Clinical trial NCT05494736: MK-8527 Single-Dose Trial in HIV-1 Infected Participants (MK-8527-004)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Human Immunodeficiency Virus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-08-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)
timeFrame: Baseline and 168 hours postdose on Day 1
measure: Number of Participants Experiencing ≥1 Adverse Event (AE)
timeFrame: Up to 28 days
measure: Number of Participants Discontinuing From Study Due to an AE
timeFrame: Up to 28 days
Secondary outcomes:
measure: 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)
timeFrame: Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose
measure: Area Under the Concentration-Time Curve From Predose to Infinity (AUC0-inf) of MK-8527-TP in PBMCs
timeFrame: Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose
measure: Area Under the Concentration-Time Curve From Predose to Last Measurable Concentration (AUC0-last) of MK-8527-TP in PBMCs
timeFrame: Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose
measure: Maximum Concentration (Cmax) of MK-8527-TP in PBMCs
timeFrame: Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose
measure: Concentration at 168 Hours Postdose (C168) of MK-8527-TP in PBMCs
timeFrame: 168 hours postdose
measure: Time to Maximum Concentration (Tmax) of MK-8527-TP in PBMCs
timeFrame: Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose
measure: Apparent Terminal Half-life (t½) of MK-8527-TP in PBMCs
timeFrame: Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose
measure: AUC0-inf of MK-8527 in Plasma
timeFrame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
measure: AUC0-last of MK-8527 in Plasma
timeFrame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
measure: Clast of MK-8527 in Plasma
timeFrame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
measure: Cmax of MK-8527 in Plasma
timeFrame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
measure: Tmax of MK-8527 in Plasma
timeFrame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
measure: Apparent t½ of MK-8527 in Plasma
timeFrame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
measure: Correlation Between Intracellular C168 of MK-8527-TP in PBMCs and Change From Baseline in Plasma HIV-1 RNA
timeFrame: Predose and 168 hours postdose
Other outcomes:
Locations:
city: București
country: Romania
facility: ARENSIA Exploratory Medicine-Institutul National de Boli Infectioase Matei Bals ( Site 0004)
state: Bucuresti
city: Bloemfontein
country: South Africa
facility: Josha Research ( Site 0003)
state: Free State
city: Johannesburg
country: South Africa
facility: Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0002)
state: Gauteng
city: Cape Town
country: South Africa
facility: Desmond Tutu Health Foundation ( Site 0001)
state: Western Cape
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: