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A Study to Evaluate the Efficacy and Safety of DA-1229 (Evogliptin) in Patient's Calcific Aortic Valve Disease With Mild to Moderate Aortic Stenosis (EVOID-AS)

Primary Purpose

Calcific Aortic Valve Disease

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Evogliptin
Evogliptin
Placebo
Sponsored by
REDNVIA Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Calcific Aortic Valve Disease

Eligibility Criteria

35 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female adult ≥ 35 years of age at time of screening.
  2. Subject has calcific aortic valve disease with mild to moderate aortic stenosis as defined by

    • Doppler echocardiography results: Aortic Valve mean pressure gradient between 10-30 mmHg and Aortic Valve Area ≥ 1.2 and ≤ 2.0 cm2 on TTE within 2 weeks prior to randomization and,
    • Cardiac Compute Tomography (CT) test results: aortic valve calcium score (Agatston score) ≥ 200 AU at baseline cardiac CT within 1 month prior to randomization
  3. Subject provides written informed consent prior to initiation of any study procedures.
  4. Subject understands and agrees to comply with planned study procedures.

Exclusion Criteria:

  1. Subject has concomitant moderate or more aortic valve regurgitation.
  2. Subject has concomitant moderate or severe mitral or tricuspid valve disease.
  3. Subjects has left ventricular ejection fraction < 50%.
  4. Subject previous history of aortic valve surgery.
  5. Subject has NYHA class III or IV heart failure.
  6. Subjects whose alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 times the upper limit of normal range.
  7. Subjects who cannot undergo Cardiac CT.
  8. Subjects whose life expectancy is < 2 years.
  9. Subjects with ESRD (End-stage Renal Disease) defined as eGFR (calculated using MDRD equation) ≤ 30 mL/min/1.73m2 or in need of dialysis.
  10. Subject has diabetes mellitus.
  11. Subject has history of pancreatitis.
  12. Subjects who are currently taking or anticipated to take any of the following medications for the duration of the study:

    • Insulin, DPP4 inhibitor, oral hypoglycemic agent
    • Vitamin K
    • Bisphosphonate
    • Any medications that impact hepatic metabolism, giving rise to drug-drug interaction (with the exception of focal treatment) CYP3A4 inducer: barbiturates, rifampicin, carbamazepine, phenytoin
  13. Subjects with history of severe allergic reaction to DPP4 inhibitors including anaphylaxis and angioedema
  14. Subjects with galactose intolerance, lapp lactase deficiency, and glucose-galactose malabsorption
  15. Subjects with history of severe cerebrovascular diseases (such as cerebral infarction or transient ischemic attack), severe cardiovascular diseases (such as unstable angina, myocardial infarction and life-threatening arrhythmia) within 6 months of screening.
  16. Subjects with history of malignant tumor within the past 3 years prior to Screening Visit (Visit 1) unless cure is expected.
  17. Subjects with history of drug or alcohol abuse. History of cannabis/Marijuana use including recreational use in the last 6 months and an unwillingness to abstain during the course of the study.

    o Note: Alcohol abuse is a pattern of drinking that result in harm to one's health, interpersonal relationships, or ability to work. Manifestations of alcohol abuse include the following: Failure to fulfill major responsibilities at work, school, or home, drinking in dangerous situations, such as drinking while driving or operating machinery, legal problems related to alcohol, such as being arrested for drinking while driving or for physically hurting someone while drunk and continued drinking despite ongoing relationship problems that are caused or worsened by drinking

  18. Subjects with history of medication non-compliance
  19. Pregnant or lactating women
  20. Subjects who used investigational drugs or devices within 4 weeks prior to screening or investigational biologics within the last 6 months prior to screening.
  21. Inability to provide informed consent or to comply with test requirements
  22. Subjects with physical (severe hepatic, cardiac, renal, pulmonary, hematological, endocrine, gastrointestinal, etc. conditions) or mental (cognitive, psychiatric, etc. conditions) conditions that may impact their ability to take part in the study.
  23. Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment
  24. Women of child-bearing age who are sexually active but decline to take proper contraceptive measures during the study period

    • Note: To be eligible for the study, Women of childbearing potential (WOCBP) and Women not of childbearing potential are eligible to participate. Both women of childbearing potential and women of no childbearing potential should use an approved method of birth control and agrees to continue to use this method for the duration of the study (and for 30 days after taking the last dose of investigational product).
    • Acceptable methods of contraception include abstinence, female subject/partner's use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method (WOCBP only), female subject/partner's use of an intrauterine device (IUD), or if the female subject/partner is surgically sterile or 2 years post-menopausal. All male subjects/partners must agree to consistently and correctly use a condom for the duration of the study and for 30 days after taking the study drug. In addition, subjects may not ova or donate sperm for the duration of the study and for 30 days after taking the last dose investigational product.

Sites / Locations

  • University of Southern CaliforniaRecruiting
  • Baycare Health systemsRecruiting
  • Massachusetts General HospitalRecruiting
  • University of MichiganRecruiting
  • Beaumont Hospital, Royal OakRecruiting
  • Mayo ClinicRecruiting
  • Ichan School of MedicineRecruiting
  • University of Pittsburgh Medical CenterRecruiting
  • Aurora Research InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

Placebo

DA-1229 5mg

DA-1229 10 mg

Arm Description

Outcomes

Primary Outcome Measures

Aortic valve calcification as measured by change from baseline in Agatston arbitrary unit (AU) using cardiac computed tomography (CT) at 104 weeks

Secondary Outcome Measures

Time-to-major adverse cardiovascular events of cardiac death, non- fatal myocardial infarction, heart failure hospitalization and stroke
Time-to-symptom onset
Time-to-AV intervention to treat aortic stenosis including AV replacement
Aortic valve calcification as measured by Agatston AU using cardiac computed tomography (CT) at week 52
Change in aortic stenosis severity as measured by aortic valve area (AVA) using echocardiography at week 52 as compared to baseline
Change in aortic stenosis severity as measured by aortic valve area (AVA) using echocardiography at week 104 as compared to baseline
Change in aortic stenosis severity as measured by peak transaortic velocity using echocardiography at week 52 as compared to baseline
Change in aortic stenosis severity as measured by peak transaortic velocity using echocardiography at week 104 as compared to baseline
Change in aortic stenosis severity as measured by mean pressure gradient using echocardiography at week 52 as compared to baseline
Change in aortic stenosis severity as measured by mean pressure gradient using echocardiography at week 104 as compared to baseline
Change in aortic stenosis severity as measured by dimensionless velocity using echocardiography at week 52 as compared to baseline
Change in aortic stenosis severity as measured by dimensionless velocity using echocardiography at week 104 as compared to baseline
Change in coronary artery and mitral annulus calcium score at week 52 as compared to baseline
Change in coronary artery and mitral annulus calcium score at week 104 as compared to baseline

Full Information

First Posted
October 20, 2021
Last Updated
April 4, 2023
Sponsor
REDNVIA Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05143177
Brief Title
A Study to Evaluate the Efficacy and Safety of DA-1229 (Evogliptin) in Patient's Calcific Aortic Valve Disease With Mild to Moderate Aortic Stenosis (EVOID-AS)
Official Title
An Adaptive Phase 2/3 Multicenter, Double-Blind, Placebo-Controlled, Randomized, Parallel, 3 Arm Study to Evaluate the Efficacy and Safety of DA-1229 (Evogliptin) in Patient's Calcific Aortic Valve Disease With Mild to Moderate Aortic Stenosis (EVOID-AS)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 27, 2022 (Actual)
Primary Completion Date
May 15, 2026 (Anticipated)
Study Completion Date
December 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
REDNVIA Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is an adaptive Phase 2/3 multicenter, double-blind, placebo-controlled, randomized, parallel, 3 arm study to evaluate the efficacy and safety of DA-1229 compared to placebo in patients with calcific aortic valve disease with mild to moderate aortic stenosis. There are 3 arms in this study to which patients will be randomized in a ratio of 1:1:1 to receive the DA-1229 or placebo orally once daily for a period of 104 weeks . the 3 arms are: placebo, DA-1229 5mg GroupDA-1229 10 mg Group. The study will have three phases: Screening Period (up to 4 weeks), Treatment Period (104 weeks), and Follow-Up Period (2-4 weeks). Total Study Duration is112 Weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Calcific Aortic Valve Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
867 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
DA-1229 5mg
Arm Type
Active Comparator
Arm Title
DA-1229 10 mg
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Evogliptin
Other Intervention Name(s)
DA-1229
Intervention Description
DA-1229 5mg, 1 tab
Intervention Type
Drug
Intervention Name(s)
Evogliptin
Other Intervention Name(s)
DA-1229
Intervention Description
DA-1229 10 mg, 1 tab
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
DA-1229 Placebo, 1 tab
Primary Outcome Measure Information:
Title
Aortic valve calcification as measured by change from baseline in Agatston arbitrary unit (AU) using cardiac computed tomography (CT) at 104 weeks
Time Frame
at 104 weeks
Secondary Outcome Measure Information:
Title
Time-to-major adverse cardiovascular events of cardiac death, non- fatal myocardial infarction, heart failure hospitalization and stroke
Time Frame
104 weeks
Title
Time-to-symptom onset
Time Frame
104 weeks
Title
Time-to-AV intervention to treat aortic stenosis including AV replacement
Time Frame
104 weeks
Title
Aortic valve calcification as measured by Agatston AU using cardiac computed tomography (CT) at week 52
Time Frame
at week 52
Title
Change in aortic stenosis severity as measured by aortic valve area (AVA) using echocardiography at week 52 as compared to baseline
Time Frame
at week 52 as compared to baseline
Title
Change in aortic stenosis severity as measured by aortic valve area (AVA) using echocardiography at week 104 as compared to baseline
Time Frame
at week 104 as compared to baseline
Title
Change in aortic stenosis severity as measured by peak transaortic velocity using echocardiography at week 52 as compared to baseline
Time Frame
at week 52 as compared to baseline
Title
Change in aortic stenosis severity as measured by peak transaortic velocity using echocardiography at week 104 as compared to baseline
Time Frame
at week 104 as compared to baseline
Title
Change in aortic stenosis severity as measured by mean pressure gradient using echocardiography at week 52 as compared to baseline
Time Frame
at week 52 as compared to baseline
Title
Change in aortic stenosis severity as measured by mean pressure gradient using echocardiography at week 104 as compared to baseline
Time Frame
at week 104 as compared to baseline
Title
Change in aortic stenosis severity as measured by dimensionless velocity using echocardiography at week 52 as compared to baseline
Time Frame
at week 52 as compared to baseline
Title
Change in aortic stenosis severity as measured by dimensionless velocity using echocardiography at week 104 as compared to baseline
Time Frame
at week 104 as compared to baseline
Title
Change in coronary artery and mitral annulus calcium score at week 52 as compared to baseline
Time Frame
at week 52 as compared to baseline
Title
Change in coronary artery and mitral annulus calcium score at week 104 as compared to baseline
Time Frame
at week 104 as compared to baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female adult ≥ 35 years of age at time of screening. Subject has calcific aortic valve disease with mild to moderate aortic stenosis as defined by Doppler echocardiography results: Aortic Valve mean pressure gradient between 10-30 mmHg and Aortic Valve Area ≥ 1.2 and ≤ 2.0 cm2 on TTE within 2 weeks prior to randomization and, Cardiac Compute Tomography (CT) test results: aortic valve calcium score (Agatston score) ≥ 200 AU at baseline cardiac CT within 1 month prior to randomization Subject provides written informed consent prior to initiation of any study procedures. Subject understands and agrees to comply with planned study procedures. Exclusion Criteria: Subject has concomitant moderate or more aortic valve regurgitation. Subject has concomitant moderate or severe mitral or tricuspid valve disease. Subjects has left ventricular ejection fraction < 50%. Subject previous history of aortic valve surgery. Subject has NYHA class III or IV heart failure. Subjects whose alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 times the upper limit of normal range. Subjects who cannot undergo Cardiac CT. Subjects whose life expectancy is < 2 years. Subjects with ESRD (End-stage Renal Disease) defined as eGFR (calculated using MDRD equation) ≤ 30 mL/min/1.73m2 or in need of dialysis. Subject has diabetes mellitus. Subject has history of pancreatitis. Subjects who are currently taking or anticipated to take any of the following medications for the duration of the study: Insulin, DPP4 inhibitor, oral hypoglycemic agent The use of SGLT2 inhibitors is allowed as long as the indication for its use is for treatment of heart failure and not diabetes mellitus. Injectable GLP-1 agonists indicated for weight loss treatment in nondiabetics are also allowed. Vitamin K ▪ Subjects taking over-the-counter multivitamins containing ≤ 90 mcg/day vitamin K will be allowed to continue use during the study. Bisphosphonate Any medications that impact hepatic metabolism, by way of inducing CYP3A4 system, giving rise to drug-drug interaction (with the exception of focal treatment) ▪ CYP3A4 inducer: barbiturates (phenobarbital), rifampicin/rifabutin, carbamazepine, phenytoin, primidone, St. John's Wort, Efavirenz, griseofulvin, and chronic (>1 month) supraphysiologic glucocorticoid use (>7.5 mg/day prednisone or equivalent glucocorticoid dosing). Subjects with history of severe allergic reaction to DPP4 inhibitors including anaphylaxis and angioedema Subjects with galactose intolerance, lapp lactase deficiency, and glucose-galactose malabsorption Subjects with history of severe cerebrovascular diseases (such as cerebral infarction or transient ischemic attack), severe cardiovascular diseases (such as unstable angina, myocardial infarction and life-threatening arrhythmia) within 6 months of screening. Subjects with history of malignant tumor within the past 3 years prior to Screening Visit (Visit 1) unless cure is expected. Subjects with history of drug or alcohol abuse. History of cannabis/Marijuana use including recreational use in the last 6 months and an unwillingness to abstain during the course of the study. o Note: Alcohol abuse is a pattern of drinking that result in harm to one's health, interpersonal relationships, or ability to work. Manifestations of alcohol abuse include the following: Failure to fulfill major responsibilities at work, school, or home, drinking in dangerous situations, such as drinking while driving or operating machinery, legal problems related to alcohol, such as being arrested for drinking while driving or for physically hurting someone while drunk and continued drinking despite ongoing relationship problems that are caused or worsened by drinking Subjects with history of medication non-compliance Pregnant or lactating women Subjects who used investigational drugs or devices within 4 weeks prior to screening or investigational biologics within the last 6 months prior to screening. Inability to provide informed consent or to comply with test requirements Subjects with physical (severe hepatic, cardiac, renal, pulmonary, hematological, endocrine, gastrointestinal, etc. conditions) or mental (cognitive, psychiatric, etc. conditions) conditions that may impact their ability to take part in the study. Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment Women of child-bearing age who are sexually active but decline to take proper contraceptive measures during the study period Note: To be eligible for the study, Women of childbearing potential (WOCBP) and Women not of childbearing potential are eligible to participate. Both women of childbearing potential and women of no childbearing potential should use an approved method of birth control and agrees to continue to use this method for the duration of the study (and for 30 days after taking the last dose of investigational product). Acceptable methods of contraception include abstinence, female subject/partner's use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method (WOCBP only), female subject/partner's use of an intrauterine device (IUD), or if the female subject/partner is surgically sterile or 2 years post-menopausal. All male subjects/partners must agree to consistently and correctly use a condom for the duration of the study and for 30 days after taking the study drug. In addition, subjects may not ova or donate sperm for the duration of the study and for 30 days after taking the last dose investigational product.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anand Balasubramanian, B.Pharm
Phone
(301) 956 2531
Email
anandb@amarexcro.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jae K Oh, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melissa Ramos
Email
melissa.ramos@med.usc.edu
Facility Name
Baycare Health systems
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33755
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Fisher
Email
susan.fisher1@baycare.org
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Omar Hamam
Email
ohamam@mgh.harvard.edu
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Allison Schley
Email
schleya@med.umich.edu
Facility Name
Beaumont Hospital, Royal Oak
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jon Teefey
Email
jon.teefey@beaumont.org
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Halley Davison
Email
davison.halley@mayo.edu
Facility Name
Ichan School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10025
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amber Jin
Email
amber.jin@mountsinai.org
Facility Name
University of Pittsburgh Medical Center
City
Mechanicsburg
State/Province
Pennsylvania
ZIP/Postal Code
17050
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amy Worley
Email
worleyas@upmc.edu
Facility Name
Aurora Research Institute
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sara\ Anderson
Email
sara.klein@aah.org

12. IPD Sharing Statement

Learn more about this trial

A Study to Evaluate the Efficacy and Safety of DA-1229 (Evogliptin) in Patient's Calcific Aortic Valve Disease With Mild to Moderate Aortic Stenosis (EVOID-AS)

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