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
Overview
- Phase
- Phase 3
- Intervention
- DOR/ISL
- Conditions
- HIV-1 Infection
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 537
- Locations
- 131
- Primary Endpoint
- Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL at Week 48
- Status
- Active, not recruiting
- Last Updated
- 6 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
DOR/ISL
Participants take DOR/ISL and placebo to BIC/FTC/TAF once daily (qd) for 144 weeks.
Intervention: DOR/ISL
DOR/ISL
Participants take DOR/ISL and placebo to BIC/FTC/TAF once daily (qd) for 144 weeks.
Intervention: Placebo to BIC/FTC/TAF
BIC/FTC/TAF
Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 144 weeks.
Intervention: BIC/FTC/TAF
BIC/FTC/TAF
Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 144 weeks.
Intervention: Placebo to DOR/ISL
Outcomes
Primary Outcomes
Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL at Week 48
Time Frame: 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.
Percentage of participants experiencing ≥1 adverse event (AE) through Week 48
Time Frame: Up to 48 weeks
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.
Percentage of participants discontinuing from study treatment due to an AE through Week 48
Time Frame: Up to 48 weeks
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.
Secondary Outcomes
- Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144(Week 144)
- Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48(Week 48)
- Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96(Week 96)
- Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96(Week 96)
- Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144(Week 144)
- Change from baseline in cluster of differentiation 4+ (CD4+) T-cells at Week 48(Baseline (Day 1) and Week 48)
- Change from baseline in CD4+ T-cells at Week 96(Baseline (Day 1) and Week 96)
- Change from baseline in CD4+ T-cells at Week 144(Baseline (Day 1) and Week 144)
- Incidence of viral drug resistance(Up to 96 weeks)
- Change from baseline in body weight at Week 48(Baseline (Day 1) and Week 48)
- Change from baseline in body weight at Week 96(Baseline (Day 1) and Week 96)
- Change from baseline in body weight at Week 144(Baseline (Day 1) and Week 144)
- Percentage of participants experiencing ≥1 AE through Week 144(Up to 144 weeks)
- Percentage of participants discontinuing from study treatment due to an AE through Week 144(Up to 144 weeks)