MK-8527 Single-Dose Trial in HIV-1 Infected Participants (MK-8527-004)

A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8527 Monotherapy in Anti-Retroviral Therapy (ART)-Naïve, HIV-1 Infected Participants

This is a single-dose clinical study to evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral activity of MK-8527 in antiretroviral therapy (ART)-naïve participants living with human immunodeficiency virus type 1 (HIV-1) infection. The primary hypothesis is that, at a dose that is safe and generally well tolerated, MK-8527 will have antiretroviral activity as measured by a reduction from baseline in plasma HIV-1 ribonucleic acid (RNA) of ≥1.0 log10 copies/mL. A total of 4 arms was initially planned but Arm D was never initiated as the primary objectives were achieved following completion of Arms A to C.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus
• Intervention / Treatment: Drug: MK-8527

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Romania
  • Bucuresti
    • București, Bucuresti, Romania
      • ARENSIA Exploratory Medicine-Institutul National de Boli Infectioase Matei Bals ( Site 0004)
• South Africa
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Josha Research ( Site 0003)
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2092
      • Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0002)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • Desmond Tutu Health Foundation ( Site 0001)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is in good health other than HIV-1 infection
• Is documented HIV-1 positive
• Is ART-naïve, which is defined as not having received any marketed antiretroviral agent for treatment of HIV-1 infection (prior use of an ART for PrEP or investigational therapy is permitted if the last dose was ≥30 days prior to study drug administration)
• Is willing to receive no other ART for the monitoring period of this study

Exclusion Criteria:

• Has a history of clinically significant endocrine, GI, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
• Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study intervention, throughout the study, until the poststudy visit
• Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A: MK-8527 1.0 mg; Participants receive a single oral dose of MK-8527 1.0 mg.	Drug: MK-8527; MK-8527 capsule taken by mouth.
Experimental: Panel B: MK-8527 0.5 mg; Participants receive a single oral dose of MK-8527 0.5 mg.	Drug: MK-8527; MK-8527 capsule taken by mouth.
Experimental: Panel C: MK-8527 0.25 mg; Participants receive a single oral dose of MK-8527 0.25 mg.	Drug: MK-8527; MK-8527 capsule taken by mouth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)	The mean change from baseline in HIV-1 RNA counts at 168 hours after a single doses of MK-8527 is reported.	Baseline and 168 hours postdose on Day 1
Number of Participants Experiencing ≥1 Adverse Event (AE)	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 28 days
Number of Participants Discontinuing From Study Due to an AE	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 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve From Predose to 168 Hours Postdose (AUC0-168) of MK-8527 Triphosphate (MK-8527-TP) in Peripheral Blood Mononuclear Cells (PBMCs)	The AUC0-168 of MK-8527-TP in PBMCs is reported.	Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose
Area Under the Concentration-Time Curve From Predose to Infinity (AUC0-inf) of MK-8527-TP in PBMCs	The MK-8527-TP AUC0-inf in PBMCs is reported.	Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose
Area Under the Concentration-Time Curve From Predose to Last Measurable Concentration (AUC0-last) of MK-8527-TP in PBMCs	The MK-8527-TP AUC0-last in PBMCs is reported.	Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose
Maximum Concentration (Cmax) of MK-8527-TP in PBMCs	The MK-8527-TP Cmax in PBMCs is reported.	Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose
Concentration at 168 Hours Postdose (C168) of MK-8527-TP in PBMCs	The C168 of MK-8527-TP in PBMCs is reported.	168 hours postdose
Time to Maximum Concentration (Tmax) of MK-8527-TP in PBMCs	The MK-8527-TP Tmax in PBMCs is reported.	Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose
Apparent Terminal Half-life (t½) of MK-8527-TP in PBMCs	The apparent t½ of MK-8527-TP in PBMCs is reported.	Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose
AUC0-inf of MK-8527 in Plasma	The AUC0-inf of MK-8527 in plasma is reported.	Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
AUC0-last of MK-8527 in Plasma	The AUC0-last of MK-8527 in plasma is reported.	Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
Clast of MK-8527 in Plasma	The Clast of MK-8527 in plasma is reported.	Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
Cmax of MK-8527 in Plasma	The Cmax of MK-8527 in plasma is reported.	Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
Tmax of MK-8527 in Plasma	The Tmax of MK-8527 in plasma is reported.	Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
Apparent t½ of MK-8527 in Plasma	The apparent t½ of MK-8527 in plasma is reported.	Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
Correlation Between Intracellular C168 of MK-8527-TP in PBMCs and Change From Baseline in Plasma HIV-1 RNA	The correlation between between the C168 of MK-8527-TP in PBMCs and the change from baseline in plasma HIV-1 RNA levels 168 hours after dosing was calculated based on all pooled participants. All participants who complied with the protocol sufficiently to ensure that generated data will belikely to exhibit the effects of treatment, according to the underlying scientific model, are included. Participants with data below the LLOQ are excluded.	Predose and 168 hours postdose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2022
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: August 8, 2022
• First Posted (Actual): August 10, 2022

Study Record Updates

• Last Update Posted (Actual): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: 8527-004; MK-8527-004 (Other Identifier: Merck); 2023-503682-39 (Registry Identifier: EU CT); U1111-1287-7295 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes