Enavogliflozin for the Management of Patients With Amyloid CardiomyopaThy

NCT07240844 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: EMPACTKC25MIDV0449
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Amyloid Cardiomyopathy

Keywords

Amyloid Cardiomyopathy; Enavogliflozin; Sodium-Glucose Cotransporter 2 Inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change in 6-Minute Walk Distance

  Baseline and Week 12

• Change in log-transformed NT-proBNP levels

  Baseline and Week 12

• Change in Body Weight

  Baseline and Week 12

• Change in Body Fat Percentage

  Baseline and Week 12

• Change in Extracellular Water Ratio

  Baseline and Week 12

Other Outcomes (1)

• Change in maximal oxygen consumption (VO₂ max)

  Baseline and Week 12

Study Arms (2)

Enavogliflozin

EXPERIMENTAL

Administer Enavogliflozin 0.3 mg

Drug: Enavogliflozin 0.3mg

Placebo

PLACEBO COMPARATOR

Administer placebo

Drug: Placebo

Interventions

Enavogliflozin 0.3mg DRUG

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.

Enavogliflozin

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Pregnant or breastfeeding women
• Active infection
• Major cardiovascular events (e.g., myocardial infarction, stroke) within the past 6 months
• Scheduled for coronary revascularization, CRT-D implantation, atrial flutter/fibrillation ablation, or valve surgery
• History of heart transplantation
• Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73 m² (calculated by CKD-EPI formula)
• 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)
• Heart failure primarily caused by severe left sided valvular disease or ischemic heart disease (except if valvular disease is corrected)
• Type 1 diabetes mellitus or insulin-dependent diabetes
• History of ketoacidosis, complicated urinary or genital infections, or kidney stones
• Systolic blood pressure \< 80 mmHg or symptomatic hypotension
• Major surgery within 90 days prior to enrollment
• Known hypersensitivity or allergic reaction to the study drug or its components
• Moderate to severe liver impairment
• Chronic alcohol or substance abuse

Sponsors & Collaborators

• Seoul St. Mary's Hospital: lead
• Samsung Medical Center: collaborator

Study Sites (2)

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul St. Mary's Hospital, The Catholic University of Korea

Seoul, 06591, South Korea

Location

Related Publications (2)

• 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.

  PMID: 38866445 RESULT

• 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.

  PMID: 37621153 RESULT

MeSH Terms

Conditions

Amyloid Neuropathies, Familial

Interventions

Enavogliflozin

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies

Study Officials

• Jong-Chan Youn, MD, PhD

  Seoul St. Mary's Hospital, The Catholic University of Korea

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jong-Chan Youn, MD, PhD

CONTACT

82-2-3147-9853; jong.chan.youn@gmail.com

Maljoung Ahn, RN

CONTACT

82-2-3147-9853; cmccasc@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prospective, multi-center, double-blind, randomized controlled, crossover, superiority trial

Study Record Dates

• First Submitted: September 28, 2025
• First Posted: November 21, 2025
• Study Start: November 24, 2025
• Primary Completion (Estimated): April 29, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: November 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked.
• Access Criteria: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked.

Locations

KR (2)