A research study to evaluate the safety and efficacy of AT-001 in patients who may be at risk for a heart condition known as diabetic cardiomyopathy (DbCM) as a complication of a type 2 diabetes mellitus (T2DM)

Phase 1

• Conditions: Diabetic Cardiomyopathy (DbCM) / Stage B Heart Failure (SBHF); MedDRA version: 20.0Level: PTClassification code 10012647Term: Diabetic cardiomyopathySystem Organ Class: 10007541 - Cardiac disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2019-002558-21-CZ
• Lead Sponsor: Applied Therapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-02-12
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 675

Inclusion Criteria

1. Type 2 Diabetes Mellitus (T2DM)
2. One of the following age-related criteria:
• Age = 60 years OR
• Age = 40 to < 60 years AND at least 1 of the following 2 risk factors:
o Duration of diabetes = 10 years
o eGFR < 60 mL/min/1.73 m2
3. Demonstration of DbCM/ Stage B Heart Failure defined by at least one of the following 3 criteria:
• Echocardiographic demonstration of the following, as confirmed by either the central core lab or by local review at selected study centers:
- Left Ventricular Ejection Fraction (LVEF) >= 45%
AND
- At least 1 of the following 5 abnormalities:
o Absolute value of Global longitudinal strain (GLS) < 16% (i.e., GLS >-16%)
o Left ventricular hypertrophy (LVH) defined as left ventricular mass index (LVMI) = 95 g/m2 in women and =115 g/m2 in men
o Left atrial enlargement (LAE) defined as left atrial volume index (LAVi) = 34 mL/m2
o Diastolic Dysfunction defined as E/E’ = 13
o Right ventricular systolic pressure (RVSP) > 35 mmHg
OR
• NT-proBNP = 50 pg/mL
OR
• HsTnT = 6 ng/L
4. CPET demonstration of both, as confirmed by the CPET core lab:
• Impaired functional capacity, i.e., Peak VO2 < 75% of predicted, based on age and gender
• Ability of maximal effort, i.e., achieve a RER =1.05
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 405

Exclusion Criteria

1.Prior diagnosis of overt/symptomatic heart failure / stage C heart failure (SCHF), or prior or current symptom(s) or sign(s) that in the
opinion of the investigator may be related to undiagnosed overt/symptomatic heart failure / SCHF.
2. Any prior echocardiographic measurement indicating ejection fraction (EF) < 40%
3. History of acute coronary syndrome (ACS), including acute myocardial infarction
4. History or planned coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI; e.g., stent or angioplasty)
5. Prior diagnosis of coronary artery disease (CAD) defined as = 50% stenosis of any major coronary artery
6. History of severe mitral, aortic, tricuspid, or pulmonary valve disease, or moderate valve disease requiring intervention
7. History of any clinically significant arrhythmia (including permanent atrial fibrillation or history of paroxysmal atrial fibrillation requiring hospitalization, unless successfully ablated with no episodes of recurrence for at least 3 years)
8. History of stroke
9. History of congenital, infective, toxic (e.g., chemotherapy or radiation), infiltrative (e.g., amyloidosis, sarcoidosis, or hemochromatosis), post-partum, or hypertrophic cardiomyopathy
10. Myocarditis induced by active autoimmune disease (e.g., Graves’ disease or systemic lupus erythematosus)
11. Pulmonary arterial hypertension
12. Blood pressure > 140 mmHg (systolic) or > 90 mmHg (diastolic) at screening, treated or untreated
13. History of multiple hospitalizations for hypertensive emergency
14. BMI > = 45 kg/m2
15. Antihyperglycemic treatment has not been stable in the 12 weeks prior to screening in the opinion of the Investigator
16. Treatment with inhibitors of the renin-angiotensin-aldosterone system has not been stable in the 12 weeks prior to screening in the opinion of the Investigator
17. Use of thiazolidinediones at screening and/or after randomization
18. Planned start of a SGLT2-inhibitor after randomization (If a decision to start a SGLT2-inhibitor has already been made during the screening
period, the treatment with a SGLT2-inhibitor should be initiated before randomization. Note that initiation of a SGLT2-inhibitor during the study
is allowed at any time before and after randomization.)
19. Any current or prior use of a loop diuretic
20. Pregnant or breastfeeding women
21. Females of childbearing potential not willing to use a highly effective form of birth control from screening until the Study Closeout Visit, or Post-Treatment Follow-up Visit, whichever occurs later
22. Severe disease making implementation of the protocol or interpretation of the study results difficult . This includes clinically significant hematopoietic, renal, hepatic, endocrine, pulmonary, neurological, psychiatric, immunological, dermatological, or gastrointestinal diseases or active malignant tumor as well as conditions that would impact the performance of a CPET.
23. Any condition that prevents the obtainment of a good quality echocardiogram at baseline
24. History of substance abuse including alcohol within 3 years
25. History of clinically significant drug hypersensitivity reactions
26. Severe lower extremity complications and/or history of non-traumatic amputations
27. Short life expectancy (<12 months) making implementation of the protocol or interpretation of the study results difficult.
28. Investigators, site personnel directly affiliated with this study, and their immediate families
29. Any other condition that, in

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified