DOR/ISL in HIV-1 Antiretroviral Treatment-naïve Participants (MK-8591A-053)

Study Overview
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Brief Summary
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This is a randomized, active-controlled, double-blind clinical study designed to evaluate the antiretroviral activity, safety, and tolerability of doravirine/islatravir (DOR/ISL [MK-8591A]) in treatment-naïve participants with human immunodeficiency virus type 1 (HIV-1) infection. It is hypothesized that DOR/ISL is non-inferior to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as assessed by the percentage of participants with HIV-1 ribonucleic acid (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 the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in HIV-1 Infected Treatment-Naïve Participants

Conditions
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HIV-1 Infection

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is HIV-1 positive with plasma HIV-1 RNA ≥500 copies/mL at screening Is naïve to antiretroviral therapy (ART) defined as having received no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection If female, is not a participant of childbearing potential (POCBP); or if a POCBP, is 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 hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator Has a diagnosis of an active AIDS-defining opportunistic infection within 30 days prior to screening Has active hepatitis B infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA]-positive). Has chronic hepatitis C virus (HCV) infection (detectable HCV ribonucleic acid [RNA]) and lab values are 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 Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality, or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate

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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Accepts Healthy Volunteers

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<br>Participants take DOR/ISL and placebo to BIC/FTC/TAF once daily (qd) for 96 weeks. | Drug: DOR/ISL<br>* Fixed dose combination tablet containing DOR/ISL 100 mg/0.25 mg taken by mouth.<br>* Other names: MK-8591A;Drug: Placebo to BIC/FTC/TAF<br>* Placebo tablet matched to BIC/FTC/TAF tablet taken by mouth.<br>|
| Active Comparator: BIC/FTC/TAF<br>Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 96 weeks. | Drug: BIC/FTC/TAF<br>* Fixed dose combination tablet containing BIC/FTC/TAF 50 mg/200 mg/25 mg taken by mouth.<br>Drug: Placebo to DOR/ISL<br>* Placebo tablet matched to DOR/ISL tablet taken by mouth.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL at Week 48 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a polymerase chain reaction (PCR) assay with a lower limit of detection of <50 copies/mL. | Week 48 | 
| Percentage of participants experiencing ≥1 adverse event (AE) 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 48 weeks | 
| Percentage of participants discontinuing from study treatment due to an AE 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 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of <50 copies/mL. | Week 96 | 
| Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of <50 copies/mL. | Week 48 | 
| Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of <50 copies/mL. | Week 96 | 
| Change from baseline in cluster of differentiation 4+ (CD4+) T-cells at Week 48 | CD4+ T-cells are quantified with a T and B lymphocyte and natural killer cell (TBNK) panel. | Baseline (Day 1) and Week 48 | 
| Change from baseline in CD4+ T-cells at Week 96 | CD4+ T-cells are quantified with a TBNK panel. | Baseline (Day 1) and Week 96 | 
| Incidence of viral drug resistance | Plasma samples will be collected for genotypic and phenotypic HIV-1 viral drug resistance testing and used to assess resistance-associated substitutions and viral susceptibility as applicable during the study. | Up to 96 weeks | 
| Change from baseline in body weight at Week 48 | Body weight will be collected throughout the study. | Baseline (Day 1) and Week 48 | 
| Change from baseline in body weight at Week 96 | Body weight will be collected throughout the study. | Baseline (Day 1) and Week 96 | 
| Percentage of participants experiencing ≥1 AE through Week 96 | 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 96 weeks | 
| Percentage of participants discontinuing from study treatment due to an AE through Week 96 | 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 96 weeks |