Enavogliflozin for the Management of Patients With Amyloid CardiomyopaThy (EMPACT)

Enavogliflozin for the Management of Patients With Amyloid CardiomyopaThy - A Randomized, Double-Blind, Placebo-Controlled, Crossover, Multicenter Trial

This study aims to evaluate the safety and effectiveness of Enavogliflozin 0.3 mg, an SGLT2 inhibitor, in patients with amyloid cardiomyopathy. Participants will take both the study drug and a placebo in two separate periods, with a wash-out period in between. The goal is to determine whether Enavogliflozin is safe and effective for treating amyloid cardiomyopathy.

Study Overview

• Status: Not yet recruiting
• Conditions: Amyloid Cardiomyopathy
• Intervention / Treatment: Drug: Enavogliflozin 0.3mg; Drug: Placebo

Detailed Description

Patients with a confirmed diagnosis of cardiac amyloidosis and symptomatic heart failure (NYHA class II-III) will be recruited.

Participants will be randomized to receive either the study drug or placebo and will undergo baseline and 12-week assessments, including the Kansas City Cardiomyopathy Questionnaire (KCCQ), 6-minute walk test, and cardiopulmonary exercise testing. Following a 4-week washout period, participants will cross over to the alternate treatment arm (study drug or placebo) and repeat the same assessments at baseline and 12 weeks.

The primary endpoint will be the change in KCCQ Clinical Summary Score (KCCQ-CSS).

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jong-Chan Youn, MD, PhD; Phone Number: 82-2-3147-9853; Email: jong.chan.youn@gmail.com
• Study Contact Backup: Name: Maljoung Ahn, RN; Phone Number: 82-2-3147-9853; Email: cmccasc@gmail.com

Study Locations

• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center
    • Sub-Investigator: David Hong, MD
    • Contact: Jin-Oh Choi, MD, PhD; Phone Number: 82-2-3410-3419; Email: choijean5@gmail.com
    • Sub-Investigator: Darae Kim, MD, PhD
  • Seoul, South Korea, 06591
    • Seoul St. Mary's Hospital, The Catholic University of Korea
    • Contact: Jong-Chan Youn, MD, PhD; Phone Number: 82-2-3147-9853; Email: jong.chan.youn@gmail.com
    • Contact: Maljoung Ahn, RN; Phone Number: 82-2-3147-9853; Email: cmccasc@gmail.com
    • Sub-Investigator: Mi-Hyang Jung, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults aged 19 years or older
2. Diagnosed with amyloid cardiomyopathy confirmed by cardiac biopsy or non-invasive imaging
3. Presence of heart failure symptoms corresponding to NYHA functional class II-III
4. Patients on stable oral diuretic use, without dose changes exceeding 50% of the previous dose, for at least 2 weeks prior to study enrollment
5. Ambulatory (able to walk)
6. Able to provide written informed consent for study participation

Exclusion Criteria:

1. Pregnant or breastfeeding women
2. Active infection
3. Major cardiovascular events (e.g., myocardial infarction, stroke) within the past 6 months
4. Scheduled for coronary revascularization, CRT-D implantation, atrial flutter/fibrillation ablation, or valve surgery
5. History of heart transplantation
6. Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² (calculated by CKD-EPI formula)
7. No history of cancer within the past 5 years at screening (except borderline cancers without recurrence for 2-3 years; multiple myeloma with cardiac involvement is classified as cardiac amyloidosis and is exempt)
8. Heart failure primarily caused by severe left sided valvular disease or ischemic heart disease (except if valvular disease is corrected)
9. Type 1 diabetes mellitus or insulin-dependent diabetes
10. History of ketoacidosis, complicated urinary or genital infections, or kidney stones
11. Systolic blood pressure < 80 mmHg or symptomatic hypotension
12. Major surgery within 90 days prior to enrollment
13. Known hypersensitivity or allergic reaction to the study drug or its components
14. Moderate to severe liver impairment
15. Chronic alcohol or substance abuse
16. Residing in long-term care facilities (e.g., nursing homes)
17. Unable to understand or comply with study drug, procedures, or follow-up, or who are deemed by the investigator to be unlikely to complete the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enavogliflozin; Administer Enavogliflozin 0.3 mg	Drug: Enavogliflozin 0.3mg; Participants will receive Enavogliflozin 0.3 mg orally once daily for 12 weeks. The drug is administered in tablet form and is taken during the first or second treatment period of a crossover design.
Placebo Comparator: Placebo; Administer placebo	Drug: Placebo; Participants will receive placebo orally once daily for 12 weeks. The drug is administered in tablet form and is taken during the first or second treatment period of a crossover design.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in KCCQ-CSS from baseline to Week 12	Change in the Clinical Summary Score of the Kansas City Cardiomyopathy Questionnaire (KCCQ-CSS) from baseline to 12 weeks after treatment initiation. The KCCQ-CSS is a patient-reported outcome measure that assesses symptom frequency and physical limitation in patients with heart failure. Scores range from 0 to 100, with higher scores indicating better symptom status and physical function (i.e., better health status). A higher change from baseline reflects an improvement in clinical status.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6-Minute Walk Distance	Change in distance walked in 6 minutes from baseline to Week 12. Higher distance indicates better exercise capacity.	Baseline and Week 12
Change in log-transformed NT-proBNP levels	Change in log-transformed NT-proBNP levels after 12 weeks of treatment compared to baseline	Baseline and Week 12
Change in Body Weight	Change in body weight in kilograms from baseline to Week 12	Baseline and Week 12
Change in Body Fat Percentage	Change in body fat percentage from baseline to Week 12	Baseline and Week 12
Change in Extracellular Water Ratio	Change in the ratio of extracellular water to total body water from baseline to Week 12	Baseline and Week 12
Incidence of Worsening Heart Failure Events or Death	Occurrence of worsening heart failure events (defined as emergency outpatient visit or unplanned hospitalization due to heart failure) or death	From baseline to Week 12 during each treatment period (excluding the 4-week washout period)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in maximal oxygen consumption (VO₂ max)	Change in VO₂ max measured by cardiopulmonary exercise testing (CPET) from baseline to Week 12. Higher values indicate better cardiorespiratory fitness.	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Seoul St. Mary's Hospital
• Collaborators: Samsung Medical Center
• Investigators: Principal Investigator: Jong-Chan Youn, MD, PhD, Seoul St. Mary's Hospital, The Catholic University of Korea

Publications and helpful links

General Publications

• Porcari A, Cappelli F, Nitsche C, Tomasoni D, Sinigiani G, Longhi S, Bordignon L, Masri A, Serenelli M, Urey M, Musumeci B, Cipriani A, Canepa M, Badr-Eslam R, Kronberger C, Chimenti C, Zampieri M, Allegro V, Razvi Y, Patel R, Ioannou A, Rauf MU, Petrie A, Whelan C, Emdin M, Metra M, Merlo M, Sinagra G, Hawkins PN, Solomon SD, Gillmore JD, Fontana M. SGLT2 Inhibitor Therapy in Patients With Transthyretin Amyloid Cardiomyopathy. J Am Coll Cardiol. 2024 Jun 18;83(24):2411-2422. doi: 10.1016/j.jacc.2024.03.429.
• Packer M, Butler J, Zeller C, Pocock SJ, Brueckmann M, Ferreira JP, Filippatos G, Usman MS, Zannad F, Anker SD. Blinded Withdrawal of Long-Term Randomized Treatment With Empagliflozin or Placebo in Patients With Heart Failure. Circulation. 2023 Sep 26;148(13):1011-1022. doi: 10.1161/CIRCULATIONAHA.123.065748. Epub 2023 Aug 24.

Study record dates

Study Major Dates

• Study Start (Estimated): November 24, 2025
• Primary Completion (Estimated): April 29, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: September 28, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Actual): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Amyloid Cardiomyopathy; Enavogliflozin; Sodium-Glucose Cotransporter 2 Inhibitor
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Proteostasis Deficiencies; Amyloid Neuropathies; Amyloidosis, Familial; Amyloidosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Amyloid Neuropathies, Familial; Enavogliflozin
• Other Study ID Numbers: EMPACT; KC25MIDV0449 (Other Identifier: Seoul St. Mary's Hospital, The Catholic University of Korea)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked.
• IPD Sharing Time Frame: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked.
• IPD Sharing Access Criteria: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No