Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy Clinical Trial Results and Information

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

ClinicalTrials.gov processed this data on December 7, 2022. Link to the current ClinicalTrials.gov record.

Recruitment Status

ACTIVE, NOT RECRUITING (See Contacts and Locations)
Verified December 2022 by Applied Therapeutics, Inc.

Sponsor

Applied Therapeutics, Inc.

Information Provided by (Responsible Party)

Applied Therapeutics, Inc.

Clinicaltrials.gov Identifier

NCT04083339
Other Study ID Numbers: AT-001-2001
First Submitted: August 23, 2019
First Posted: September 10, 2019
Last Update Posted: December 8, 2022
Last Verified: December 2022
History of Changes

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Tracking Information
First Submitted Date	August 23, 2019
First Posted Date	September 10, 2019
Last Update Posted Date	December 8, 2022
Study Start Date	September 20, 2019
Anticipated Primary Completion Date	December 2023
Current Primary Outcome Measures (submitted: December 7, 2022)	Peak VO2 during cardio-pulmonary exercise test (CPET); [15 months after randomization]] 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).
Change History	Complete list of historical versions of study NCT04083339 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures	Progression to overt heart failure (Stage C Heart Failure) [27 months after randomization] 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 Changes in NT-proBNP [27 months after randomization] Changes in NT-proBNP may reflect worsening of cardiomyopathy over time Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score [27 months after randomization] Changes in the modified KCCQ may reflect deterioration of clinical status over time
Current Other Outcome Measures	Worsening of diabetic cardiomyopathy [15 and 27 months after randomization] Defined by either ≥ 20% increase in NT-proBNP or ≥ 5 point decrease in the mKCCQ score Changes in echocardiographic parameters [27 months after randomization] Changes assessed on cardiac ultra-sound from baseline

Descriptive Information
Brief Title	Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
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
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.
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.
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized Interventional Model: Parallel Assignment Masking: Quadruple Primary Purpose: Treatment
Target Follow-Up Duration	Not Provided
Biospecimen	Not Provided
Sampling Method	Not Provided
Study Population	Not Provided
Condition	Diabetic Cardiomyopathies
Intervention	Drug: AT-001 AT-001 will be administered as 3 capsules twice daily, before breakfast and before dinner. At present AT001 is the sole name for the active substance. No INN/genetic name is available to date
Study Groups/Cohorts	Experimental: AT-001 High dose 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). Intervention: Drug: AT-001 Experimental: AT-001 Low Dose 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). Intervention: Drug: AT-001 Placebo Comparator: Placebo Comparator Placebo capsules will be used as comparator Intervention: Drug: Placebo
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status	Active, not recruiting
Anticipated Enrollment (submitted: December 7, 2022)	675
Anticipated Study Completion Date	December 2025
Anticipated Primary Study Completion Date	December 2023
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
Sex/Gender	Sexes Eligible for Study: All
Ages	40 Years and Older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries	United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, Australia, Australia, Australia, Australia, Australia, Australia, Australia, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Czechia, Czechia, Czechia, France, France, France, France, Germany, Germany, Germany, Germany, Germany, Hong Kong, Hong Kong, Poland, Poland, Poland, Poland, Poland, Poland, Poland, Poland, Poland, Spain, Spain, Spain, Spain, Spain, Spain, Spain, United Kingdom, United Kingdom, United Kingdom, United Kingdom, United Kingdom

Administrative Information
NCT Number	NCT04083339
Other Study ID Numbers	AT-001-2001
Has Data Monitoring Committee	Not Provided
U.S FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Product Manufactured in and Exported from the U.S.: Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Applied Therapeutics, Inc., Applied Therapeutics, Inc.
Study Sponsor	Applied Therapeutics, Inc.
Collaborators	Not Provided
Investigators
PRS Account	Applied Therapeutics, Inc.
Verification Date	December 2022