain

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Hospital Santa Lucia ( Site 5603)

Cartagena, Murcia, Region de, Spain

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Hospital Universitario La Paz ( Site 5604)

Madrid, , Spain

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Dnipropetrovsk Regional Center of Socially Significant Diseases ( Site 5619)

Dnipro, Dnipropetrovsk Oblast, Ukraine

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Regional Clinical Infectious Hospital ( Site 5614)

Kharkiv, Kharkivs’ka Oblast’, Ukraine

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Kherson City Clinical Hospital n.a. Y.Y. Karabelesh ( Site 5620)

Kherson, Kherson Oblast, Ukraine

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Institute of Epidemiology and Infect Diseases of the NAMS of Ukraine ( Site 5615)

Kyiv, Kyivska Oblast, Ukraine

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Mykolaiv center of paliative assistance and integrated services ( Site 5621)

Mykolayiv, Mykolaiv Oblast, Ukraine

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MNE Odesa Regional Center of Socially Significant Diseases ( Site 5611)

Odesa, Odesa Oblast, Ukraine

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MI Vinnytsia Regional Center of AIDS Prevention and Care ( Site 5618)

Berezina, Vinnytsia Oblast, Ukraine

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Kyiv City Clinical Hospital 5 ( Site 5616)

Kyiv, , Ukraine

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Royal Free Hospital ( Site 5202)

London, Camden, United Kingdom

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Western General Hospital ( Site 5201)

Edinburgh, Edinburgh, City of, United Kingdom

Site Status

Countries

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United States Australia Canada Chile Colombia France Germany Italy Japan Peru Portugal Puerto Rico Russia South Africa South Korea Spain Ukraine United Kingdom

References

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Carr A, Mngqibisa R, Khaertynova I, Kumar PN, Haider S, Zhang Y, Correll T, Asante-Appiah E, Greaves W. Efficacy and safety of doravirine/islatravir in heavily treatment-experienced participants living with HIV-1 from a randomized trial. AIDS. 2025 Oct 2. doi: 10.1097/QAD.0000000000004367. Online ahead of print.

Reference Type DERIVED
PMID: 41037024 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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MK-8591A-019

Identifier Type: OTHER

Identifier Source: secondary_id

205243

Identifier Type: REGISTRY

Identifier Source: secondary_id

2019-000588-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8591A-019

Identifier Type: -

Identifier Source: org_study_id