Islatravir (MK-8591) With Doravirine and Lamivudine in Participants Infected With Human Immunodeficiency Virus Type 1 (MK-8591-011)

NCT ID: NCT03272347

Last Updated: 2023-03-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

123 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-27

Study Completion Date

2022-03-09

Brief Summary

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This study will evaluate the safety, tolerability, antiretroviral activity, and pharmacokinetics of 3 doses of islatravir (MK-8591) in combination with doravirine (DOR) and lamivudine (3TC) administered to antiretroviral treatment-naïve adult participants with human immunodeficiency virus type 1 (HIV-1) infection.

Detailed Description

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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
Masking in Part 1, including matching placebo. Masking only to dose in Part 2. No masking in Parts 3 and 4.

Study Groups

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Islatravir 0.25 mg

Participants will be treated once daily (QD) with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.

Group Type EXPERIMENTAL

Islatravir

Intervention Type DRUG

Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered.

Doravirine

Intervention Type DRUG

Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks

Lamivudine

Intervention Type DRUG

Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks

Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate

Intervention Type DRUG

Placebo to doravirine/lamivudine/tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 52 weeks

Doravirine/Islatravir

Intervention Type DRUG

Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks

Islatravir 0.75 mg

Participants will be treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.

Group Type EXPERIMENTAL

Islatravir

Intervention Type DRUG

Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered.

Doravirine

Intervention Type DRUG

Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks

Lamivudine

Intervention Type DRUG

Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks

Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate

Intervention Type DRUG

Placebo to doravirine/lamivudine/tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 52 weeks

Doravirine/Islatravir

Intervention Type DRUG

Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks

Islatravir 2.25 mg

Participants will be treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.

Group Type EXPERIMENTAL

Islatravir

Intervention Type DRUG

Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered.

Doravirine

Intervention Type DRUG

Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks

Lamivudine

Intervention Type DRUG

Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks

Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate

Intervention Type DRUG

Placebo to doravirine/lamivudine/tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 52 weeks

Doravirine/Islatravir

Intervention Type DRUG

Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks

DOR/3TC/TDF

Participants will be treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments may be discontinued and participants will receive only DOR/3TC/TDF QD open label up to Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.

Group Type ACTIVE_COMPARATOR

Placebo to Islatravir

Intervention Type DRUG

Placebo to islatravir is orally administered QD in capsule form for up to 52 weeks

Placebo to Doravirine

Intervention Type DRUG

Placebo to Doravirine is orally administered QD in tablet form for up to 52 weeks

Placebo to Lamivudine

Intervention Type DRUG

Placebo to Lamivudine is orally administered QD in tablet form for up to 52 weeks

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate

Intervention Type DRUG

Fixed dose combination of 100 mg doravirine + 300 mg lamivudine + 300 mg tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 144 weeks.

Doravirine/Islatravir

Intervention Type DRUG

Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks

Interventions

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Islatravir

Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered.

Intervention Type DRUG

Placebo to Islatravir

Placebo to islatravir is orally administered QD in capsule form for up to 52 weeks

Intervention Type DRUG

Doravirine

Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks

Intervention Type DRUG

Placebo to Doravirine

Placebo to Doravirine is orally administered QD in tablet form for up to 52 weeks

Intervention Type DRUG

Lamivudine

Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks

Intervention Type DRUG

Placebo to Lamivudine

Placebo to Lamivudine is orally administered QD in tablet form for up to 52 weeks

Intervention Type DRUG

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate

Fixed dose combination of 100 mg doravirine + 300 mg lamivudine + 300 mg tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 144 weeks.

Intervention Type DRUG

Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate

Placebo to doravirine/lamivudine/tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 52 weeks

Intervention Type DRUG

Doravirine/Islatravir

Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks

Intervention Type DRUG

Other Intervention Names

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MK-8591 MK-1439 3TC MK-1439A MK-8591A

Eligibility Criteria

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Inclusion Criteria

* Has HIV-1 infection
* Is naïve to anti-retroviral therapy (ART).
* Is clinically stable, with no signs or symptoms of acute infection, at the time of entry into the study
* Female is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP); but if WOCBP agrees to follow the contraceptive guidance
* All participants, male and female, agree to use barrier methods of contraception when engaged in any sexual activity during treatment and for 6 weeks following treatment.

Exclusion Criteria

* Is a user of recreational or illicit drugs or has had a history of drug or alcohol abuse or dependence that may interfere with trial participation
* Has significant hypersensitivity or other contraindication to any of the components of the study drugs
* Has a history of malignancy ≤5 years prior
* Female expects to donate eggs at any time during the study
* Is breastfeeding or expecting to conceive
* A WOCBP who has a positive urine pregnancy test on Day 1 before the first dose of study treatment
* Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
* Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study
* Requires any of the following prohibited medications: Carbamazepine, Phenobarbital, Phenytoin, Rifabutin, Rifampin, Herbal remedies, St. John's Wort, Modafinil, Bosentan, Nafcillin, Pentostatin
* Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days of signing informed consent to participate in this current trial
* Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, protease inhibitor, integrase inhibitor
* Has active hepatitis C virus (HCV) coinfection defined as detectable HCV RNA or HBV co-infection defined as hepatitis B surface antigen \[HBsAg\]-positive
* Has a current (active) diagnosis of acute hepatitis due to any cause
* Has previously been randomized in a study and received islatravir (MK-8591), DOR, Doravirine, Tenofovir, Lamivudine, or 3TC.
Minimum Eligible Age

18 Years

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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Pueblo Family Physicians ( Site 0119)

Phoenix, Arizona, United States

Site Status

University California / Davis ( Site 0101)

Sacramento, California, United States

Site Status

Whitman Walker Clinic ( Site 0108)

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

Site Status

Orlando Immunology Center (OIC) ( Site 0105)

Orlando, Florida, United States

Site Status

Northstar Medical Center ( Site 0102)

Chicago, Illinois, United States

Site Status

Kansas City CARE Clinic ( Site 0106)

Kansas City, Missouri, United States

Site Status

Saint Hope Foundation, Inc. ( Site 0116)

Bellaire, Texas, United States

Site Status

North Texas Infectious Diseases Consultants, PA ( Site 0103)

Dallas, Texas, United States

Site Status

Tarrant County Infectious Disease Associates ( Site 0112)

Fort Worth, Texas, United States

Site Status

The Crofoot Research Center, Inc. ( Site 0118)

Houston, Texas, United States

Site Status

Clinica Arauco Salud ( Site 0200)

Santiago, RM, Chile

Site Status

Biomedica Research Group ( Site 0202)

Santiago, , Chile

Site Status

Hospital Dr. Hernan Henriquez Aravena ( Site 0203)

Temuco, , Chile

Site Status

Hopital Avicenne ( Site 2302)

Bobigny, , France

Site Status

Hopital Saint-Andre ( Site 2307)

Bordeaux, , France

Site Status

CHU Hotel Dieu ( Site 2308)

Nantes, , France

Site Status

CHU de Nice Hopital Archet 1 ( Site 2303)

Nice, , France

Site Status

Hopital Bichat - Claude Bernard ( Site 2309)

Paris, , France

Site Status

Hopital Pitie Salpetriere ( Site 2305)

Paris, , France

Site Status

Hopital Saint Louis ( Site 2306)

Paris, , France

Site Status

Centre Hospitalier de Tourcoing ( Site 2301)

Tourcoing, , France

Site Status

Brighton and Sussex University Hospitals NHS Trust ( Site 2105)

Brighton, East Sussex, United Kingdom

Site Status

Chelsea and Westminster Hospital ( Site 2101)

London, , United Kingdom

Site Status

Royal London Hospital ( Site 2103)

London, , United Kingdom

Site Status

The Royal Free London NHS Foundation Trust ( Site 2102)

London, , United Kingdom

Site Status

North Manchester General Hospital ( Site 2104)

Manchester, , United Kingdom

Site Status

Countries

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United States Chile France United Kingdom

References

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Molina JM, Yazdanpanah Y, Afani Saud A, Bettacchi C, Chahin Anania C, Klopfer SO, Grandhi A, Eves K, Hepler D, Robertson MN, Hwang C, Hanna GJ, Correll T. Brief Report: Efficacy and Safety of Oral Islatravir Once Daily in Combination With Doravirine Through 96 Weeks for Treatment-Naive Adults With HIV-1 Infection Receiving Initial Treatment With Islatravir, Doravirine, and Lamivudine. J Acquir Immune Defic Syndr. 2022 Sep 1;91(1):68-72. doi: 10.1097/QAI.0000000000002879. Epub 2021 Dec 8.

Reference Type DERIVED
PMID: 35972855 (View on PubMed)

Molina JM, Yazdanpanah Y, Afani Saud A, Bettacchi C, Chahin Anania C, DeJesus E, Olsen Klopfer S, Grandhi A, Eves K, Robertson MN, Correll T, Hwang C, Hanna GJ, Sklar P. Islatravir in combination with doravirine for treatment-naive adults with HIV-1 infection receiving initial treatment with islatravir, doravirine, and lamivudine: a phase 2b, randomised, double-blind, dose-ranging trial. Lancet HIV. 2021 Jun;8(6):e324-e333. doi: 10.1016/S2352-3018(21)00021-7. Epub 2021 May 14.

Reference Type DERIVED
PMID: 34000227 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2017-000437-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8591-011

Identifier Type: -

Identifier Source: org_study_id

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