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Phase 3 N=599 Randomized Double-blind Treatment

Study of Doravirine/Islatravir (DOR/ISL 100 mg/0.75 mg) to Evaluate the Antiretroviral Activity, Safety, and Tolerability in Treatment-Naïve Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-020)

HIV-1 Infection

Enrolled (actual)
599
Serious AEs
4.1%
Results posted
Nov 2023
Primary outcome: Primary: Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 — 88.9; 88.3 Percentage of participants

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
DOR/ISL (Drug); BIC/FTC/TAF (Drug); Placebo to BIC/FTC/TAF (Drug); Placebo to DOR/ISL (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Merck Sharp & Dohme LLC
Primary completion
Nov 2022

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
88.9; 88.3
PRIMARY
Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48
90.6; 86.3
PRIMARY
Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48
7.4; 3.3
SECONDARY
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
51.7; 57.9 0.945
SECONDARY
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144
64.1; 82.9
SECONDARY
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48
88.6; 86.3
SECONDARY
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48
89.6; 88.6
SECONDARY
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96
51.0; 57.5
SECONDARY
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96
52.3; 58.5
SECONDARY
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144
64.1; 82.9
SECONDARY
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144
64.1; 82.9
SECONDARY
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48
182.4; 233.5
SECONDARY
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 96
217.05; 319.92
SECONDARY
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 144
239.6; 350.9
SECONDARY
Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48
1; 0
SECONDARY
Incidence of Viral RASs at Week 96
2; 0
SECONDARY
Incidence of Viral RASs at Week 144
2; 0
SECONDARY
Mean Change From Baseline in Body Weight at Week 48
3.45; 3.32 0.73
SECONDARY
Mean Change From Baseline in Body Weight at Week 96
3.31; 4.13 0.268
SECONDARY
Mean Change From Baseline in Body Weight at Week 144
4.55; 3.55
SECONDARY
Percentage of Participants Who Experienced an Adverse Event (AE)
96.6; 94.0
SECONDARY
Percentage of Participants Who Discontinued Study Treatment Due to an AE
14.1; 9.0

Summary

This is a phase 3, randomized, controlled, double-blind, multisite clinical study of a once-daily fixed dose combination (FDC) of 100 mg doravirine/0.75 mg islatravir (DOR/ISL [also known as MK-8591A]) in treatment-naïve participants living with human immunodeficiency virus type-1 (HIV-1) infection. The primary objectives are to evaluate the antiretroviral activity, safety, and tolerability of DOR/ISL compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that DOR/ISL is noninferior or superior to BIC/FTC/TAF treatment based on the percentage of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48.

Eligibility Criteria

Inclusion Criteria

  • Is human immunodeficiency virus type 1 (HIV-1) positive
  • Is naïve to antiretroviral therapy (ART) defined as having received ≤10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection including prevention of mother-to-child transmission up to 1 month prior to screening.
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); 2) Is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis); 3) A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention; 4) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required

Exclusion Criteria

  • Has human immunodeficiency virus type 2 (HIV-2) infection
  • Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
  • Has an active diagnosis of hepatitis due to any cause, including active hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen [HBsAg]-positive or hepatitis B virus deoxyribonucleic acid [HBV DNA]-positive)
  • Has a history of malignancy ≤5 years prior to signing 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
  • Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
  • Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapy from 45 days prior to Day 1 through the study intervention period
  • Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study intervention period
  • Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, or any study intervention
  • Has exclusionary laboratory values within 45 days prior to Day 1
  • Is female and is expecting to conceive or donate eggs at any time during the study
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04233879). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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