Clinical trial NCT04083339: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Diabetic Cardiomyopathies
Keywords: Type 2 Diabetes
Aldose Reductase Inhibitor
Stage B Heart Failure
Stage C Heart Failure
Cardiopulmonary Exercise Test
Lead sponsor: Applied Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-09-10
Enrollment: 675
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Peak VO2 during cardio-pulmonary exercise test (CPET);
timeFrame: 15 months after randomization]
Secondary outcomes:
measure: Progression to overt heart failure (Stage C Heart Failure)
timeFrame: 27 months after randomization
measure: Changes in NT-proBNP
timeFrame: 27 months after randomization
measure: Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score
timeFrame: 27 months after randomization
Other outcomes:
measure: Worsening of diabetic cardiomyopathy
timeFrame: 15 and 27 months after randomization
measure: Changes in echocardiographic parameters
timeFrame: 27 months after randomization
Locations:
city: Beverly Hills
country: United States
facility: Westside Medical Associates of Los Angeles
state: California
city: La Jolla
country: United States
facility: University of California, San Diego (UCSD)
state: California
city: Lincoln
country: United States
facility: Clinical Trials Research
state: California
city: Orange
country: United States
facility: University of California - Irvine Medical Center
state: California
city: Tarzana
country: United States
facility: Metabolic Institute of America
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
state: California
city: Cooper City
country: United States
facility: ALL Medical Research, LLC
state: Florida
city: Hialeah
country: United States
facility: New Generation of Medical Research
state: Florida
city: Pembroke Pines
country: United States
facility: Broward Research Center
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Peoria
country: United States
facility: UnityPoint Health - Methodist Hospital
state: Illinois
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Jackson
country: United States
facility: Universty of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: St. Louis Heart and Vascular Cardiology
state: Missouri
city: Bronx
country: United States
facility: Chear Center LLC
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Remington Davis, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: South Oklahoma Heart Research
state: Oklahoma
city: Greer
country: United States
facility: Mountain View Clinical Research - Greer
state: South Carolina
city: Greer
country: United States
facility: Mountain View Clinical Research
state: South Carolina
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Dallas
country: United States
facility: Dallas Diabetes Research Center
state: Texas
city: Dallas
country: United States
facility: Southwest Family Medicine Associates
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Juno Research, LLC - Northwest Site
state: Texas
city: Houston
country: United States
facility: Juno Research, LLC - Southwest Houston Site
state: Texas
city: Lampasas
country: United States
facility: FMC Science
state: Texas
city: Chermside
country: Australia
facility: Prince Charles Hospital
state: Queensland
city: Milton
country: Australia
facility: CORE Research Group Pty. Ltd.
state: Queensland
city: Taringa
country: Australia
facility: AusTrials
state: Queensland
city: Hobart
country: Australia
facility: University of Tasmania at Hobart
state: Tasmania
city: Geelong
country: Australia
facility: Barwon Health-University Hospital Geelong
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Baker Heart and Diabetes Institute
state: Victoria
city: Calgary
country: Canada
facility: C-Endo - Endocrinology Centre
state: Alberta
city: Vancouver
country: Canada
facility: BC Diabetes
state: British Columbia
city: Brampton
country: Canada
facility: LMC Diabetes & Endocrinology Ltd. - Brampton
state: Ontario
city: Concord
country: Canada
facility: LMC Diabetes & Endocrinology Ltd. - Thornhill
state: Ontario
city: Etobicoke
country: Canada
facility: LMC Diabetes & Endocrinology Ltd. - Etobicoke
state: Ontario
city: London
country: Canada
facility: Centre for Studies in Family Medicine, Western Centre for Public Health and Family Medicine, Western University
state: Ontario
city: Toronto
country: Canada
facility: LMC Diabetes & Endocrinology Ltd. - Toronto
state: Ontario
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Québec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie De Quebec
state: Quebec
city: Jaroměř
country: Czechia
facility: Edumed s.r.o.
city: Pardubice
country: Czechia
facility: Nemocnice Pardubickeho kraje, a.s., Nemocnice Pardubice
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Bondy
country: France
facility: Hôpital Jean-Verdier - AP-HP; Service Endocrinologie Diabétologie Nutrition
city: Créteil
country: France
facility: CHU Henri Mondor
city: Nantes
country: France
facility: CHU de Nantes, Clinique d'Endocrinologie
city: Valenciennes
country: France
facility: Centre Hospitalier de Valenciennes
city: Frankfurt (Oder)
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
state: Brandenburg
city: Bad Oeynhausen
country: Germany
facility: Herz-und Diabeteszentrum NRW Universitaetsklinik der Ruhr-Universitaet Bochum
state: North Rhine Westphalia
city: Dresden
country: Germany
facility: Cardiologicum Pirna und Dresden
state: Saxony
city: Berlin
country: Germany
facility: Klinische Forschung Berlin GbR
city: Elsterwerda
country: Germany
facility: ZKS - Zentrum Klinische Studien Sudbrandenburg GmbH
city: Sha Tin
country: Hong Kong
facility: Erik Yee Mun George Fung
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital; Chinese University of Hong Kong; Dept of Medicine and Therapeutics
city: Wrocław
country: Poland
facility: Centrum Chorob Serca w USK
state: Borowska
city: Białystok
country: Poland
facility: NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny
city: Kraków
country: Poland
facility: Topolowa MEDICENTER Mrózek & wspólnicy sp.j.
city: Kraków
country: Poland
facility: Centrum Twojego Zdrowia
city: Poznań
country: Poland
facility: Praktyka Lekarska Ewa Krzyzagorska
city: Radom
country: Poland
facility: Prywatny Gabinet Lekarski Centrum Medyczne Diabetika
city: Rzeszów
country: Poland
facility: Centrum Medyczne Medyk Stanislaw Mazur Sp. z o.o. SK
city: Wrocław
country: Poland
facility: 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu
city: Łódź
country: Poland
facility: ETG Lodz
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
state: Murcia
city: A Coruña
country: Spain
facility: Hospital Abente y Lago (Complejo Universitario de la Coruña)
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau Barcelona
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Dundee
country: United Kingdom
facility: Ninewells Hospital & Medical School
city: Glasgow
country: United Kingdom
facility: CPS Research
city: Leicester
country: United Kingdom
facility: Glenfield hospital
city: London
country: United Kingdom
facility: Barts and The London School of Medicine & Dentistry
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
Study officials:
affiliation: Harvard Medical School (HMS and HSDM)
name: James L Januzzi, MD
role: STUDY_CHAIR
References: