Evogliptin for Aortic Stenosis

Recruiting at 32 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

867 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an adaptive Phase 2/3 multicenter, double-blind, placebo-controlled, randomized, parallel, 3 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 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 GroupDA-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.

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.

What data supports the effectiveness of the drug Evogliptin for treating aortic stenosis?

Research shows that Evogliptin, a drug that inhibits DPP-4, can reduce inflammation, fibrosis (thickening and scarring of tissue), and calcification (hardening due to calcium deposits) in animal models of aortic stenosis. This suggests it might help slow the progression of this heart valve disease. ^{1 2 3 4 5}

How does the drug Evogliptin differ from other treatments for aortic stenosis?

Evogliptin is unique because it targets the inflammation, fibrosis, and calcification processes in aortic stenosis by inhibiting dipeptidyl peptidase-4 (DPP-4), which is not a focus of other treatments. This drug specifically accumulates in cardiac tissue, potentially offering a novel approach to slowing the progression of the disease, unlike current treatments that primarily involve surgical valve replacement. ^{1 2 6 7 8}

Research Team

Jae K Oh, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: DA-1229 5mg Active Control 1 Intervention

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

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

REDNVIA Co., Ltd.

Lead Sponsor

Trials

2

Recruited

1,100+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Dipeptidyl peptidase-4 inhibition to prevent progression of calcific aortic stenosis. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Evogliptin Suppresses Calcific Aortic Valve Disease by Attenuating Inflammation, Fibrosis, and Calcification. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Effects of angiotensin converting enzyme inhibitors in hypertensive patients with aortic valve stenosis: a drug withdrawal study. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Medical Treatment of Aortic Stenosis. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Lp(a) in the Pathogenesis of Aortic Stenosis and Approach to Therapy with Antisense Oligonucleotides or Short Interfering RNA. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Improvement of aortic valve stenosis by ApoA-I mimetic therapy is associated with decreased aortic root and valve remodelling in mice. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Longitudinal medical resources and costs among type 2 diabetes patients participating in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). [2019]

8. India pubmed.ncbi.nlm.nih.gov

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in aortic stenosis - Is this the light at the end of the tunnel for patients with aortic stenosis? [2021]