Clinical trial NCT05656040: A Study of MK-2060 in Participants With Chronic and/or End-Stage Kidney Disease (MK-2060-011)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: End-Stage Renal Disease
End-Stage Kidney Disease
Kidney Failure, Chronic
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-12-19
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Number of Participants who Experience One or More Bleeding Related Adverse Events (AE)
timeFrame: Up to approximately 104 days
measure: Part 2: Number of Participants who Experience One or More Bleeding Related AEs
timeFrame: Up to approximately 144 days
measure: Part 3: Number of Participants who Experience One or More Bleeding Related AEs
timeFrame: Up to approximately 104 days
measure: Part 1: Number of Participants who Experience One or More AEs
timeFrame: Up to approximately 104 days
measure: Part 2: Number of Participants who Experience One or More AEs
timeFrame: Up to approximately 144 days
measure: Part 3: Number of Participants who Experience One or More AEs
timeFrame: Up to approximately 104 days
measure: Part 1: Number of Participants who Discontinue Study Due to an AE
timeFrame: Up to approximately 104 days
measure: Part 2: Number of Participants who Discontinue Study Due to an AE
timeFrame: Up to approximately 144 days
measure: Part 3: Number of Participants who Discontinue Study Due to an AE
timeFrame: Up to approximately 104 days
measure: Part 1: Area Under the Concentration-Time Curve from 0 to Infinity (AUC0-inf) of MK-2060
timeFrame: 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
measure: Part 2: AUC0-inf of MK-2060
timeFrame: 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
measure: Part 3: AUC0-inf of MK-2060
timeFrame: 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
measure: Part 1: Area Under the Concentration-Time Curve from Time 0 to 168 Hours (AUC0-168) of MK-2060
timeFrame: Pre-dose, 1, 12, 24, 48, 120, and 168 hours post-dose
measure: Part 2: AUC0-168 of MK-2060
timeFrame: Pre-dose, 24, 72, and 168 hours post-dose
measure: Part 3: AUC0-168 of MK-2060
timeFrame: Pre-dose, 1, 12, 24, 48, 120, and 168 hours post-dose
measure: Part 1: Maximum Plasma Concentration (Cmax) of MK-2060
timeFrame: 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
measure: Part 2: Cmax of MK-2060
timeFrame: 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
measure: Part 3: Cmax of MK-2060
timeFrame: 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
measure: Part 1: Plasma Concentration at 168 Hours (C168) of MK-2060
timeFrame: 168 hours post-dose
measure: Part 2: C168 of MK-2060
timeFrame: 168 hours post-dose
measure: Part 3: C168 of MK-2060
timeFrame: 168 hours post-dose
measure: Part 1: Time to Maximum Plasma Concentration (Tmax) of MK-2060
timeFrame: 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
measure: Part 2: Tmax of MK-2060
timeFrame: 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
measure: Part 3: Tmax of MK-2060
timeFrame: 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
measure: Part 1: Terminal Half Life (t1/2) of MK-2060
timeFrame: 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
measure: Part 2: t1/2 of MK-2060
timeFrame: 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
measure: Part 3: t1/2 of MK-2060
timeFrame: 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
measure: Part 1: Apparent Total Clearance (CL/F) of MK-2060
timeFrame: 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
measure: Part 2: CL/F of MK-2060
timeFrame: 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
measure: Part 3: CL/F of MK-2060
timeFrame: 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
measure: Part 1: Apparent Volume of Distribution (Vz/F) of MK-2060
timeFrame: 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
measure: Part 2: Vz/F of MK-2060
timeFrame: 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
measure: Part 3: Vz/F of MK-2060
timeFrame: 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 outcomes:
measure: Part 1: Percent Change from Baseline in Activated Partial Thromboplastin Time (aPTT) of MK-2060
timeFrame: Baseline and 90 days post-dose
measure: Part 2: Percent Change from Baseline in aPTT of MK-2060
timeFrame: Baseline and 130 days post-dose
measure: Part 3: Percent Change from Baseline in aPTT of MK-2060
timeFrame: Baseline and 120 days post-dose
Other outcomes:
Locations:
city: Edgewater
country: United States
facility: Velocity Clinical Research, New Smyrna Beach ( Site 0003)
state: Florida
city: Miami
country: United States
facility: Advanced Pharma CR, LLC ( Site 0006)
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Research, LLC ( Site 0004)
state: Florida
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research, LLC ( Site 0002)
state: Tennessee
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: