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

Merck Sharp & Dohme LLC123 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

123

Conditions

HIV-1 Infection

Interventions

IslatravirDRUG

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.

Placebo to IslatravirDRUG

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

DoravirineDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (26)

Outcomes

Primary Outcomes

Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24

Blood samples were collected and plasma human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) were quantified using a real time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.

Time frame: Week 24

Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48

Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.

Time frame: Week 48

Number of Participants Experiencing Adverse Events (AEs) up to Week 144

An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment.

Time frame: Up to 144 weeks

Number of Participants Discontinuing Study Drug Due to AEs up to Week 144

An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment.

Time frame: Up to 144 weeks

Secondary Outcomes

Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen

Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.

Data from ClinicalTrials.gov

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

LamivudineDRUG

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

Placebo to LamivudineDRUG

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

Doravirine/Lamivudine/Tenofovir Disoproxil FumarateDRUG

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.

Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil FumarateDRUG

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

Doravirine/IslatravirDRUG

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

Pueblo Family Physicians ( Site 0119)

Phoenix, Arizona, United States

University California / Davis ( Site 0101)

Sacramento, California, United States

Whitman Walker Clinic ( Site 0108)

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

Orlando Immunology Center (OIC) ( Site 0105)

Orlando, Florida, United States

Northstar Medical Center ( Site 0102)

Chicago, Illinois, United States

Kansas City CARE Clinic ( Site 0106)

Kansas City, Missouri, United States

Saint Hope Foundation, Inc. ( Site 0116)

Bellaire, Texas, United States

North Texas Infectious Diseases Consultants, PA ( Site 0103)

Dallas, Texas, United States

Tarrant County Infectious Disease Associates ( Site 0112)

Fort Worth, Texas, United States

The Crofoot Research Center, Inc. ( Site 0118)

Houston, Texas, United States

...and 16 more locations

Time frame: Up to 24 weeks after 3TC and Placebo are discontinued from the regimen (up to approximately 60 weeks after initiating treatment)

Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen

Time frame: Up to 48 weeks

Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen (Part 4)

Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure. The percentage of participants with HIV-1 RNA \<50 copies in Part 4 are reported.

Time frame: Up to Week 192

Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24

Blood samples were collected and cluster of differentiation (CD4)+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.

Time frame: Baseline and Week 24

Change From Baseline in CD4+ T-cell Count at Week 48

Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.

Time frame: Baseline and Week 48

Change From Baseline in CD4+ T-cell Count at Week 96

Time frame: Baseline and Week 96

Change From Baseline in CD4+ T-cell Count at Week 144

Time frame: Baseline and Week 144

Change From Baseline in CD4+ T-cell Count at Week 192 (Part 4)

Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Week 144 value. The change from baseline in CD4+ T-cell count at Week 192 (Part 4) are reported.

Time frame: Baseline and Week 192

Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen

Time frame: Up to 24 weeks

Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen

Time frame: Up to 24 weeks

Number of Participants Experiencing AEs From Week 96 Through Study Duration

Time frame: Week 96 up to Week 192

Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration

Time frame: Week 96 up to Week 192

Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)

Time frame: Week 144 up to Week 192

Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)

Time frame: Week 144 up to Week 192