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

Kidney Failure, Chronic Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05769595
• Other study ID #: 2060-012
• Secondary ID: MK-2060-012jRCT2
• Status: Completed
• Phase: Phase 1
• Start date: June 14, 2023
• Est. completion date: February 15, 2024

Study information

• Verified date: February 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: February 15, 2024
• Est. primary completion date: February 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• End-Stage Renal Disease (ESRD)
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Biological:
• MK-2060
Lyophilized powder diluted in normal saline for IV infusion

Drug:
• Placebo
IV infusion

Locations

Country	Name	City	State
Japan	Keiaikai Nakamura Hospital ( Site 1213)	Beppu	Oita
Japan	Japanese Red Cross Fukuoka Hospital ( Site 1214)	Fukuoka
Japan	Shonan Kamakura General Hospital ( Site 1205)	Kamakura	Kanagawa
Japan	Ibaraki Prefectural Central Hospital ( Site 1211)	Kasama	Ibaraki
Japan	Kasugai Municipal Hospital ( Site 1203)	Kasugai	Aichi
Japan	Omi Fureai Hospital ( Site 1204)	Kusatsu	Shiga
Japan	Jomo Ohashi Clinic ( Site 1210)	Maebashi	Gunma
Japan	Matsumoto City Hospital ( Site 1209)	Matsumoto	Nagano
Japan	Chubu Rosai Hospital ( Site 1202)	Nagoya	Aichi
Japan	Kojunkai Daido Hospital ( Site 1207)	Nagoya	Aichi
Japan	Ikegami General Hospital ( Site 1206)	Ota	Tokyo
Japan	Yamagata Tokushukai Hospital ( Site 1201)	Yamagata

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Merck Clinical Trials Information