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

NCT ID: NCT04083339

Last Updated: 2022-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

675 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-20

Study Completion Date

2025-12-31

Brief Summary

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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

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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.

Conditions

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Diabetic Cardiomyopathies

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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).

Group Type EXPERIMENTAL

AT-001

Intervention Type DRUG

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

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).

Group Type EXPERIMENTAL

AT-001

Intervention Type DRUG

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 Comparator

Placebo capsules will be used as comparator

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Applied Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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James L Januzzi, MD

Role: STUDY_CHAIR

Harvard Medical School (HMS and HSDM)

Locations

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Westside Medical Associates of Los Angeles

Beverly Hills, California, United States

Site Status

University of California, San Diego (UCSD)

La Jolla, California, United States

Site Status

Clinical Trials Research

Lincoln, California, United States

Site Status

University of California - Irvine Medical Center

Orange, California, United States

Site Status

Metabolic Institute of America

Tarzana, California, United States

Site Status

Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center

Torrance, California, United States

Site Status

ALL Medical Research, LLC

Cooper City, Florida, United States

Site Status

New Generation of Medical Research

Hialeah, Florida, United States

Site Status

Broward Research Center

Pembroke Pines, Florida, United States

Site Status

Progressive Medical Research

Port Orange, Florida, United States

Site Status

UnityPoint Health - Methodist Hospital

Peoria, Illinois, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Universty of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

St. Louis Heart and Vascular Cardiology

St Louis, Missouri, United States

Site Status

Chear Center LLC

The Bronx, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Remington Davis, Inc.

Columbus, Ohio, United States

Site Status

South Oklahoma Heart Research

Oklahoma City, Oklahoma, United States

Site Status

Mountain View Clinical Research - Greer

Greer, South Carolina, United States

Site Status

Mountain View Clinical Research

Greer, South Carolina, United States

Site Status

Holston Medical Group

Kingsport, Tennessee, United States

Site Status

Dallas Diabetes Research Center

Dallas, Texas, United States

Site Status

Southwest Family Medicine Associates

Dallas, Texas, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

Juno Research, LLC - Northwest Site

Houston, Texas, United States

Site Status

Juno Research, LLC - Southwest Houston Site

Houston, Texas, United States

Site Status

FMC Science

Lampasas, Texas, United States

Site Status

Prince Charles Hospital

Chermside, Queensland, Australia

Site Status

CORE Research Group Pty. Ltd.

Milton, Queensland, Australia

Site Status

AusTrials

Taringa, Queensland, Australia

Site Status

University of Tasmania at Hobart

Hobart, Tasmania, Australia

Site Status

Barwon Health-University Hospital Geelong

Geelong, Victoria, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Baker Heart and Diabetes Institute

Melbourne, Victoria, Australia

Site Status

C-Endo - Endocrinology Centre

Calgary, Alberta, Canada

Site Status

BC Diabetes

Vancouver, British Columbia, Canada

Site Status

LMC Diabetes & Endocrinology Ltd. - Brampton

Brampton, Ontario, Canada

Site Status

LMC Diabetes & Endocrinology Ltd. - Thornhill

Concord, Ontario, Canada

Site Status

LMC Diabetes & Endocrinology Ltd. - Etobicoke

Etobicoke, Ontario, Canada

Site Status

Centre for Studies in Family Medicine, Western Centre for Public Health and Family Medicine, Western University

London, Ontario, Canada

Site Status

LMC Diabetes & Endocrinology Ltd. - Toronto

Toronto, Ontario, Canada

Site Status

Ecogene-21

Chicoutimi, Quebec, Canada

Site Status

Institut Universitaire de Cardiologie et de Pneumologie De Quebec

Québec, Quebec, Canada

Site Status

Edumed s.r.o.

Jaroměř, , Czechia

Site Status

Nemocnice Pardubickeho kraje, a.s., Nemocnice Pardubice

Pardubice, , Czechia

Site Status

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Site Status

Hôpital Jean-Verdier - AP-HP; Service Endocrinologie Diabétologie Nutrition

Bondy, , France

Site Status

CHU Henri Mondor

Créteil, , France

Site Status

CHU de Nantes, Clinique d'Endocrinologie

Nantes, , France

Site Status

Centre Hospitalier de Valenciennes

Valenciennes, , France

Site Status

Klinikum Frankfurt (Oder) GmbH

Frankfurt (Oder), Brandenburg, Germany

Site Status

Herz-und Diabeteszentrum NRW Universitaetsklinik der Ruhr-Universitaet Bochum

Bad Oeynhausen, North Rhine-Westphalia, Germany

Site Status

Cardiologicum Pirna und Dresden

Dresden, Saxony, Germany

Site Status

Klinische Forschung Berlin GbR

Berlin, , Germany

Site Status

ZKS - Zentrum Klinische Studien Sudbrandenburg GmbH

Elsterwerda, , Germany

Site Status

Erik Yee Mun George Fung

Shatin, , Hong Kong

Site Status

Prince of Wales Hospital; Chinese University of Hong Kong; Dept of Medicine and Therapeutics

Shatin, , Hong Kong

Site Status

Centrum Chorob Serca w USK

Wroclaw, Borowska, Poland

Site Status

NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny

Bialystok, , Poland

Site Status

Topolowa MEDICENTER Mrózek & wspólnicy sp.j.

Krakow, , Poland

Site Status

Centrum Twojego Zdrowia

Krakow, , Poland

Site Status

ETG Lodz

Lodz, , Poland

Site Status

Praktyka Lekarska Ewa Krzyzagorska

Poznan, , Poland

Site Status

Prywatny Gabinet Lekarski Centrum Medyczne Diabetika

Radom, , Poland

Site Status

Centrum Medyczne Medyk Stanislaw Mazur Sp. z o.o. SK

Rzeszów, , Poland

Site Status

4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu

Wroclaw, , Poland

Site Status

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Hospital Clinico Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain

Site Status

Hospital Abente y Lago (Complejo Universitario de la Coruña)

A Coruña, , Spain

Site Status

Hospital de la Santa Creu i Sant Pau Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario Reina Sofia

Córdoba, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Ninewells Hospital & Medical School

Dundee, , United Kingdom

Site Status

CPS Research

Glasgow, , United Kingdom

Site Status

Glenfield hospital

Leicester, , United Kingdom

Site Status

Barts and The London School of Medicine & Dentistry

London, , United Kingdom

Site Status

Wythenshawe Hospital

Manchester, , United Kingdom

Site Status

Countries

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

References

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Blumer V, Januzzi JL Jr, Liu Y, Butler J, Ezekowitz JA, Perfetti R, Rosenstock J, Del Prato S, Tang WHW, Urbinati A, Zannad F, Lewis GD, Solomon SD, Hedge S, Ibrahim NE, Lam CSP. Sex Differences in Diabetic Cardiomyopathy and Treatment Response to AT-001: Insights From the ARISE-HF Study. JACC Heart Fail. 2025 May 8:102433. doi: 10.1016/j.jchf.2025.02.015. Online ahead of print.

Reference Type DERIVED
PMID: 40338768 (View on PubMed)

Siddiqi TJ, Liu Y, Zannad F, Tang WHW, Solomon S, Rosenstock J, Perfetti R, Marwick TH, Lewis GD, Lam CSP, Ibrahim NE, Ezekowitz J, Del Prato S, Butler J, Januzzi JL. Health status in stage B heart failure from diabetic cardiomyopathy baseline results from ARISE-HF. J Diabetes Complications. 2025 Jul;39(7):109059. doi: 10.1016/j.jdiacomp.2025.109059. Epub 2025 Apr 25.

Reference Type DERIVED
PMID: 40315802 (View on PubMed)

Tang WHW, Liu Y, Butler J, Del Prato S, Ezekowitz JA, Ibrahim NE, Lam CSP, Marwick TH, Perfetti R, Rosenstock J, Solomon SD, Zannad F, Januzzi JL, Lewis GD. Impaired Exercise Capacity in High-Risk Diabetic Cardiomyopathy: The ARISE-HF Cardiopulmonary Exercise Testing Subanalysis. Circ Heart Fail. 2025 Mar;18(3):e012200. doi: 10.1161/CIRCHEARTFAILURE.124.012200. Epub 2025 Jan 30.

Reference Type DERIVED
PMID: 39882614 (View on PubMed)

Marwick TH, Lam C, Liu Y, Del Prato S, Rosenstock J, Butler J, Ezekowitz J, Ibrahim NE, Tang WHW, Zannad F, Perfetti R, Januzzi JL. Echocardiographic phenotypes of diabetic myocardial disorder: evolution over 15 months follow-up in the ARISE-HF trial. Cardiovasc Diabetol. 2025 Jan 13;24(1):16. doi: 10.1186/s12933-024-02554-y.

Reference Type DERIVED
PMID: 39806375 (View on PubMed)

Gouda P, Liu Y, Butler J, Del Prato S, Ibrahim NE, Lam CSP, Marwick T, Rosenstock J, Tang W, Zannad F, Januzzi J, Ezekowitz J. Relationship between NT-proBNP, echocardiographic abnormalities and functional status in patients with subclinical siabetic cardiomyopathy. Cardiovasc Diabetol. 2024 Aug 2;23(1):281. doi: 10.1186/s12933-024-02378-w.

Reference Type DERIVED
PMID: 39095808 (View on PubMed)

Lopez J, Liu Y, Butler J, Del Prato S, Ezekowitz JA, Lam CSP, Marwick TH, Rosenstock J, Tang WHW, Perfetti R, Urbinati A, Zannad F, Januzzi JL Jr, Ibrahim NE. Racial Differences in Diabetic Cardiomyopathy: The ARISE-HF Trial. J Am Coll Cardiol. 2024 Jul 16;84(3):233-243. doi: 10.1016/j.jacc.2024.04.053.

Reference Type DERIVED
PMID: 38986667 (View on PubMed)

Januzzi JL Jr, Butler J, Del Prato S, Ezekowitz JA, Ibrahim NE, Lam CSP, Lewis GD, Marwick TH, Perfetti R, Rosenstock J, Solomon SD, Tang WHW, Zannad F. Randomized Trial of a Selective Aldose Reductase Inhibitor in Patients With Diabetic Cardiomyopathy. J Am Coll Cardiol. 2024 Jul 9;84(2):137-148. doi: 10.1016/j.jacc.2024.03.380. Epub 2024 Apr 8.

Reference Type DERIVED
PMID: 38597864 (View on PubMed)

Januzzi JL, Del Prato S, Rosenstock J, Butler J, Ezekowitz J, Ibrahim NE, Lam CSP, Marwick T, Wilson Tang WH, Liu Y, Mohebi R, Urbinati A, Zannad F, Perfetti R. Characterizing diabetic cardiomyopathy: baseline results from the ARISE-HF trial. Cardiovasc Diabetol. 2024 Feb 1;23(1):49. doi: 10.1186/s12933-024-02135-z.

Reference Type DERIVED
PMID: 38302936 (View on PubMed)

Other Identifiers

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AT-001-2001

Identifier Type: -

Identifier Source: org_study_id

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