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

Phase 3

Active, not recruiting

• Conditions: Diabetic Cardiomyopathies
• Interventions: Drug: AT-001; Drug: Placebo

• Registration Number: NCT04083339
• Lead Sponsor: Applied Therapeutics, Inc.

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 Timeline

• Study First Submitted: 2019-08-23
• Study First Submitted QC: 2019-09-05
• Study First Posted: 2019-09-10
• Study Start: 2019-09-20
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-07
• Last Update Posted: 2022-12-08
• Primary Completion: 2023-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 675

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AT-001 Low Dose	AT-001	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).
Placebo Comparator	Placebo	Placebo capsules will be used as comparator
AT-001 High dose	AT-001	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).

Primary Outcome Measures

Name	Time	Method
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).

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (79)

Westside Medical Associates of Los Angeles; 🇺🇸 Beverly Hills, California, United States

University of California, San Diego (UCSD); 🇺🇸 La Jolla, California, United States

Clinical Trials Research; 🇺🇸 Lincoln, California, United States

University of California - Irvine Medical Center; 🇺🇸 Orange, California, United States

Metabolic Institute of America; 🇺🇸 Tarzana, California, United States

Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center; 🇺🇸 Torrance, California, United States

ALL Medical Research, LLC; 🇺🇸 Cooper City, Florida, United States

New Generation of Medical Research; 🇺🇸 Hialeah, Florida, United States

Broward Research Center; 🇺🇸 Pembroke Pines, Florida, United States

Progressive Medical Research; 🇺🇸 Port Orange, Florida, United States

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