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)

Aldose Reductase Inhibition for Stabilization of Exercise capacity in Heart Failure (ARISE-HF): A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-001 in Patients with Diabetic Cardiomyopathy / Stage B Heart Failure at High Risk of Progression to Overt Heart Failure (Stage C Heart Failure) - ARISE-HF

Status

Active, not recruiting

Phases

Phase 2Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-002558-21-DE

Enrollment

675

Registered

2019-11-22

Start date

2020-08-31

Completion date

Unknown

Last updated

2024-03-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetic Cardiomyopathy (DbCM) / Stage B Heart Failure (SBHF) MedDRA version: 20.0 Level: PT Classification code 10012647 Term: Diabetic cardiomyopathy System Organ Class: 10007541 - Cardiac disorders

Interventions

Product Name: AT-001 Product Code: AT-001 Pharmaceutical Form: Capsule, hard INN or Proposed INN: Caficrestat CAS Number: 1355612-71-3 Current Sponsor code: AT-001 Other descriptive name: AT-001 Conc

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Type 2 Diabetes Mellitus (T2DM) 2. One of the following age-related criteria: • Age = 60 years OR • Age = 40 to = 45% AND - At least 1 of the following 5 abnormalities: o Absolute value of Global longitudinal strain (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 •NT-proBNP = 50 pg/mL • HsTnT = 6 ng/L 4. CPET demonstration of both, as confirmed by the CPET core lab: • Impaired functional capacity, i.e., Peak VO2 =65 years) yes F.1.3.1 Number of subjects for this age range 405

Exclusion criteria

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) 140 mmHg (systolic) or > 90 mmHg (diastolic) at screening, treated or untreated 13. History of multiple (at least 2) 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 (RAAS) 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 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 (including hepatitis B and C), endocrine, pulmonary, neurological, psychiatric, immunological (including HIV-AIDS), dermatological, or gastrointestinal diseases or active malignant tumor (except for non-melanoma skin cancer) as well as conditions that would impact the performance of a CPET 23. Any other condition that prevents the obtainment of a good quality echocardiogram at baseline 24. History of substance abuse including alcohol within 3 years (use of cannabinoids is not an exclusion criterion) 25. History of clinically significant drug hypersensitivity reactions 26. Severe lower extremity complications and/or history of nontraumatic 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 the opinion of the Investigator, precludes the patient from following and completing the protocol 30. Use of

Design outcomes

Primary

Measure	Time frame
Main Objective: To demonstrate that AT-001 compared with placebo decreases the worsening of performance on a cardiopulmonary exercise test (CPET) in patients with Diabetic Cardiomyopathy (DbCM) / Stage B Heart Failure (SBHF) ;Secondary Objective: To evaluate: • the efficacy of AT-001 compared with placebo in preventing progression from SBHF to Stage C Heart Failure • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the levels of NT-proBNP • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the score of the mKCCQ • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the percentage of patients with any changes and clinically significant changes (>6%) in peak oxygen uptake • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the significant worsening of DbCM from baseline • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the changes in systolic function assessed by global longitudinal strain, left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction assessed by E/E, and right ventricular systolic pressure by echocardiography • the safety of chronic administration of AT-001 to patients with DbCM/SBHF;Primary end point(s): Changes in CPET performance (peak oxygen uptake [peak VO2]) from baseline to Month 15 (>=15 months and = 18 months after randomization) and possibly to Month 27 (>= 27 months and = 30 months after randomization);Timepoint(s) of evaluation of this end point: Baseline to Month 15 (>=15 months and = 18 months after randomization) and possibly to Month 27 (>= 27 months and = 30 months after randomization)	—

Measure

Time frame

Main Objective: To demonstrate that AT-001 compared with placebo decreases the worsening of performance on a cardiopulmonary exercise test (CPET) in patients with Diabetic Cardiomyopathy (DbCM) / Stage B Heart Failure (SBHF) ;Secondary Objective: To evaluate: • the efficacy of AT-001 compared with placebo in preventing progression from SBHF to Stage C Heart Failure • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the levels of NT-proBNP • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the score of the mKCCQ • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the percentage of patients with any changes and clinically significant changes (>6%) in peak oxygen uptake • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the significant worsening of DbCM from baseline • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the changes in systolic function assessed by global longitudinal strain, left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction assessed by E/E, and right ventricular systolic pressure by echocardiography • the safety of chronic administration of AT-001 to patients with DbCM/SBHF;Primary end point(s): Changes in CPET performance (peak oxygen uptake [peak VO2]) from baseline to Month 15 (>=15 months and = 18 months after randomization) and possibly to Month 27 (>= 27 months and = 30 months after randomization);Timepoint(s) of evaluation of this end point: Baseline to Month 15 (>=15 months and = 18 months after randomization) and possibly to Month 27 (>= 27 months and = 30 months after randomization)

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Secondary

Measure	Time frame
Secondary end point(s): • Progression to SCHF, defined by the occurrence of at least 1 of the following events by Month 27: o CV death o Hospitalization for HF o Urgent HF visit o New diagnosis of HF (requiring initiation of a loop diuretic) • Changes in NT-proBNP • Changes in the mKCCQ score • Percentage of patients with a clinically significant decrease in peak VO2 (i.e., > 6%) ;Timepoint(s) of evaluation of this end point: Baseline to Month 27	—

Measure

Time frame

Secondary end point(s): • Progression to SCHF, defined by the occurrence of at least 1 of the following events by Month 27: o CV death o Hospitalization for HF o Urgent HF visit o New diagnosis of HF (requiring initiation of a loop diuretic) • Changes in NT-proBNP • Changes in the mKCCQ score • Percentage of patients with a clinically significant decrease in peak VO2 (i.e., > 6%) ;Timepoint(s) of evaluation of this end point: Baseline to Month 27

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Countries

Australia, Canada, Czechia, Czech Republic, France, Germany, Hong Kong, Poland, Spain, United Kingdom, United States

Contacts

Public ContactClinical Trials Information

Medpace

regsubmissions@medpace.com44(0)17460 400, ext. 24404

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026