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

Phase 3

Active, not recruiting

• Conditions: HIV-1 Infection
• Interventions: Drug: DOR/ISL; Drug: BIC/FTC/TAF; Drug: Placebo to BIC/FTC/TAF; Drug: Placebo to DOR/ISL

• Registration Number: NCT05705349
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-20
• Study First Submitted QC: 2023-01-20
• Study First Posted: 2023-01-30
• Study Start: 2023-03-08
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-18
• Last Update Posted: 2024-10-21
• Primary Completion: 2025-10-19
• Study Completion: 2029-08-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 500

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DOR/ISL	DOR/ISL	Participants take DOR/ISL and placebo to BIC/FTC/TAF once daily (qd) for 144 weeks.
DOR/ISL	Placebo to BIC/FTC/TAF	Participants take DOR/ISL and placebo to BIC/FTC/TAF once daily (qd) for 144 weeks.
BIC/FTC/TAF	BIC/FTC/TAF	Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 144 weeks.
BIC/FTC/TAF	Placebo to DOR/ISL	Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 144 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL at Week 48	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	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	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 Outcome Measures

Name	Time	Method
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96	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.
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144	Week 144	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.
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48	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.
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96	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.
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144	Week 144	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.
Change from baseline in cluster of differentiation 4+ (CD4+) T-cells at Week 48	Baseline (Day 1) and Week 48	CD4+ T-cells are quantified with a T and B lymphocyte and natural killer cell (TBNK) panel.
Change from baseline in CD4+ T-cells at Week 144	Baseline (Day 1) and Week 144	CD4+ T-cells are quantified with a TBNK panel.
Incidence of viral drug resistance	Up to 96 weeks	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.
Change from baseline in body weight at Week 48	Baseline (Day 1) and Week 48	Body weight will be collected throughout the study.
Change from baseline in body weight at Week 96	Baseline (Day 1) and Week 96	Body weight will be collected throughout the study.
Change from baseline in body weight at Week 144	Baseline (Day 1) and Week 144	Body weight will be collected throughout the study.
Percentage of participants experiencing ≥1 AE through Week 144	Up to 144 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 144	Up to 144 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.
Change from baseline in CD4+ T-cells at Week 96	Baseline (Day 1) and Week 96	CD4+ T-cells are quantified with a TBNK panel.

Trial Locations

Locations (131)

Pueblo Family Physicians ( Site 5674); 🇺🇸 Phoenix, Arizona, United States

Pacific Oaks Medical Group ( Site 5681); 🇺🇸 Beverly Hills, California, United States

Ruane Clinical Research Group, Inc ( Site 5658); 🇺🇸 Los Angeles, California, United States

Vivent Health ( Site 5694); 🇺🇸 Denver, Colorado, United States

Washington Health Institute ( Site 5689); 🇺🇸 Washington, District of Columbia, United States

Midway Immunology and Research Center ( Site 5657); 🇺🇸 Fort Pierce, Florida, United States

AHF South Beach ( Site 5663); 🇺🇸 Miami Beach, Florida, United States

AHF The Kinder Medical Group ( Site 5672); 🇺🇸 Miami, Florida, United States

Orlando Immunology Center ( Site 5654); 🇺🇸 Orlando, Florida, United States

CAN Community Health - Sarasota ( Site 5668); 🇺🇸 Sarasota, Florida, United States

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