Clinical trial NCT05285787: A Clinical Trial of Epizon-701 (EPN-701) in Subjects With End-Stage Renal Disease (ESRD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: End-Stage Renal Disease (ESRD)
Lead sponsor: Epizon Pharma, Inc.
Sponsor class: OTHER
First posted: 2022-03-18
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Through study completion; over 14 days treatment and one week follow up.
Secondary outcomes:
measure: Plasma Concentrations of EPN-701.
timeFrame: Through study completion; over 14 days treatment and one week follow-up.
measure: Time to Maximum Plasma Concentration of EPN-701.
timeFrame: Through study completion; over 14 days treatment and one week follow-up.
Other outcomes:
measure: Change From Baseline to Day 15 in Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L).
timeFrame: Day 1 to Day 15
measure: Change From Baseline to Day 22 in Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L).
timeFrame: Day 1 to Day 22
measure: Mean Value of Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L) at Day 22.
timeFrame: Day 22
measure: Mean Measure of Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L).
timeFrame: Day 15
Locations:
city: Augusta
country: United States
facility: Southeastern Clinical Research Institute, LLC
state: Georgia
Study officials:
affiliation: Southeastern Clinical Research Institute, LLC 1521, Anthony Road Augusta, GA 30904
name: Mark T Smith, MD
role: PRINCIPAL_INVESTIGATOR
References: