A Study About the Natural History in Adults With BAG3 Dilated Cardiomyopathy (a Type of Heart Disease) (BAG3 DCM)

A PROSPECTIVE MULTINATIONAL STUDY OF THE NATURAL HISTORY OF PARTICIPANTS WITH BAG3 MUTATION ASSOCIATED DILATED CARDIOMYOPATHY

The purpose of this study is to learn about the natural progression of DCM (dilated cardiomyopathy) caused by BAG3 gene mutations. DCM is a condition as the heart muscle is weakened and the heart becomes enlarged. This makes it hard for the heart to pump enough blood for the body.

The study is seeking up to about 35 participants who have:

• BAG3 mutation (change in the gene) that causes or is likely to cause dilated cardiomyopathy
• NYHA (New York Heart Association) Class I-IV at screening (Stage B-D)
• Left Ventricular Ejection Fraction less than or equal to 50% (meaning reduced heart function)

All participants in this study will receive their usual treatment. The investigators will observe the natural progression of people who have BAG3 DCM. This will help the investigators better understand the disease and aid in future research.

Participants will take part in this study for one year. During this time, participants will visit the site at least 4 times (about every 3 months). Participants will undergo study procedures and give information about their health. These procedures will include a physical exam, cardiac magnetic resonance imaging, echocardiography, ECG monitoring, activity monitoring, cardiopulmonary exercise testing, and blood tests. Participants will answer questions about health and quality of life. The study team will also call participants about 1 time over the phone.

Study Overview

• Status: Recruiting
• Conditions: Cardiomyopathy, Dilated; Bcl-2 Anathogene-3 (BAG3) Dilated Cardiomyopathy (DCM)

• Study Type: Observational
• Enrollment (Estimated): 35

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Not yet recruiting
    • Maastricht University Medical Center
• Poland
  • Warszawa, Poland, 04-628
    • Recruiting
    • Narodowy Instytut Kardiologii Stefana kardynala Wyszynskiego - Panstwowy Instytut Badawczy
• Spain
  • A Coruna, Spain, 15006
    • Recruiting
    • CHUAC-Complejo Hospitalario Universitario A Coruña
  • Madrid, Spain, 28041
    • Not yet recruiting
    • Hospital Universitario 12 de octubre
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Recruiting
      • Hospital Universitario Puerta de Hierro Majadahonda
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Hospital Clinico Universitario Virgen de la Arrixaca
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Recruiting
    • Barts Health NHS Trust, St Bartholomew's Hospital
  • London
    • Harefield, London, United Kingdom, UB9 6JH
      • Recruiting
      • The Royal Brompton and Harefield Hospitals
• United States
  • California
    • Stanford, California, United States, 94304
      • Not yet recruiting
      • Stanford University Healthcare/Stanford Health Care
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • University of Colorado Hospital
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • University of Colorado Anschutz Medical Campus, Fitzsimons Building
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • University of Colorado Clinical and Translational Research Center
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • University of Colorado Denver, Anschutz Medical Campus
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham & Women's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic - Rochester
  • New York
    • Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
    • Bronx, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center(Hutchinson Metro Center)
    • Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center(Medical Arts Pavilion)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Division of Heart Failure and Transplantation(Hospital of the University of Pennsylvania)

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

primary care clinic and referrals from primary care clinic to investigational sites

Description

Key Inclusion Criteria:

• Documented BAG3 mutation that causes or is likely to cause dilated cardiomyopathy
• New York Heart Association (NYHA) Class I-IV at screening (Stage B-D)
• Left Ventricular Ejection Fraction ≤50% (i.e., Reduced Heart Function)

Key Exclusion Criteria:

• Acute decompensated heart failure within 1 month prior to enrollment.(such as hospitalization)
• Any of the following within 3 months prior to screening: myocardial infarction (MI), cardiac surgical procedures (other than for pacemaker/ICD/CRT-defibrillator [CRT-D] implantation), acute coronary syndrome, or hospitalization for cardiac arrhythmia.
• History of heart transplantation
• eGFR <30 mL/min/1.73 m2 (significantly impaired kidney function)
• Noncardiac condition that limits lifespan to <1 year.
• Presence of other form(s) of cardiomyopathy contributing to heart failure
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement).
• No more than 3 first-degree members of the same family who are already participating in the study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
BAG3 DCM; A single arm observational trial where all participants will undergo the same schedule of assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine baseline of cardiac structure and function in BAG3 associated DCM.	Baseline measures of left ventricular volumes at end systole and diastole using imaging at baseline.	Baseline
Determine changes over time in cardiac structure and function in BAG3 associated DCM.	Changes over time of left ventricular volumes at end systole and diastole using imaging over the course of one year follow up time.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in high sensitivity troponin I (hsTNI) levels	HsTNI will be collected at baseline through 1 year to observe the natural history (baseline and variance) of the biomarker and the correlation of hsTNI to severity of clinical disease progression.	Baseline to 1 year
Changes in high sensitivity troponin T (hsTNT) levels	HsTNT will be collected at baseline through 1 year to observe the natural history (baseline and variance) of the biomarker and the correlation of hsTNT to severity of clinical disease progression.	Baseline to 1 year
Changes in N-terminal Prohormone of Pro-Brain-Type Natriuretic peptide (NT-proBNP) levels	NT-proBNP will be collected at baseline through 1 year to observe the natural history (baseline and variance) of the biomarker and the correlation of NT-proBNP to severity of clinical disease progression.	Baseline to 1 year

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2022
• Primary Completion (Estimated): August 9, 2025
• Study Completion (Estimated): August 9, 2025

Study Registration Dates

• First Submitted: June 14, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: dilated cardiomyopathy; cardiomyopathy; heart disease; DCM; BAG3; heritable heart disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Heart Diseases; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: C4981001; 2022-000398-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

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