AT-001 for Diabetic Cardiomyopathy

Not currently recruiting at 93 trial locations

Overseen By Alessia Urbinati

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Applied Therapeutics, Inc.

Disqualifiers: Heart failure, Coronary disease, Arrhythmia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of a new drug, AT-001, for individuals with diabetic cardiomyopathy, a heart condition linked to type 2 diabetes that can lead to heart failure. The study will compare different doses of AT-001 with a placebo (a pill with no active medicine) to determine which is most effective at slowing or stopping the progression of the condition. Individuals with type 2 diabetes and diabetic cardiomyopathy who have not yet developed severe heart failure might be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Studies have shown that AT-001 is generally safe for people with diabetic heart disease. In earlier research, patients took both high and low doses of AT-001, and these studies did not find any major safety issues. Common side effects were mild, such as headaches and nausea. The current testing of AT-001 in a later phase of trials indicates some confidence in its safety for humans. However, discussing any concerns with a doctor before joining a trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for diabetic cardiomyopathy?

Unlike the standard treatments for diabetic cardiomyopathy, which mainly focus on controlling blood sugar levels or managing heart failure symptoms, AT-001 targets a novel pathway by inhibiting the production of sorbitol. Sorbitol is a sugar alcohol that accumulates in cells and can lead to cellular damage, so reducing its production is a fresh approach to treating this condition. Researchers are particularly excited about AT-001 because of its potential to directly address the underlying metabolic issue contributing to heart problems in diabetics, offering a more targeted and possibly more effective treatment compared to current options.

What evidence suggests that this trial's treatments could be effective for Diabetic Cardiomyopathy?

Research shows that AT-001, which participants in this trial may receive, blocks an enzyme called aldose reductase. This enzyme can cause a build-up of sorbitol, a sugar alcohol that can harm cells. Studies have found that AT-001 significantly reduces sorbitol levels in the blood, potentially protecting the heart in people with diabetic cardiomyopathy, a heart disease caused by diabetes. In earlier trials, patients taking AT-001 maintained their ability to exercise, suggesting it might improve heart function. Although some results showed no major improvement in exercise ability over 15 months, the treatment was well-tolerated with no serious side effects. These findings suggest that AT-001 could help manage heart issues related to diabetes by targeting this specific enzyme. ^{2 3 4 5 6}

Who Is on the Research Team?

James L Januzzi, MD

Principal Investigator

Harvard Medical School (HMS and HSDM)

Are You a Good Fit for This Trial?

This trial is for adults with Diabetic Cardiomyopathy who are at high risk of developing heart failure. Participants must have Type 2 Diabetes and reduced exercise capacity (Peak VO2 < 75% of normal). They can't join if they've had severe heart issues, uncontrolled blood pressure, or a history of significant cardiac events.

Inclusion Criteria

I have Type 2 Diabetes.

My exercise capacity is less than 75% of what's expected for my age and gender.

I have heart problems related to diabetes.

Exclusion Criteria

I need treatment for a serious heart valve problem.

I have a serious irregular heartbeat.

Your blood pressure is higher than 140 over 90 at the initial check-up.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A - Treatment

Evaluation of the safety and efficacy of two doses of AT-001 vs placebo to improve or prevent the decline of functional capacity in patients with Diabetic Cardiomyopathy

15-18 months

Part B - Extension

Extension phase to evaluate the safety and efficacy of chronic administration of AT-001 vs placebo, including safety endpoints and exploratory clinical efficacy endpoints

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AT-001
• Placebo

Trial Overview The study tests the safety and effectiveness of AT-001 against a placebo in managing Diabetic Cardiomyopathy to prevent worsening into overt heart failure. It's conducted across multiple centers where participants are randomly assigned to either the drug or placebo group.

How Is the Trial Designed?

Group I: AT-001 Low Dose Experimental Treatment 1 Intervention

The total daily doses will be of 2g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 2g/day of AT-001 is capable of producing a sufficient inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity).

Group II: AT-001 High dose Experimental Treatment 1 Intervention

The total daily doses will be of 3g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 3g/day of AT-001 is capable of producing the maximum inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity).

Group III: Placebo Comparator Placebo Group 1 Intervention

Placebo capsules will be used as comparator

Who Is Running the Clinical Trial?

Applied Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

900+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38597864/

Randomized Trial of a Selective Aldose Reductase ... Among individuals with DbCM and impaired exercise capacity, treatment with AT-001 for 15 months did not result in significantly better ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04083339

NCT04083339 | Safety and Efficacy of AT-001 in Patients ... The primary objective of Part A is to demonstrate that AT-001 improves or prevents the decline of functional capacity in patients with Diabetic Cardiomyopathy.

3. appliedtherapeutics.com appliedtherapeutics.com/wp-content/uploads/2019/11/Final_Applied-Therapeutics-AHA-2019-poster_RP_AG_SS.pdf

Clinical Assessment of AT-001, an Aldose Reductase ... AT-001 potently inhibited AR, resulting in significant reduction in blood sorbitol levels, sustained over 28 days. AT-001 was well tolerated with no SAEs and ...

4. ahajournals.org ahajournals.org/doi/10.1161/circ.140.suppl_1.13475

Abstract 13475: Clinical Assessment of AT-001, an Aldose ... Results: T2DM adult patients (age 18-75, HbA1c 5.0-8.5%) with early DbCM were treated with AT-001, a novel potent ARI, for 28 days in a Phase 2 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0735109724066130

Randomized Trial of a Selective Aldose Reductase ... This study sought to determine whether AT-001, a highly selective aldose reductase inhibitor, can stabilize exercise capacity among individuals with diabetic ...

6. caymanchem.com caymanchem.com/product/36105/at-001?srsltid=AfmBOor1tYd6ECF2HjDjkDJl_OgvHHg2wG0Y-33hvT2l--4mAhzXI08B

AT-001 (Caficrestat, CAS Number: 1355612-71-3) AT-001 is an inhibitor of aldose reductase (IC50 = 28.9 pM). It reduces infarct area in streptozotocin-induced diabetic mice expressing human aldose ...