Single Dose Study of MK-2060 to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Older Japanese Participants on Dialysis (MK-2060-012)

A Single-dose Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-2060 in Japanese Older Participants With End-stage Renal Disease on Dialysis.

The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of MK-2060 after a single dose intravenous (IV) administration in Japanese older participants with end stage renal disease (ESRD) on dialysis. There is no primary hypothesis for this study.

Study Overview

• Status: Completed
• Conditions: Kidney Failure, Chronic; End-Stage Renal Disease (ESRD); End-Stage Kidney Disease (ESKD)
• Intervention / Treatment: Drug: Placebo; Biological: MK-2060

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Japan
  • Fukuoka, Japan, 815-8555
    • Japanese Red Cross Fukuoka Hospital ( Site 1214)
  • Yamagata, Japan, 990-0834
    • Yamagata Tokushukai Hospital ( Site 1201)
  • Aichi
    • Kasugai, Aichi, Japan, 486-8510
      • Kasugai Municipal Hospital ( Site 1203)
    • Nagoya, Aichi, Japan, 455-8530
      • Chubu Rosai Hospital ( Site 1202)
    • Nagoya, Aichi, Japan, 457-8511
      • Kojunkai Daido Hospital ( Site 1207)
  • Gunma
    • Maebashi, Gunma, Japan, 371-0046
      • Jomo Ohashi Clinic ( Site 1210)
  • Ibaraki
    • Kasama, Ibaraki, Japan, 309-1793
      • Ibaraki Prefectural Central Hospital ( Site 1211)
  • Kanagawa
    • Kamakura, Kanagawa, Japan, 247-8533
      • Shonan Kamakura General Hospital ( Site 1205)
  • Nagano
    • Matsumoto, Nagano, Japan, 390-1401
      • Matsumoto City Hospital ( Site 1209)
  • Oita
    • Beppu, Oita, Japan, 874-0937
      • Keiaikai Nakamura Hospital ( Site 1213)
  • Shiga
    • Kusatsu, Shiga, Japan, 525-8585
      • Omi Fureai Hospital ( Site 1204)
  • Tokyo
    • Ota, Tokyo, Japan, 146-8531
      • Ikegami General Hospital ( Site 1206)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Japanese descent with all 2 biological parents of Japanese descent
• On hemodialysis (HD) or hemodiafiltration (HDF) with single-pool Kt/V (spKt/V) ≥1.2, using arteriovenous (AV) fistula or AV graft ≥3 months prior to Screening 1 at a healthcare center, and is on the same dialysis regimen ≥2 weeks prior to Screening 1
• Be judged to plan to continue or anticipate the use of the current AV fistula or AV graft until the poststudy visit

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• On peritoneal dialysis or other dialysis modalities except for HD and HDF
• History of deep vein thrombosis or pulmonary embolism
• History of vascular access thrombosis within 1 month prior to Screening 1
• Personal or family history of bleeding disorder
• History of GI bleeding, duodenal polyps or active gastroduodenal ulcer within 5 years prior to Screening 1, or history of severe hemorrhoidal bleed within 3 months prior to Screening 1
• History of frequent epistaxis within 3 months prior to Screening 1 or active gingivitis
• At the time of screening or predose, planned significant dental procedures, or other planned surgical procedures within duration of participation in the trial
• History of receiving any human immunoglobulin preparation such as intravenous immunoglobulin (IVIG) or a brand of Rho(D) immune globulin (RhoGAM) within 1 year prior to Screening 1
• History of receiving any biological therapy within 3 months prior to Screening 1, or vaccination within 1 month prior to the dose of study intervention
• Requires or anticipates requiring the use of following prohibited medications until the poststudy visit: anticoagulants, antiplatelet medications and non-steroidal anti-inflammatory drugs (NSAIDs)
• Participated in another investigational study within 1 month prior to Screening 1
• Has blood coagulation test (activated partial thromboplastin time [aPTT] or prothrombin time [PT]) above 1.2X upper limit of normal (ULN) at Screening 1 from the central laboratory for safety

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-2060; Participants receive MK-2060 50 mg via a single intravenous (IV) infusion over 60-minutes.	Biological: MK-2060; Lyophilized powder diluted in normal saline for IV infusion
Placebo Comparator: Placebo; Participants receive a single IV saline infusion over 60 minutes.	Drug: Placebo; IV infusion; Other Names: Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who experience an AE will be reported.	Up to approximately 164 days
Number of Participants Who Discontinue Study Due to an AE	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who discontinue study due to an AE will be reported.	Up to approximately 164 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve of MK-2060 From Time 0 to Infinity (AUC 0-inf)	Blood samples will be collected at specified intervals for the determination of AUC0-inf. AUC0-inf is defined as the area under the concentration-time curve of pembrolizumab from time zero to infinity.	Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to Last (AUC0-last)	Blood samples will be collected at specified intervals for the determination of AUC0-last. AUC0-last is defined as the area under the plasma concentration-time curve from time zero to time of last measurable concentration of MK-2060.	Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
Area Under the Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours Postdose (AUC0-168)	Blood samples will be collected at specified intervals for the determination of AUC0-168. AUC0-168 is defined as the area under the concentration-time curve of MK-2060 from time zero to 168 hours.	Predose and 1, 12, 24, 48, 52, 96, and 168 hours postdose
Maximum Concentration (Cmax) of MK-2060	Blood samples will be collected at specified intervals for the determination of Cmax. Cmax is defined as the maximum concentration of MK-2060 reached.	Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
Concentration at 168 Hours (C168) Postdose of MK-2060	Blood samples will be collected at specified intervals for the determination of C168. C168 is defined as the maximum concentration of MK-2060 reached at 168 hours postdose.	Predose and 1, 12, 24, 48, 52, 96, and 168 hours postdose
Time to Maximum Concentration (Tmax) of MK-2060	Blood samples will be collected at specified intervals for the determination of Tmax. Tmax is defined as time to the maximum concentration of MK-2060 reached.	Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
Time of the Last Measurable Plasma Concentration (Tlast) of MK-2060	Blood samples will be collected at specified intervals for the determination of Tlast. Tlast is defined as the time to the last measurable concentration of MK-2060 reached.	Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
Terminal Half-Life (t ½) of MK-2060	Blood samples will be collected at specified intervals for the determination of t½. t½ is defined as the time required to divide the MK-2060 plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-2060.	Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
Clearance (CL) of MK-2060	Blood samples will be collected at specified intervals for the determination of CL. CL is the volume of plasma from which the study drug is completely removed per unit time.	Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
Volume of Distribution (Vz) of MK-2060	Blood samples will be collected at specified intervals for the determination of Vz. Vz is the apparent volume of distribution during the terminal phase.	Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
Change From Baseline in Activated Partial Thromboplastin Time (aPTT)	Blood samples will be collected for the determination of aPTT. Change from baseline in aPTT up to 150 days will be reported.	Baseline and up to 150 days

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

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2023
• Primary Completion (Actual): February 15, 2024
• Study Completion (Actual): February 15, 2024

Study Registration Dates

• First Submitted: March 3, 2023
• First Submitted That Met QC Criteria: March 3, 2023
• First Posted (Actual): March 15, 2023

Study Record Updates

• Last Update Posted (Actual): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: 2060-012; MK-2060-012 (Other Identifier: Merck); jRCT2041230025 (Registry Identifier: jRCT)

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