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)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Randomized, Active-Controlled, Open-Label 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 Antiretroviral Therapy

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: ART
* Drug: DOR/ISL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL at screening Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) 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 DOR

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ART + DOR/ISL<br>Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months on a stable oral ART are first treated with standard of care (SOC) ART for 48 weeks, followed by 48 weeks of treatment with DOR/ISL | Drug: ART<br>* Standard of care ART, per approved product list, taken orally<br>Drug: DOR/ISL<br>* Combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.<br>* Other names: MK-8591A;|
| Experimental: DOR/ISL<br>Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months on a stable oral ART are treated with DOR/ISL for 96 weeks | Drug: DOR/ISL<br>* Combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.<br>* Other names: MK-8591A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with HIV-1 RNA ≥50 copies/mL at Week 48 | Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 | Week 48 | 
| Participants with one or more AEs at Week 48 | Percentage of participants with one or more AEs from Day 1 up to Week 48 | Up to Week 48 | 
| Participants with an AE leading to discontinuation of study intervention at Week 48 | Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 48 | Up to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with HIV-1 RNA <200 copies/mL at Week 48 | Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 | Week 48 | 
| Participants with HIV-1 RNA <50 copies/mL at Week 48 | Percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 | Week 48 | 
| Participants with HIV-1 RNA <200 copies/mL at Week 96 | Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 | Week 96 | 
| Participants with HIV-1 RNA ≥50 copies/mL at Week 96 | Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 | Week 96 | 
| Participants with HIV-1 RNA <50 copies/mL at Week 96 | Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 | Week 96 | 
| Change from Day 1 in cluster of differentiation 4+ (CD4+) T-cell count at Week 48 | Mean change from baseline at Day 1 in CD4+ T-cell count at Week 48 | Baseline at Day 1 and Week 48 | 
| Change from Week 48 in CD4+ T-cell count at 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. | Baseline at Week 48 and Week 96 | 
| Change from Day 1 in CD4+ T-cell count at 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. | Baseline at Day 1 and Week 96 | 
| Participants with viral resistance-associated substitutions | Number of participants with viral resistance-associated substitutions | Up to Week 96 | 
| Low density lipoprotein cholesterol (LDL-C) | Mean change from Baseline to Week 48 in fasting LDL-C | Baseline and Week 48 | 
| High density lipoprotein cholesterol (HDL-C) | Mean change from baseline to Week 48 in fasting HDL-C | Baseline and Week 48 | 
| Participants with one or more AEs at Week 96 | Percentage of participants with one or more AEs from Day 1 up to Week 96 | Up to Week 96 | 
| Participants with AEs leading to discontinuation of study intervention at Week 96 | Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 96 | Up to Week 96 | 
| Participants with one or more AEs from Week 48 up to Week 96 | Percentage of participants with one or more AEs from Week 48 up to Week 96 | Week 48 up to Week 96 | 
| Participants with AEs leading to discontinuation of study intervention from Week 48 up to Week 96 | Percentage of participants with an AE leading to discontinuation of study intervention from Week 48 up to Week 96 | Week 48 up to Week 96 |