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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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End-Stage Renal Disease, End-Stage Kidney Disease, Kidney Failure, Chronic

Intervention / Treatment
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* Biological: MK-2060
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: MK-2060<br>MK-2060 administered as a single subcutaneous dose of 30 mg on Day 1 | Biological: MK-2060<br>* MK-2060 lyophilized powder diluted in normal saline and administered subcutaneously<br>|
| Placebo Comparator: Part 1: Placebo<br>Placebo (normal saline) administered as a single subcutaneous dose on Day 1 | Drug: Placebo<br>* Normal saline administered subcutaneously<br>|
| Experimental: Part 2: MK-2060<br>MK-2060 administered as multiple subcutaneous doses on Days 1, 2, 3, 4, 8, 15, and 22. | Biological: MK-2060<br>* MK-2060 lyophilized powder diluted in normal saline and administered subcutaneously<br>|
| Placebo Comparator: Part 2: Placebo<br>Placebo (normal saline) administered as multiple subcutaneous doses on Days 1, 2, 3, 4, 8, 15, and 22. | Drug: Placebo<br>* Normal saline administered subcutaneously<br>|
| Experimental: Part 3: MK-2060<br>MK-2060 administered as a single subcutaneous dose on Day 1 | Biological: MK-2060<br>* MK-2060 lyophilized powder diluted in normal saline and administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 |