Brief Summary
This is a multicenter, randomized, placebo-controlled, 2-part study to evaluate the safety and efficacy of AT-001 in adult patients (N=675) with Diabetic Cardiomyopathy at high risk of progression to overt heart failure.
Brief Title
Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
Detailed Description
The study consists of two consecutive parts: Part A and Part B. Part A will evaluate the safety and efficacy of two doses of AT-001 vs placebo. 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. Part B is an extension of at least 12 months that will evaluate the safety and efficacy of chronic administration of AT-001 vs placebo in the same patients who had previously been evaluated in Part A. Assessments in Part B will include safety endpoints and exploratory clinical efficacy endpoints, i.e. death and hospitalization due to a cardiac event.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Diabetic Cardiomyopathies
Eligibility Criteria
Inclusion Criteria:
* Type 2 Diabetes Mellitus
* Diabetic cardiomyopathy
* Peak VO2 \< 75% of predicted normal value based on age and gender
Exclusion Criteria:
* Prior diagnosis or signs/symptoms of overt/symptomatic heart failure / stage C heart failure
* Prior echocardiogrphic measurement of ejection fraction (EF) \< 40%
* Prior acute coronary syndrome (ACS), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), coronary artery disease (CAD) or stroke
* Severe or moderate cardiac valve disease requiring intervention
* Clinically significant arrhythmia
* Prior diagnosis of congenital, infective, toxic, infiltrative, post-partum, or hypertrophic cardiomyopathy
* Blood pressure \> 140 mmHg (systolic) or \> 90 mmHg (diastolic) at screening
* HbA1c \>8.5% at screening
* Severe disease that would impact the performance of a cardio-pulmonary exercise test
* Type 2 Diabetes Mellitus
* Diabetic cardiomyopathy
* Peak VO2 \< 75% of predicted normal value based on age and gender
Exclusion Criteria:
* Prior diagnosis or signs/symptoms of overt/symptomatic heart failure / stage C heart failure
* Prior echocardiogrphic measurement of ejection fraction (EF) \< 40%
* Prior acute coronary syndrome (ACS), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), coronary artery disease (CAD) or stroke
* Severe or moderate cardiac valve disease requiring intervention
* Clinically significant arrhythmia
* Prior diagnosis of congenital, infective, toxic, infiltrative, post-partum, or hypertrophic cardiomyopathy
* Blood pressure \> 140 mmHg (systolic) or \> 90 mmHg (diastolic) at screening
* HbA1c \>8.5% at screening
* Severe disease that would impact the performance of a cardio-pulmonary exercise test
Inclusion Criteria
Inclusion Criteria:
* Type 2 Diabetes Mellitus
* Diabetic cardiomyopathy
* Peak VO2 \< 75% of predicted normal value based on age and gender
* Type 2 Diabetes Mellitus
* Diabetic cardiomyopathy
* Peak VO2 \< 75% of predicted normal value based on age and gender
Gender
All
Gender Based
false
Keywords
Type 2 Diabetes
Aldose Reductase Inhibitor
Stage B Heart Failure
Stage C Heart Failure
Cardiopulmonary Exercise Test
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
40 Years
NCT Id
NCT04083339
Org Class
Industry
Org Full Name
Applied Therapeutics, Inc.
Org Study Id
AT-001-2001
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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
Primary Outcomes
Outcome Description
Changes in Peak VO2 during cardio-pulmonary exercise test (CPET) from baseline to approximately Month 15 (15-18 months). A CPET may be repeated at approximately Month 27 (27-30 months).
Outcome Measure
Peak VO2 during cardio-pulmonary exercise test (CPET);
Outcome Time Frame
15 months after randomization]
Secondary Outcomes
Outcome Description
Defined by the occurrence of one of the following events: cardiovascular death, hospitalization for heart failure, urgent heart failure visit, new diagnosis of heart failure
Outcome Time Frame
27 months after randomization
Outcome Measure
Progression to overt heart failure (Stage C Heart Failure)
Outcome Description
Changes in NT-proBNP may reflect worsening of cardiomyopathy over time
Outcome Time Frame
27 months after randomization
Outcome Measure
Changes in NT-proBNP
Outcome Description
Changes in the modified KCCQ may reflect deterioration of clinical status over time
Outcome Time Frame
27 months after randomization
Outcome Measure
Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
40
Investigators
Investigator Type
Principal Investigator
Investigator Name
Leandro Slipczuk Bustamante
Investigator Email
lslipczukb@montefiore.org
Investigator Phone