A Study to Evaluate the Effectiveness and Safety of DA-1229 (Evogliptin) in Delaying Progression of Mild or Moderate Calcific Aortic Stenosis (EVOID-AS trial)

Overview

About this study

The purpose of this study is to evaluate the effectiveness 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 Group, 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 is 112 Weeks.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 2/8/23. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Ratnasari Padang, M.B.B.S., Ph.D.

Open for enrollment

Contact information:

RST EVOID-AS Study Team

(507) 266-9861

RSTEVOID@mayo.edu

Jacksonville, Fla.

Mayo Clinic principal investigator

Peter Pollak, M.D.

Open for enrollment

Contact information:

Erika Douglass M.P.H.

(904) 953-6595

Douglass.Erika@mayo.edu

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Tasneem Naqvi, M.B.B.S., M.D.

Open for enrollment

Contact information:

Aatikah Mouti M.S.

(480) 342-2479

Mouti.Aatikah@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20539465

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