Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy

Diabetic Cardiomyopathies Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04083339
• Other study ID #: AT-001-2001
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 20, 2019
• Est. completion date: December 2025

Study information

• Verified date: December 2022
• Source: Applied Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 675
• Est. completion date: December 2025
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• 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
• Placebo
Matching placebo will be administered as 3 capsules twice daily, before breakfast and before dinner

Locations

Country	Name	City	State
Australia	Prince Charles Hospital	Chermside	Queensland
Australia	Barwon Health-University Hospital Geelong	Geelong	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	University of Tasmania at Hobart	Hobart	Tasmania
Australia	Baker Heart and Diabetes Institute	Melbourne	Victoria
Australia	CORE Research Group Pty. Ltd.	Milton	Queensland
Australia	AusTrials	Taringa	Queensland
Canada	LMC Diabetes & Endocrinology Ltd. - Brampton	Brampton	Ontario
Canada	C-Endo - Endocrinology Centre	Calgary	Alberta
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	LMC Diabetes & Endocrinology Ltd. - Thornhill	Concord	Ontario
Canada	LMC Diabetes & Endocrinology Ltd. - Etobicoke	Etobicoke	Ontario
Canada	Centre for Studies in Family Medicine, Western Centre for Public Health and Family Medicine, Western University	London	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie De Quebec	Québec	Quebec
Canada	LMC Diabetes & Endocrinology Ltd. - Toronto	Toronto	Ontario
Canada	BC Diabetes	Vancouver	British Columbia
Czechia	Edumed s.r.o.	Jaromer
Czechia	Nemocnice Pardubickeho kraje, a.s., Nemocnice Pardubice	Pardubice
Czechia	Vseobecna fakultni nemocnice v Praze	Praha
France	Hôpital Jean-Verdier - AP-HP; Service Endocrinologie Diabétologie Nutrition	Bondy
France	CHU Henri Mondor	Créteil
France	CHU de Nantes, Clinique d'Endocrinologie	Nantes
France	Centre Hospitalier de Valenciennes	Valenciennes
Germany	Herz-und Diabeteszentrum NRW Universitaetsklinik der Ruhr-Universitaet Bochum	Bad Oeynhausen	North Rhine Westphalia
Germany	Klinische Forschung Berlin GbR	Berlin
Germany	Cardiologicum Pirna und Dresden	Dresden	Saxony
Germany	ZKS - Zentrum Klinische Studien Sudbrandenburg GmbH	Elsterwerda
Germany	Klinikum Frankfurt (Oder) GmbH	Frankfurt (Oder)	Brandenburg
Hong Kong	Erik Yee Mun George Fung	Sha Tin
Hong Kong	Prince of Wales Hospital; Chinese University of Hong Kong; Dept of Medicine and Therapeutics	Sha Tin
Poland	NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny	Bialystok
Poland	Centrum Twojego Zdrowia	Kraków
Poland	Topolowa MEDICENTER Mrózek & wspólnicy sp.j.	Kraków
Poland	ETG Lodz	Lódz
Poland	Praktyka Lekarska Ewa Krzyzagorska	Poznan
Poland	Prywatny Gabinet Lekarski Centrum Medyczne Diabetika	Radom
Poland	Centrum Medyczne Medyk Stanislaw Mazur Sp. z o.o. SK	Rzeszów
Poland	4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu	Wroclaw
Poland	Centrum Chorob Serca w USK	Wroclaw	Borowska
Spain	Hospital Abente y Lago (Complejo Universitario de la Coruña)	A Coruña
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau Barcelona	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Clinico Universitario Virgen de la Arrixaca	El Palmar	Murcia
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
United Kingdom	Ninewells Hospital & Medical School	Dundee
United Kingdom	CPS Research	Glasgow
United Kingdom	Glenfield hospital	Leicester
United Kingdom	Barts and The London School of Medicine & Dentistry	London
United Kingdom	Wythenshawe Hospital	Manchester
United States	Westside Medical Associates of Los Angeles	Beverly Hills	California
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Chear Center LLC	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	Cleveland Clinic	Cleveland	Ohio
United States	Remington Davis, Inc.	Columbus	Ohio
United States	ALL Medical Research, LLC	Cooper City	Florida
United States	Dallas Diabetes Research Center	Dallas	Texas
United States	Southwest Family Medicine Associates	Dallas	Texas
United States	University of Texas Southwestern	Dallas	Texas
United States	Mountain View Clinical Research	Greer	South Carolina
United States	Mountain View Clinical Research - Greer	Greer	South Carolina
United States	New Generation of Medical Research	Hialeah	Florida
United States	Juno Research, LLC - Northwest Site	Houston	Texas
United States	Juno Research, LLC - Southwest Houston Site	Houston	Texas
United States	Universty of Mississippi Medical Center	Jackson	Mississippi
United States	Holston Medical Group	Kingsport	Tennessee
United States	University of California, San Diego (UCSD)	La Jolla	California
United States	FMC Science	Lampasas	Texas
United States	Clinical Trials Research	Lincoln	California
United States	South Oklahoma Heart Research	Oklahoma City	Oklahoma
United States	University of California - Irvine Medical Center	Orange	California
United States	Broward Research Center	Pembroke Pines	Florida
United States	UnityPoint Health - Methodist Hospital	Peoria	Illinois
United States	Progressive Medical Research	Port Orange	Florida
United States	St. Louis Heart and Vascular Cardiology	Saint Louis	Missouri
United States	Metabolic Institute of America	Tarzana	California
United States	Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Applied Therapeutics, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Worsening of diabetic cardiomyopathy	Defined by either = 20% increase in NT-proBNP or = 5 point decrease in the mKCCQ score	15 and 27 months after randomization
Other	Changes in echocardiographic parameters	Changes assessed on cardiac ultra-sound from baseline	27 months after randomization
Primary	Peak VO2 during cardio-pulmonary exercise test (CPET);	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).	15 months after randomization]
Secondary	Progression to overt heart failure (Stage C Heart Failure)	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	27 months after randomization
Secondary	Changes in NT-proBNP	Changes in NT-proBNP may reflect worsening of cardiomyopathy over time	27 months after randomization
Secondary	Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score	Changes in the modified KCCQ may reflect deterioration of clinical status over time	27 months after randomization