A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Antiretroviral Therapy (ART) (MK-8591A-051)

Phase 3Active Not RecruitingNCT05631093

Merck Sharp & Dohme LLC553 enrolled

Overview

The primary objectives of this study are to evaluate the safety and tolerability of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued baseline antiretroviral therapy (ART), through Week 48; and to evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued baseline ART at Week 48. The primary hypothesis is that DOR/ISL is non-inferior to continued baseline ART, as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48, with a margin of 4 percentage points used to define non-inferiority.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

553

Conditions

HIV-1 Infection

Interventions

ART

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Is Human Immunodeficiency Virus-1 (HIV-1) positive with plasma HIV-1 Ribonucleic Acid (RNA) \<50 copies/mL at screening * Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) antiretroviral therapy ART with documented viral suppression (HIV-1 RNA \<50 copies/mL) for ≥3 consecutive months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen * Female is not a participant of childbearing potential (POCBP); or if a POCBP uses an acceptable contraceptive method or abstains from penile-vaginal intercourse as their preferred and usual lifestyle; has a negative highly sensitive pregnancy test; and whose medical history, menstrual history, and recent sexual activity has been reviewed by the investigator Exclusion Criteria: * Has HIV-2 infection * Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator * Has a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening * Has active hepatitis B virus (HBV) infection * Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis * Has a ≤5 years prior history of malignancy * Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers * Has taken long-acting HIV therapy at any time * Is currently participating in or has participated in a clinical study and received (or is receiving) 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 Doravine (DOR)

Locations (53)

Kaiser Permanente-Infectious Disease ( Site 3014)

Los Angeles, California, United States

Palmtree Clinical Research ( Site 3032)

Palm Springs, California, United States

Zuckerberg San Francisco General Hospital and Trauma Center-UCSF ID Clinical Trials Center ( Site 30

San Francisco, California, United States

Georgetown University Medical Center ( Site 3006)

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

Midway Immunology and Research Center ( Site 3009)

Ft. Pierce, Florida, United States

Outcomes

Primary Outcomes

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

HIV-1 RNA levels in plasma were measured by polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.

Time frame: Week 48

Percentage of Participants With One or More Adverse Events (AEs) at Week 48

An AE is defined as 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. The percentage of participants who experienced at least one AE from Day 1 up to Week 48 are reported.

Time frame: Up to Week 48

Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48

Time frame: Up to Week 48

Secondary Outcomes

Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.

Time frame: Week 48

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

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.

Time frame: Week 48

Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.

Time frame: Week 96

Participants With HIV-1 RNA <200 Copies/mL at Week 144

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.

Time frame: Week 144

Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.

Time frame: Week 96

Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 144

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.

Time frame: Week 144

Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.

Time frame: Week 96

Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.

Time frame: Week 144

Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to Week 48

Plasma CD4+ T-Cell Count was measured in cells/mm\^3 for baseline and 48 weeks. Baseline measurements were defined as the Day 1 value of each participant. The mean change of plasma CD4+ T-Cell count from baseline to Week 48 is presented.

Time frame: Baseline at Day 1 and Week 48

Mean Change of Plasma CD4+ T-Cell Count From Baseline Week 48 to Week 96

Mean change from baseline at Week 48 in CD4+ T-cell count at Week 96. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.

Time frame: Baseline at Week 48 and Week 96

Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 48 to Week 144

Mean change from baseline at Week 48 in CD4+ T-cell count at Week 144. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.

Time frame: Baseline at Week 48 and Week 144

Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 96

Mean change from baseline at Day 1 in CD4+ T-cell count at Week 96. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.

Time frame: Baseline at Day 1 and Week 96

Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 144

Mean change from baseline at Day 1 in CD4+ T-cell count at Week 144. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.

Time frame: Baseline at Day 1 and Week 144

Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48

Participants with clinically significant confirmed viremia \[2 consecutive occurences 4 weeks (+-1 week) apart of HIV-1 RNA \>=200 copies/mL at any time during the study\] or who discontinue study intervention for another reason with HIV-1 RNA \>=200 copies/mL at the time of discontinuation met the criteria for post-baseline resistance testing. Participants with HIV-1 RNA \>=400 copies/mL or any participant for whom available genotypic or phenotypic data show evidence of resistance, irrespective of viral load were included in the resistance analysis subset. Plasma samples were collected for genotypic and phenotypic HIV-1 viral drug resistance testing and used to assess resistance-associated substitutions and virus susceptibility to study intervention. The percentage of participants in the resistance analysis subset with treatment-emergent resistance-associated substitutions to the study intervention is presented.

Time frame: Up to Week 48

Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48

Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Low density lipoprotein cholesterol (LDL-C) at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.

Time frame: Baseline and Week 48

Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48

Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Non-HDL-C at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.

Time frame: Baseline and Week 48

Participants With One or More AEs at Week 96

Time frame: Up to Week 96

Participants With One or More AEs at Week 144

Time frame: Up to Week 144

Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 96

Time frame: Up to Week 96

Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 144

Time frame: Up to Week 144

Percentage of Participants With One or More AEs From Week 48 up to Week 96

Time frame: Week 48 up to Week 96

Percentage of Participants With One or More AEs From Week 48 up to Week 144

Time frame: Week 48 up to Week 144

Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 96

Time frame: Week 48 up to Week 96

Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 144

Time frame: Week 48 up to Week 144