Clinical trial NCT03272347: Islatravir (MK-8591) With Doravirine and Lamivudine in Participants Infected With Human Immunodeficiency Virus Type 1 (MK-8591-011)
Official title: A Phase 2B, Randomized, Double-Blind, Active-Comparator-Controlled, Dose-Ranging Clinical Trial to Evaluate the Safety, Tolerability, Antiretroviral Activity, and Pharmacokinetics of MK-8591 Given in Combination With Doravirine (DOR) and Lamivudine (3TC) in HIV-1-Infected Treatment-Naïve Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-09-05
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24
timeFrame: Week 24
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
timeFrame: Week 48
measure: Number of Participants Experiencing Adverse Events (AEs) up to Week 144
timeFrame: Up to 144 weeks
measure: Number of Participants Discontinuing Study Drug Due to AEs up to Week 144
timeFrame: Up to 144 weeks
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
timeFrame: Up to 24 weeks after 3TC and Placebo are discontinued from the regimen (up to approximately 60 weeks after initiating treatment)
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen
timeFrame: Up to 48 weeks
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen (Part 4)
timeFrame: Up to Week 192
measure: Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in CD4+ T-cell Count at Week 48
timeFrame: Baseline and Week 48
measure: Change From Baseline in CD4+ T-cell Count at Week 96
timeFrame: Baseline and Week 96
measure: Change From Baseline in CD4+ T-cell Count at Week 144
timeFrame: Baseline and Week 144
measure: Change From Baseline in CD4+ T-cell Count at Week 192 (Part 4)
timeFrame: Baseline and Week 192
measure: Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
timeFrame: Up to 24 weeks
measure: Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
timeFrame: Up to 24 weeks
measure: Number of Participants Experiencing AEs From Week 96 Through Study Duration
timeFrame: Week 96 up to Week 192
measure: Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration
timeFrame: Week 96 up to Week 192
measure: Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
timeFrame: Week 144 up to Week 192
measure: Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
timeFrame: Week 144 up to Week 192
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pueblo Family Physicians ( Site 0119)
state: Arizona
city: Sacramento
country: United States
facility: University California / Davis ( Site 0101)
state: California
city: Washington
country: United States
facility: Whitman Walker Clinic ( Site 0108)
state: District of Columbia
city: Orlando
country: United States
facility: Orlando Immunology Center (OIC) ( Site 0105)
state: Florida
city: Chicago
country: United States
facility: Northstar Medical Center ( Site 0102)
state: Illinois
city: Kansas City
country: United States
facility: Kansas City CARE Clinic ( Site 0106)
state: Missouri
city: Bellaire
country: United States
facility: Saint Hope Foundation, Inc. ( Site 0116)
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, PA ( Site 0103)
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Disease Associates ( Site 0112)
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center, Inc. ( Site 0118)
state: Texas
city: Santiago
country: Chile
facility: Clinica Arauco Salud ( Site 0200)
state: RM
city: Santiago
country: Chile
facility: Biomedica Research Group ( Site 0202)
city: Temuco
country: Chile
facility: Hospital Dr. Hernan Henriquez Aravena ( Site 0203)
city: Bobigny
country: France
facility: Hopital Avicenne ( Site 2302)
city: Bordeaux
country: France
facility: Hopital Saint-Andre ( Site 2307)
city: Nantes
country: France
facility: CHU Hotel Dieu ( Site 2308)
city: Nice
country: France
facility: CHU de Nice Hopital Archet 1 ( Site 2303)
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard ( Site 2309)
city: Paris
country: France
facility: Hopital Pitie Salpetriere ( Site 2305)
city: Paris
country: France
facility: Hopital Saint Louis ( Site 2306)
city: Tourcoing
country: France
facility: Centre Hospitalier de Tourcoing ( Site 2301)
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust ( Site 2105)
state: East Sussex
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital ( Site 2101)
city: London
country: United Kingdom
facility: Royal London Hospital ( Site 2103)
city: London
country: United Kingdom
facility: The Royal Free London NHS Foundation Trust ( Site 2102)
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital ( Site 2104)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.