A Study of MK-2060 in Participants With Chronic and/or End-Stage Kidney Disease (MK-2060-011)

Kidney Failure, Chronic Clinical Trial

Official title:

A Single-and Multiple Dose Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of Subcutaneous MK-2060 in Participants With Chronic and/or End-Stage Kidney Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05656040
• Other study ID #: 2060-011
• Secondary ID: MK-2060-011
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 8, 2023
• Est. completion date: August 15, 2024

Study information

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

Clinical Trial Summary

This is a three-part study of MK-2060 in participants with chronic and/or end-stage kidney disease. The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of a single subcutaneous dose of MK-2060 in stage 4 chronic kidney disease (CKD4) or stage 5 chronic kidney disease (CKD5) participants in Part 1, of multiple subcutaneous doses in CKD4 or CKD5 participants in Part 2, and of a single subcutaneous dose of MK-2060 in participants with end-stage kidney disease in Part 3. The primary hypothesis is that, in Part 1, the true geometric mean of the area under the concentration-time curve from 0 to infinity (AUC0-inf) after a single-dose of MK-2060 in adult CKD4 or CKD5 participants is at least 11300 nM*hr.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 33
• Est. completion date: August 15, 2024
• Est. primary completion date: August 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• At the time of screening, has stage 4 or 5 chronic kidney disease (Parts 1 and 2) or end-state kidney disease on peritoneal dialysis (Part 3).
• Has a body mass index (BMI) = 18 and = 45 kg/m^2.

Exclusion Criteria:

• Has a history of cancer, including adenocarcinoma, except adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or other malignances which have been successfully treated = 5 years prior to prestudy with appropriate follow-up.
• Has a history of deep vein thrombosis or pulmonary embolism, a history of vascular access thrombosis within 1 month prior to enrollment, or has a personal or family history of bleeding disorder.
• Has a history of gastrointestinal (GI) bleeding, duodenal polyps, or gastric ulcer in the last 5 years or severe hemorrhoidal bleed in the last 3 months.
• Has a history of or current frequent epistaxis within the last 3 months or active gingivitis.
• Has ongoing anticoagulant therapy or antiplatelet therapy. Aspirin is permitted.
• Has planned significant dental procedures at the time of screening or pre-dose or other planned surgical procedures within duration of participation of study.
• Is positive for hepatitis B surface antigen or human immunodeficiency virus (HIV).
• Has had major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-study visit.
• Has a history (participant recall) of receiving any human immunoglobulin preparation such as intravenous immunoglobulin (IVIG) or RhoGAM within the last year.
• Has a history (participant recall) of receiving any biological therapy (including human blood products or monoclonal antibodies; excluding erythropoietin and insulin) within the last 3 months or vaccination within the last 1 month, except the seasonal flu and pneumococcal vaccine or COVID-19 vaccine.

Related Conditions & MeSH terms

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

Intervention

Biological:
• MK-2060
MK-2060 lyophilized powder diluted in normal saline and administered subcutaneously

Drug:
• Placebo
Normal saline administered subcutaneously

Locations

Country	Name	City	State
United States	Velocity Clinical Research, New Smyrna Beach ( Site 0003)	Edgewater	Florida
United States	Alliance for Multispecialty Research, LLC ( Site 0002)	Knoxville	Tennessee
United States	Advanced Pharma CR, LLC ( Site 0006)	Miami	Florida
United States	Genesis Clinical Research, LLC ( Site 0004)	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants who Experience One or More Bleeding Related Adverse Events (AE)	Bleeding related AEs will include any sign or symptom of bleeding, even if not requiring intervention by a medical/healthcare professional, as well as clinically relevant nonmajor bleeding or major bleeding.	Up to approximately 104 days
Primary	Part 2: Number of Participants who Experience One or More Bleeding Related AEs	Bleeding related AEs will include any sign or symptom of bleeding, even if not requiring intervention by a medical/healthcare professional, as well as clinically relevant nonmajor bleeding or major bleeding.	Up to approximately 144 days
Primary	Part 3: Number of Participants who Experience One or More Bleeding Related AEs	Bleeding related AEs will include any sign or symptom of bleeding, even if not requiring intervention by a medical/healthcare professional, as well as clinically relevant nonmajor bleeding or major bleeding.	Up to approximately 104 days
Primary	Part 1: Number of Participants who Experience One or More AEs	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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 104 days
Primary	Part 2: Number of Participants who Experience One or More AEs	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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 144 days
Primary	Part 3: Number of Participants who Experience One or More AEs	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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 104 days
Primary	Part 1: Number of Participants who Discontinue 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 104 days
Primary	Part 2: Number of Participants who Discontinue 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 144 days
Primary	Part 3: Number of Participants who Discontinue 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 104 days
Primary	Part 1: Area Under the Concentration-Time Curve from 0 to Infinity (AUC0-inf) of MK-2060	Blood will be collected at pre-specified time points to determine the AUC0-inf of MK-2060 in plasma.	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Primary	Part 2: AUC0-inf of MK-2060	Blood will be collected at pre-specified time points to determine the AUC0-inf of MK-2060 in plasma.	Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Primary	Part 3: AUC0-inf of MK-2060	Blood will be collected at pre-specified time points to determine the AUC0-inf of MK-2060 in plasma.	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Primary	Part 1: Area Under the Concentration-Time Curve from Time 0 to 168 Hours (AUC0-168) of MK-2060	Blood will be collected at pre-specified time points to determine the AUC0-168 of MK-2060 in plasma from 0 to 168 hours.	Pre-dose, 1, 12, 24, 48, 120, and 168 hours post-dose
Primary	Part 2: AUC0-168 of MK-2060	Blood will be collected at pre-specified time points to determine the AUC0-168 of MK-2060 in plasma from 0 to 168 hours.	Pre-dose, 24, 72, and 168 hours post-dose
Primary	Part 3: AUC0-168 of MK-2060	Blood will be collected at pre-specified time points to determine the AUC0-168 of MK-2060 in plasma from 0 to 168 hours.	Pre-dose, 1, 12, 24, 48, 120, and 168 hours post-dose
Primary	Part 1: Maximum Plasma Concentration (Cmax) of MK-2060	Blood will be collected at pre-specified time points to determine the Cmax of MK-2060 in plasma.	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Primary	Part 2: Cmax of MK-2060	Blood will be collected at pre-specified time points to determine the Cmax of MK-2060 in plasma.	Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Primary	Part 3: Cmax of MK-2060	Blood will be collected at pre-specified time points to determine the Cmax of MK-2060 in plasma.	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Primary	Part 1: Plasma Concentration at 168 Hours (C168) of MK-2060	Blood will be collected at 168 hours post-dose to determine the C168 of MK-2060 in plasma.	168 hours post-dose
Primary	Part 2: C168 of MK-2060	Blood will be collected at 168 hours post-dose to determine the C168 of MK-2060 in plasma.	168 hours post-dose
Primary	Part 3: C168 of MK-2060	Blood will be collected at 168 hours post-dose to determine the C168 of MK-2060 in plasma.	168 hours post-dose
Primary	Part 1: Time to Maximum Plasma Concentration (Tmax) of MK-2060	Blood will be collected at pre-specified time points to determine the Tmax of MK-2060 in plasma.	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Primary	Part 2: Tmax of MK-2060	Blood will be collected at pre-specified time points to determine the Tmax of MK-2060 in plasma.	Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Primary	Part 3: Tmax of MK-2060	Blood will be collected at pre-specified time points to determine the Tmax of MK-2060 in plasma.	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Primary	Part 1: Terminal Half Life (t1/2) of MK-2060	Blood will be collected at pre-specified time points to determine the terminal t1/2 of MK-2060 in plasma.	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Primary	Part 2: t1/2 of MK-2060	Blood will be collected at pre-specified time points to determine the terminal t1/2 of MK-2060 in plasma.	Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Primary	Part 3: t1/2 of MK-2060	Blood will be collected at pre-specified time points to determine the terminal t1/2 of MK-2060 in plasma.	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Primary	Part 1: Apparent Total Clearance (CL/F) of MK-2060	Blood will be collected at pre-specified time points to determine the CL/F of MK-2060 in plasma.	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Primary	Part 2: CL/F of MK-2060	Blood will be collected at pre-specified time points to determine the CL/F of MK-2060 in plasma.	Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Primary	Part 3: CL/F of MK-2060	Blood will be collected at pre-specified time points to determine the CL/F of MK-2060 in plasma.	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Primary	Part 1: Apparent Volume of Distribution (Vz/F) of MK-2060	Blood will be collected at pre-specified time points to determine the Cmax of MK-2060 in plasma	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Primary	Part 2: Vz/F of MK-2060	Blood will be collected at pre-specified time points to determine the Cmax of MK-2060 in plasma	Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Primary	Part 3: Vz/F of MK-2060	Blood will be collected at pre-specified time points to determine the Cmax of MK-2060 in plasma	Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Secondary	Part 1: Percent Change from Baseline in Activated Partial Thromboplastin Time (aPTT) of MK-2060	Blood will be collected at pre-specified time points to determine the aPTT of MK-2060 in plasma.	Baseline and 90 days post-dose
Secondary	Part 2: Percent Change from Baseline in aPTT of MK-2060	Blood will be collected at pre-specified time points to determine the aPTT of MK-2060 in plasma.	Baseline and 130 days post-dose
Secondary	Part 3: Percent Change from Baseline in aPTT of MK-2060	Blood will be collected at pre-specified time points to determine the aPTT of MK-2060 in plasma.	Baseline and 120 days post-dose

External Links

•   Merck Clinical Trials Information