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)

Plain English Summary

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) is a Phase 3 clinical trial sponsored by REDNVIA Co., Ltd. studying Calcific Aortic Valve Disease. Tests DA-1229 (Evogliptin) for calcific aortic valve disease with mild to moderate aortic stenosis. For adults aged 35+ with calcific aortic valve disease and mild to moderate aortic stenosis. Participation involves taking DA-1229 or placebo daily for 104 weeks. Alternatives include standard medical care and other clinical trials. The trial aims to enroll 580 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if aged 35+ with calcific aortic valve disease and mild to moderate aortic stenosis. Not eligible if have severe aortic valve regurgitation, severe mitral or tricuspid valve disease, or NYHA class III/IV heart failure. Must be able to undergo cardiac CT and have a life expectancy of at least 2 years. Must not have severe allergic reactions to DPP4 inhibitors. This trial is studying Calcific Aortic Valve Disease, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the change in aortic valve calcification, which means it tracks how much the disease progresses or improves over time. The specific primary outcome measures are: 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). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill the gap in treatment options for calcific aortic valve disease by evaluating the efficacy and safety of DA-1229. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Calcific Aortic Valve Disease, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape suggest a high approval probability for DA-1229 if successful. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 580 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have calcific aortic valve disease and mild to moderate aortic stenosis. Participation involves taking DA-1229 or placebo daily for 104 weeks. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 580 participants

Interventions

• DRUG: Evogliptin — DA-1229 10 mg, 1 tab
• DRUG: Placebo — DA-1229 Placebo, 1 tab

Primary Outcomes

• 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

• 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)

Full Eligibility Criteria

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 (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.

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 Type 1 diabetes mellitus.
11. Subject has a history of diabetic ketoacidosis (DKA).
12. 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.
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:

    oDPP4 inhibitor other than the investigational product

    ▪Subjects taking insulin or sulfonylureas should consult their primary diabetes provider prior to enrollment in the study or IP initiation to discuss if adjustment in their diabetes therapy and/or other monitoring may be needed.

    oVitamin K

    ▪Subjects taking over-the-counter multivitamins containing ≤ 90 mcg/day vitamin K will be allowed to continue use during the study.

    oChronic use of any medications that strongly impact hepatic metabolism by way of inducing or inhibiting the CYP3A4 system, giving rise to drug-drug interaction (with the exception of focal or limited topical treatment)
    * Strong CYP3A4 inducers\* including but not limited to 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).
    * 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.

    oNote: Alcohol abuse is a pattern of drinking that results 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 probl

Trial Locations

• Mayo Clinic, AZ, Phoenix, Arizona, United States
• University of Southern California, Los Angeles, California, United States
• University of Colorado, Aurora, Colorado, United States
• Mayo Clinic, FL, Jacksonville, Florida, United States
• Baycare Health systems, Safety Harbor, Florida, United States
• Northside Hospital, Atlanta, Georgia, United States
• Massachusetts General Hospital, Boston, Massachusetts, United States
• University of Michigan, Ann Arbor, Michigan, United States
• Henry Ford Health System, Detroit, Michigan, United States
• Beaumont Hospital, Royal Oak, Royal Oak, Michigan, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Calcific aortic valve disease, aortic stenosis, heart valve disorders, cardiovascular diseases

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