A Clinical Trial of Epizon-701 (EPN-701) in Subjects With End-Stage Renal Disease (ESRD)

A Phase 2 Prospective Safety/Tolerability, Pharmacokinetics, Surrogate Biomarkers as Proxies for Efficacy Trial of EPN-701 in Subjects With Stable End Stage Renal Disease (ESRD) Receiving Outpatient Hemodialysis

Patients with End Stage Renal Disease (ESRD) are prone to early and accelerated vascular calcification. Both the prevalence and extent of the vascular calcification are predictive for cardiovascular morbidity and all-cause mortality in this population. There is a growing body of evidence suggesting that dialysis patients have a primary, functional deficiency of Vitamin K2 as evidenced by reduced levels of circulating biomarkers including carboxylated forms of Matrix Gla Protein (MGP), Osteocalcin, and Fetuin-A, which are important inhibitors of vascular calcification. Decreased levels of Vitamin K2 are known to lead to microvascular calcification and are associated with dermatological and cardiovascular conditions such as calciphylaxis and peripheral arterial disease (PAD).

The purpose of this Phase 2 study is to examine the safety and pharmacokinetics of EPN-701 (menaquinone-7; MK-7) and to assess the effects on certain circulating biomarkers when MK-7 is orally administered once daily for 14 days.

Study Overview

• Status: Completed
• Conditions: End-Stage Renal Disease (ESRD)
• Intervention / Treatment: Drug: EPN-701 (Oral)

Detailed Description

Patients with End Stage Renal Disease (ESRD) are prone to early and accelerated vascular calcification. Both the prevalence and extent of the vascular calcification are predictive for cardiovascular morbidity and all-cause mortality in this population. There is a growing body of evidence suggesting that dialysis patients have a primary, functional deficiency of Vitamin K2 as evidenced by reduced levels of circulating biomarkers including carboxylated forms of Matrix Gla Protein (MGP), Osteocalcin, and Fetuin-A, which are important inhibitors of vascular calcification. Decreased levels of Vitamin K2 are known to lead to microvascular calcification and are associated with dermatological and cardiovascular conditions such as calciphylaxis and peripheral arterial disease (PAD). The purpose of this Phase 2 study is to examine the safety and pharmacokinetics of EPN-701 (menaquinone-7; MK-7) and to assess the effects on certain circulating biomarkers when MK-7 is orally administered once daily for 14 days.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30904
      • Southeastern Clinical Research Institute, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Consenting subjects.
• Adult male and female who were diagnosed with stable ESRD.
• Subjects treated with maintenance hemodialysis at least 3 times a week for at least 3 months prior to the first dose of study drug.
• Clinically stable.

Exclusion Criteria:

• Solid organ transplant.
• Malignancy.
• Severe infection requiring intravenous (IV) antibiotics.
• Any co-existing disease or condition that could have compromised the safety of study participants and/or the integrity of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EPN-701, 10mg orally daily over 14 days; Single arm	Drug: EPN-701 (Oral); MK-7; Other Names: menaquinone-7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Frequency of treatment-emergent Adverse Events and treatment-emergent AEs assessed as related to the study drug.	Through study completion; over 14 days treatment and one week follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of EPN-701.	• Maximum plasma concentration of EPN-701 (Cmax) [ng/mL].	Through study completion; over 14 days treatment and one week follow-up.
Time to maximum plasma concentration of EPN-701.	Time to maximum plasma concentration of EPN-701 (Tmax) (h).	Through study completion; over 14 days treatment and one week follow-up.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in circulating biomarker: Undercarboxylated Matrix Gla Protein (MGP), (pmol/L).	Undercarboxylated MGP (pmol/L).	Through study completion; over 14 days treatment and one week follow-up.

Collaborators and Investigators

• Sponsor: Epizon Pharma, Inc.
• Investigators: Principal Investigator: Mark T Smith, MD, Southeastern Clinical Research Institute, LLC 1521, Anthony Road Augusta, GA 30904

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): April 30, 2021

Study Registration Dates

• First Submitted: February 16, 2022
• First Submitted That Met QC Criteria: March 15, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 18, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Hemostatics; Coagulants; Vitamin MK 7
• Other Study ID Numbers: EPN-701-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No