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)

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued 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.

Official Title
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A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: DOR/ISL
* Drug: BIC/FTC/TAF
* Drug: Placebo to BIC/FTC/TAF
* Drug: Placebo to DOR/ISL


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DOR/ISL and Placebo to BIC/FTC/TAF<br>Participants will receive DOR/ISL 100 mg/0.25 mg and Placebo to BIC/FTC/TAF once daily (QD) orally from day 1 to week 96. | Drug: DOR/ISL<br>* DOR/ISL 100 mg/0.25 mg oral tablets once daily<br>* Other names: MK-8591A;Drug: Placebo to BIC/FTC/TAF<br>* 0 mg oral tablets once daily<br>|
| Active Comparator: BIC/FTC/TAF and Placebo to DOR/ISL<br>Participants will receive BIC/FTC/TAF 50 mg/200 mg/25 mg and Placebo to DOR/ISL once daily (QD) orally from day 1 to week 96. | Drug: BIC/FTC/TAF<br>* BIC/FTC/TAF 50 mg/200 mg/25 mg oral tablets once daily<br>Drug: Placebo to DOR/ISL<br>* 0 mg oral tablets once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 | Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 will be reported. | Week 48 | 
| Percentage of participants who experience adverse events (AEs) through Week 48 | 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. | Up to Week 48 | 
| Percentage of participants who discontinue study intervention due to AEs through Week 48 | 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. | Up to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 96 | 
| Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 | Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 will be reported. | Week 48 | 
| Percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 | Percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 will be reported. | Week 48 | 
| 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. | 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. | Week 96 | 
| Change from baseline in CD4+ T-cell count at Week 48 | Mean change from baseline at Day 1 in CD4+ T-cell count at Week 48 will be reported. | Baseline at Day 1 and Week 48 | 
| 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. | Baseline at Day 1 and Week 96 | 
| Number of participants with viral drug resistance mutations at Week 48 | Number of participants with evidence of viral drug resistance-associated substitutions at Week 48 will be reported. | Week 48 | 
| 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. | Week 96 | 
| Percentage of participants who experience AEs through study duration | 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. | Up to Week 102 | 
| Percentage of participants who discontinue study intervention due to AEs through study duration | 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. | Up to Week 96 |