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

• ClinicalTrials.gov Identifier: NCT05705349
• Recruitment Status: Recruiting
• First Posted: January 30, 2023
• Last Update Posted: May 16, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: January 20, 2023
• First Posted Date: January 30, 2023
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: March 8, 2023
• Estimated Primary Completion Date: October 19, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 14, 2023)

• 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.

Original Primary Outcome Measures (submitted: January 20, 2023)

• 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.

Current Secondary Outcome Measures (submitted: January 20, 2023)

• Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 [ Time Frame: 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 48 [ Time Frame: 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 [ Time Frame: 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.
• Change from baseline in cluster of differentiation 4+ (CD4+) T-cells at Week 48 [ Time Frame: 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 96 [ Time Frame: Baseline (Day 1) and Week 96 ]
  CD4+ T-cells are quantified with a TBNK panel.
• Incidence of viral drug resistance [ Time Frame: 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 [ Time Frame: Baseline (Day 1) and Week 48 ]
  Body weight will be collected throughout the study.
• Change from baseline in body weight at Week 96 [ Time Frame: Baseline (Day 1) and Week 96 ]
  Body weight will be collected throughout the study.
• Percentage of participants experiencing ≥1 AE through Week 96 [ Time Frame: Up to 96 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 96 [ Time Frame: Up to 96 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: DOR/ISL in HIV-1 Antiretroviral Treatment-naïve Participants (MK-8591A-053)
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: HIV-1 Infection

Intervention

• Drug: DOR/ISL
  Fixed dose combination tablet containing DOR/ISL 100 mg/0.25 mg taken by mouth.
  Other Name: MK-8591A
• Drug: BIC/FTC/TAF
  Fixed dose combination tablet containing BIC/FTC/TAF 50 mg/200 mg/25 mg taken by mouth.
• Drug: Placebo to DOR/ISL
  Placebo tablet matched to DOR/ISL tablet taken by mouth.
• Drug: Placebo to BIC/FTC/TAF
  Placebo tablet matched to BIC/FTC/TAF tablet taken by mouth.

Study Arms

• Experimental: DOR/ISL
  Participants take DOR/ISL and placebo to BIC/FTC/TAF once daily (qd) for 96 weeks.
  Interventions:

  • Drug: DOR/ISL
  • Drug: Placebo to BIC/FTC/TAF
• Active Comparator: BIC/FTC/TAF
  Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 96 weeks.
  Interventions:

  • Drug: BIC/FTC/TAF
  • Drug: Placebo to DOR/ISL

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 20, 2023): 500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 1, 2026
• Estimated Primary Completion Date: October 19, 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

• Listed Location Countries: Argentina, Chile, Colombia, France, Germany, Guatemala, Israel, Japan, Malaysia, Puerto Rico, South Africa, Spain, Switzerland, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT05705349
• Other Study ID Numbers: 8591A-053; 2022-502099-22-00 ( Other Identifier: EU CT ); jRCT2031220720 ( Registry Identifier: jRCT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: May 2024