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)

NCT05143177 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: TR-CAVD-001
• Study Type: interventional
• Target: 580
• Locations: 2 countries
• Sites: 25

Brief Summary

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.

Conditions

Calcific Aortic Valve Disease

Outcome Measures

Primary Outcomes (1)

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

  at 104 weeks

Secondary Outcomes (3)

• Change in aortic stenosis severity as measured by mean pressure gradient using echocardiography at week104 as compared to baseline

  at week104

• Change in aortic stenosis severity as measured by aortic valve area (AVA) using echocardiography at week 104 as compared to baseline

  at week104

• Time-to-AV intervention to treat aortic stenosis including AV replacement

  at week104

Other Outcomes (10)

• Time-to-major adverse cardiovascular events of cardiac death, non- fatal myocardial infarction, heart failure hospitalization and stroke

  at week 104 as compared to baseline

• Time-to-symptom onset

  at week 104

• Aortic valve calcification as measured by change from baseline change from baseline in Arbitrary Units (-AU) by the Agatston method using cardiac computed tomography (CT) at week 52

  at week 52

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

DA-1229 10 mg

ACTIVE COMPARATOR

Drug: Evogliptin

Interventions

Evogliptin DRUG

DA-1229 10 mg, 1 tab

Also known as: DA-1229

DA-1229 10 mg

Placebo DRUG

DA-1229 Placebo, 1 tab

Placebo

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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 Type 1 diabetes mellitus.
• Subject has a history of diabetic ketoacidosis (DKA).
• Subject has a history of severe hypoglycemia (blood glucose levels \< 54 mg/dl) within the previous six months prior to screening.
• Note: Subjects receiving treatment for their non-type 1 diabetes and without history of DKA or severe hypoglycemia episode in the preceding 6 months who are interested in participating in the trial are recommended to inform/consult their diabetes provider prior to enrollment in the study or IP initiation to discuss if adjustment in their diabetes therapy or other monitoring may be needed.
• 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
• Subjects who are currently taking or anticipated to take any of the following medications for the duration of the study:

Sponsors & Collaborators

• REDNVIA Co., Ltd.: lead

Study Sites (25)

Mayo Clinic, AZ

Phoenix, Arizona, 85054, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Mayo Clinic, FL

Jacksonville, Florida, 32224, United States

Location

Baycare Health systems

Safety Harbor, Florida, 34695, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Beaumont Hospital, Royal Oak

Royal Oak, Michigan, 48073, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

Location

Rutgers- Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

Ichan School of Medicine

New York, New York, 10025, United States

Location

Stony brook

Stony Brook, New York, 11974, United States

Location

Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

OhioHealth Research Institute

Columbus, Ohio, 43214, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center

Mechanicsburg, Pennsylvania, 17050, United States

Location

Einstein Medical Center Philadelphia

Philadelphia, Pennsylvania, 19141, United States

Location

Texas Heart Institute

Houston, Texas, 77030, United States

Location

The University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Inova Health Care Services

Falls Church, Virginia, 22042, United States

Location

Aurora Research Institute

Milwaukee, Wisconsin, 53215, United States

Location

Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval

Québec, Canada

Location

MeSH Terms

Interventions

4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one

Study Officials

• Jae K Oh, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2021
• First Posted: December 3, 2021
• Study Start: June 27, 2022
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 27, 2026

Record last verified: 2025-06

Locations

US (24); CA (1)