A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-052)

Phase 3Active Not RecruitingNCT05630755

Merck Sharp & Dohme LLC514 enrolled

Overview

The primary objectives of this study are to evaluate the antiretroviral activity of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) at Week 48; and to evaluate the safety and tolerability of a switch to DOR/ISL compared with continued BIC/FTC/TAF, through Week 48. The primary hypotheses are that (1) DOR/ISL is non-inferior to continued BIC/FTC/TAF, 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; and (2) DOR/ISL is superior to BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

514

Conditions

HIV-1 Infection

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

The key inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: * Is HIV-1 positive with plasma HIV-1 RNA \<50 copies/mL * Has been receiving BIC/FTC/TAF therapy 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 participant of childbearing potential, not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration Exclusion Criteria: * Has HIV-2 infection * 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 with laboratory values consistent with cirrhosis * Has a history of malignancy ≤5 years prior to providing documented informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma * Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers * Has a documented or known virologic resistance to DOR * Has taken long-acting HIV therapy at any time (e.g., cabotegravir, lenacapavir) * 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 except those currently enrolled in the comparator arm of an ongoing DOR/ISL study

Locations (49)

Pueblo Family Physicians ( Site 1425)

Phoenix, Arizona, United States

Pacific Oaks Medical Group ( Site 1400)

Beverly Hills, California, United States

Ruane Clinical Research Group, Inc ( Site 1414)

Los Angeles, California, United States

Mills Clinical Research ( Site 1433)

Los Angeles, California, United States

Whitman-Walker Institute ( Site 1431)

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

Outcomes

Primary Outcomes

Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥50 Copies/mL at Week 48

HIV-1 RNA levels in blood samples taken at each visit were measured 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 Who Experience Adverse Events (AEs) Through Week 48

An AE was 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 is reported.

Time frame: Up to Week 48

Percentage of Participants Who Discontinue Study Intervention Due to AEs Through 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 blood samples taken at each visit were measured 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 blood samples taken at each visit were measured 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

Change From Baseline in Cluster of Differentiation 4-positive (CD4+) T-cell Count at 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 change from baseline to Week 48 and corresponding 2-sided 95% confidence intervals were calculated based on cLDA models adjusted by treatment group, time, and the interaction of time-by-treatment group.

Time frame: Baseline at Day 1 and Week 48

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. Per protocol, 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

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

Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 will be reported.

Time frame: Week 96

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

Percentage of participants with HIV-1 RNA \<200 copies/mL at Week 96 will be reported.

Time frame: Week 96

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

Percentage of participants with HIV-1 RNA \<50 copies/mL at Week 96 will be reported.

Time frame: Week 96

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

Mean change from baseline at Day 1 in CD4+ T-cell count at Week 96 will be reported.

Time frame: Baseline at Day 1 and Week 96

Number of Participants With Viral Drug Resistance Mutations at Week 96

Number of participants with evidence of viral drug resistance-associated substitutions at Week 96 will be reported.

Time frame: Week 96

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

Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 will be reported.

Time frame: Week 144

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

Percentage of participants with HIV-1 RNA \<200 copies/mL at Week 144 will be reported.

Time frame: Week 144

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

Percentage of participants with HIV-1 RNA \<50 copies/mL at Week 144 will be reported.

Time frame: Week 144

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

Mean change from baseline at Day 1 in CD4+ T-cell count at Week 144 will be reported.

Time frame: Baseline at Day 1 and Week 144

Number of Participants With Viral Drug Resistance Mutations at Week 144

Number of participants with evidence of viral drug resistance-associated substitutions at Week 144 will be reported.

Time frame: Week 144

Percentage of Participants Who Experience AEs Through Week 144

An AE is 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.

Time frame: Up to Week 144

Percentage of Participants Who Discontinue Study Intervention Due to AEs Through Week 144

An AE is 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.

Time frame: Up to Week 144