Evogliptin for Aortic Stenosis

Recruiting at 36 trial locations

Overseen By Nima Sabbaghian, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: REDNVIA Co., Ltd.

Must not be taking: DPP4 inhibitors, Vitamin K, CYP3A4 drugs

Disqualifiers: Severe valve disease, Heart failure, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

580 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of Evogliptin for individuals with calcific aortic valve disease, which narrows the heart's aortic valve. Participants will be divided into two groups: one receiving Evogliptin and the other a placebo (a non-active pill). The trial is ideal for adults diagnosed with mild to moderate aortic stenosis who can participate for the study's full duration. As a Phase 2 trial, this research measures how well Evogliptin works in an initial, smaller group, offering participants an opportunity to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as other DPP4 inhibitors, strong CYP3A4 inducers or inhibitors, and Vitamin K supplements above a certain dose. If you are on insulin or sulfonylureas, you should consult your diabetes provider to discuss any necessary adjustments.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that evogliptin, also known as DA-1229, has undergone safety testing in individuals with aortic valve issues. Studies found that after 96 weeks, patients taking evogliptin experienced similar changes in their aortic valve condition as those taking a placebo, indicating that evogliptin is generally well-tolerated over time.

These studies reported no major side effects, suggesting that serious side effects were rare. This finding reassures prospective trial participants, as it suggests the treatment is generally safe. However, as with any treatment, staying informed and discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for aortic stenosis?

Unlike the standard of care for aortic stenosis, which typically involves surgical valve replacement or repair, Evogliptin offers a novel approach by targeting the metabolic pathways linked to heart valve disease. Researchers are excited about Evogliptin because it is a DPP-4 inhibitor, a class of drugs primarily used for diabetes, which may help improve heart valve function without surgery. This innovative mechanism of action sets it apart from traditional treatments and could provide a less invasive option for patients with aortic stenosis.

What evidence suggests that this trial's treatments could be effective for aortic stenosis?

Research has shown that evogliptin might help with aortic stenosis, a condition where the heart's aortic valve narrows. Some studies suggest that evogliptin can slow the disease by reducing swelling and thickening of the valve tissue. However, other studies found it did not significantly affect the valve's narrowing. These mixed results indicate potential, but more research is needed to confirm its effectiveness for aortic stenosis. In this trial, participants will receive either evogliptin or a placebo to further investigate its effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Jae K Oh, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults over 35 with mild to moderate calcific aortic valve disease and stenosis, who can undergo heart CT scans and agree to study procedures. Excludes those with diabetes, pancreatitis, severe heart or kidney conditions, life expectancy under 2 years, recent severe cardiovascular events, drug non-compliance history, pregnancy or breastfeeding women not using contraception.

Inclusion Criteria

Subject understands and agrees to comply with planned study procedures

I am 35 years old or older.

I have mild to moderate aortic stenosis confirmed by heart scans.

Exclusion Criteria

I have moderate or severe leakage in my aortic heart valve.

Your liver enzymes (ALT and AST) are more than 2.5 times the normal range.

Pregnant or lactating women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive DA-1229 or placebo orally once daily

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Evogliptin
• Placebo

Trial Overview The trial is testing the safety and effectiveness of Evogliptin (DA-1229) in patients with aortic valve disease. Participants are randomly assigned to receive either Evogliptin at two different doses (5mg or 10mg) or a placebo daily for 104 weeks.

How Is the Trial Designed?

Group I: DA-1229 10 mg Active Control 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

REDNVIA Co., Ltd.

Lead Sponsor

Trials

2

Recruited

1,100+

Published Research Related to This Trial

In a study of 20 hypertensive patients with aortic valve stenosis, ACE inhibitors significantly lowered systolic blood pressure and improved stroke volume during peak stress, indicating a positive effect on stress haemodynamics.

Despite these benefits, ACE inhibitors also led to an increased mean pressure gradient, suggesting that their afterload relief effect is countered in patients with aortic stenosis, but they should still be continued due to their overall favorable impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of angiotensin converting enzyme inhibitors in hypertensive patients with aortic valve stenosis: a drug withdrawal study. Jiménez-Candil, J., Bermejo, J., Yotti, R., et al.[2018]

Currently, there is no medical therapy to slow the progression of aortic stenosis, which affects about 6% of the elderly population, but emerging treatments targeting low-density lipoprotein (LDL) and lipoprotein(a) (Lp(a)) levels show promise.

New therapies like PCSK9 inhibitors and antisense oligonucleotides (ASO) are being tested, with some reducing Lp(a) levels by 85-90%, and ongoing Phase 3 studies aim to evaluate their impact on cardiovascular events in patients with elevated Lp(a) and cardiovascular diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lp(a) in the Pathogenesis of Aortic Stenosis and Approach to Therapy with Antisense Oligonucleotides or Short Interfering RNA. Di Costanzo, A., Indolfi, C., Franzone, A., et al.[2023]

Aortic valve replacement is currently the only treatment proven to improve survival in patients with severe symptomatic aortic stenosis, highlighting the urgency of addressing this condition before symptoms develop.

The review discusses various medical therapies, including lipid-lowering and antihypertensive drugs, which may help slow the progression of aortic stenosis and improve heart function, although more research is needed to confirm their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical Treatment of Aortic Stenosis. Marquis-Gravel, G., Redfors, B., Leon, MB., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7824080/

Evogliptin Suppresses Calcific Aortic Valve Disease by ... Evogliptin suppresses calcific aortic valve disease by attenuating inflammation, fibrosis, and calcification.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05143177

NCT05143177 | A Study to Evaluate the Efficacy and ... 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).

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39260927/

Effect of Evogliptin on the Progression of Aortic Valvular ... This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0735109724078896

Effect of Evogliptin on the Progression of Aortic Valvular ... We demonstrate that treatment with evogliptin had no significant effect on the progression of AV calcification over 96 weeks in asymptomatic patients with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05143177?term=NCT05143177&rank=1

A Study to Evaluate the Efficacy and Safety of DA-1229 ... 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).

6. jacc.org jacc.org/doi/abs/10.1016/j.jacc.2024.06.037

Effect of Evogliptin on the Progression of Aortic Valvular ... In the placebo group, the increase in AVCV between 48 weeks and 96 weeks was higher than that between baseline and 48 weeks (136 mm3; 95% CI: 108–163 vs 102 mm3 ...