RECRUITING

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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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is an adaptive Phase 2/3 multicenter, double-blind, placebo-controlled, randomized, parallel, 2 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 2 arms in this study to which patients will be randomized in a ratio of 1:1 to receive the DA-1229 or placebo orally once daily for a period of 104 weeks. The 2 arms are: placebo and DA-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.

Official Title

An Adaptive Phase 2/3 Multicenter, Double-Blind, Placebo-Controlled, Randomized, Parallel, 2 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)

Quick Facts

Study Start:2022-06-27

Study Completion:2026-12-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05143177

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:35 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 (AVCS) ≥ 200 AU at baseline cardiac CT within 4 weeks 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.	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 \&lt; 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) \&gt; 2.5 times the upper limit of normal range. 7. Subjects who cannot undergo Cardiac CT. 8. Subjects whose life expectancy is \&lt; 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 Type 1 diabetes mellitus. 11. Subject has a history of diabetic ketoacidosis (DKA). 12. Subject has a history of severe hypoglycemia (blood glucose levels \&lt; 54 mg/dl) within the previous six months prior to screening. 13. Subject has pancreatic Amylase isoenzyme and/or Lipase elevation ≥ 3x the upper limit of normal (ULN) at screening or baseline visit, or subject has a history of pancreatitis 14. Subjects who are currently taking or anticipated to take any of the following medications for the duration of the study: * Strong CYP3A4 inducers\* including but not limited to barbiturates (phenobarbital), rifampicin/rifabutin, carbamazepine, phenytoin, primidone, St. John's Wort, Efavirenz, griseofulvin, and chronic (\&gt;1 month) supraphysiologic glucocorticoid use (\&gt;7.5 mg/day prednisone or equivalent glucocorticoid dosing). * Strong CYP3A4 inhibitors\including but not limited to protease inhibitors for treatment of HIV/HCV (such as ritonavir, lopinavir, atazanavir, etc.), chronic systemic use of azole antifungals (ketoconazole, fluconazole, itraconazole, voriconazole) and clarithromycin Note: Short-term/temporary use of clarithromycin, azole antifungals or Paxlovid (for treatment of COVID-19) is allowed, but temporary study drug hold during the course of these treatment would be necessary. 15. Subjects with history of severe allergic reaction to DPP4 inhibitors including anaphylaxis and angioedema. 16. Subjects with galactose intolerance, lapp lactase deficiency, and glucose-galactose malabsorption. 17. 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. 18. Subjects with history of malignant tumor within the past 3 years prior to Screening Visit (Visit 1) unless cure is expected. 19. 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. 20. Subjects with history of medication non-compliance. 21. Pregnant or lactating women. 22. Subjects who used investigational drugs or devices within 4 weeks or investigational biologics within the last 6 months prior to screening and for the duration of the study. 23. Inability to provide informed consent or to comply with test requirements. 24. 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. 25. Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment. 26. Women of child-bearing age who are sexually active but decline to take proper contraceptive measures during the study period, unless the female is post-menopausal for at least 2 years or are surgically sterile. Note: Women of childbearing potential (WOCBP) and Women not of childbearing potential are eligible to participate. Women of 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\&#39;s use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method (WOCBP only), female subject/partner\&#39;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 of WOCBP 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 donate ova or donate sperm for the duration of the study and for 30 days after taking the last dose investigational product. * Voluntary withdrawal of his/her informed consent * Administration of any prohibited medication unless otherwise approved by the investigator(s) * Serious adverse event or adverse drug reaction that causes withdrawal from the study, such as development of acute pancreatitis investigator(s) * Any evidence of pancreatic inflammation on pancreatic imaging (CT Scan or Magnetic resonance cholangiopancreatography (MRCP) or Ultrasound) * Severe breach against this protocol such as breach of any inclusion or exclusion criteria * When Investigator judges aortic valve surgery or procedure is necessary due to progression of disease as per the Critical Pathways presented in American and European Society of Cardiology * Failure to trace the subject - out of contact, etc. - for follow-up observation * Pregnancy * Discontinuation of study by the Sponsor

Inclusion Criteria

Exclusion 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 (AVCS) ≥ 200 AU at baseline cardiac CT within 4 weeks 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.

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 \&lt; 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) \&gt; 2.5 times the upper limit of normal range.
7. Subjects who cannot undergo Cardiac CT.
8. Subjects whose life expectancy is \&lt; 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 Type 1 diabetes mellitus.
11. Subject has a history of diabetic ketoacidosis (DKA).
12. Subject has a history of severe hypoglycemia (blood glucose levels \&lt; 54 mg/dl) within the previous six months prior to screening.
13. Subject has pancreatic Amylase isoenzyme and/or Lipase elevation ≥ 3x the upper limit of normal (ULN) at screening or baseline visit, or subject has a history of pancreatitis
14. Subjects who are currently taking or anticipated to take any of the following medications for the duration of the study:
* Strong CYP3A4 inducers\* including but not limited to barbiturates (phenobarbital), rifampicin/rifabutin, carbamazepine, phenytoin, primidone, St. John's Wort, Efavirenz, griseofulvin, and chronic (\&gt;1 month) supraphysiologic glucocorticoid use (\&gt;7.5 mg/day prednisone or equivalent glucocorticoid dosing).
* Strong CYP3A4 inhibitors\*including but not limited to protease inhibitors for treatment of HIV/HCV (such as ritonavir, lopinavir, atazanavir, etc.), chronic systemic use of azole antifungals (ketoconazole, fluconazole, itraconazole, voriconazole) and clarithromycin Note: Short-term/temporary use of clarithromycin, azole antifungals or Paxlovid (for treatment of COVID-19) is allowed, but temporary study drug hold during the course of these treatment would be necessary.
15. Subjects with history of severe allergic reaction to DPP4 inhibitors including anaphylaxis and angioedema.
16. Subjects with galactose intolerance, lapp lactase deficiency, and glucose-galactose malabsorption.
17. 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.
18. Subjects with history of malignant tumor within the past 3 years prior to Screening Visit (Visit 1) unless cure is expected.
19. 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.
20. Subjects with history of medication non-compliance.
21. Pregnant or lactating women.
22. Subjects who used investigational drugs or devices within 4 weeks or investigational biologics within the last 6 months prior to screening and for the duration of the study.
23. Inability to provide informed consent or to comply with test requirements.
24. 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.
25. Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment.
26. Women of child-bearing age who are sexually active but decline to take proper contraceptive measures during the study period, unless the female is post-menopausal for at least 2 years or are surgically sterile.
* Note: Women of childbearing potential (WOCBP) and Women not of childbearing potential are eligible to participate. Women of 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\&#39;s use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method (WOCBP only), female subject/partner\&#39;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 of WOCBP 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 donate ova or donate sperm for the duration of the study and for 30 days after taking the last dose investigational product.
* Voluntary withdrawal of his/her informed consent
* Administration of any prohibited medication unless otherwise approved by the investigator(s)
* Serious adverse event or adverse drug reaction that causes withdrawal from the study, such as development of acute pancreatitis investigator(s)
* Any evidence of pancreatic inflammation on pancreatic imaging (CT Scan or Magnetic resonance cholangiopancreatography (MRCP) or Ultrasound)
* Severe breach against this protocol such as breach of any inclusion or exclusion criteria
* When Investigator judges aortic valve surgery or procedure is necessary due to progression of disease as per the Critical Pathways presented in American and European Society of Cardiology
* Failure to trace the subject - out of contact, etc. - for follow-up observation
* Pregnancy
* Discontinuation of study by the Sponsor

Contacts and Locations

Study Contact

Nima Sabbaghian, MD

CONTACT

301-528-7000

nimas@amarexcro.com

Principal Investigator

Jae K Oh, MD

PRINCIPAL_INVESTIGATOR

Mayo Clinic

Study Locations (Sites)

Mayo Clinic, AZ

Phoenix, Arizona, 85054

United States

University of Southern California

Los Angeles, California, 90033

United States

University of Colorado

Aurora, Colorado, 80045

United States

Mayo Clinic, FL

Jacksonville, Florida, 32224

United States

Baycare Health systems

Safety Harbor, Florida, 34695

United States

Northside Hospital

Atlanta, Georgia, 30342

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

University of Michigan

Ann Arbor, Michigan, 48109

United States

Henry Ford Health System

Detroit, Michigan, 48202

United States

Beaumont Hospital, Royal Oak

Royal Oak, Michigan, 48073

United States

Mayo Clinic

Rochester,, Minnesota, 55905

United States

Hackensack Meridian Health

Hackensack, New Jersey, 07601

United States

Rutgers- Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901

United States

Ichan School of Medicine

New York, New York, 10025

United States

Stony brook

Stony Brook, New York, 11974

United States

Christ Hospital

Cincinnati, Ohio, 45219

United States

OhioHealth Research Institute

Columbus, Ohio, 43214

United States

Oregon Health & Science University

Portland, Oregon, 97239

United States

University of Pittsburgh Medical Center

Mechanicsburg, Pennsylvania, 17050

United States

Einstein Medical Center Philadelphia

Philadelphia, Pennsylvania, 19141

United States

Texas Heart Institute

Houston, Texas, 77030

United States

The University of Vermont Medical Center

Burlington, Vermont, 05401

United States

Inova Health Care Services

Falls Church, Virginia, 22042

United States

Aurora Research Institute

Milwaukee, Wisconsin, 53215

United States

Collaborators and Investigators

Sponsor: REDNVIA Co., Ltd.

Jae K Oh, MD, PRINCIPAL_INVESTIGATOR, Mayo Clinic

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-06-27

Study Completion Date2026-12-30

Study Record Updates

Study Start Date2022-06-27

Study Completion Date2026-12-30

Terms related to this study

Additional Relevant MeSH Terms

Calcific Aortic Valve Disease