Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Preserved Ejection Fraction

Heart Failure With Preserved Ejection Fraction Clinical Trial

— MUSIC-HFpEF  

Official title:

A Phase 1b, Pilot Trial Evaluating the Safety and Pharmacodynamic Effects of SRD-001 (AAV1-SERCA2a) in Subjects With Heart Failure With Preserved Ejection Fraction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06061549
• Other study ID #: SRD-001-1003
• Status: Recruiting
• Phase: Phase 1
• Start date: August 24, 2023
• Est. completion date: August 2029

Study information

• Verified date: September 2023
• Source: Sardocor Corp.
• Contact: Sardocor
• Phone: 858-752-2941
• Email: info[@]sardocorcorp.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to test an experimental gene therapy in participants with heart failure with preserved ejection fraction, also known as diastolic heart failure. The main questions it aims to answer are:

• safety and tolerability of the gene therapy; and

• whether the gene therapy helps the heart ventricles relax during filling. Participants will undergo a one-time infusion of the gene therapy in the cardiac catheterization laboratory and then be followed for safety and effects on left-sided filling pressures while exercising. The first year will have multiple in-person visits followed by 4 years of biannual phone calls.

Description:

Eligible participants will undergo a one-time antegrade epicardial coronary artery infusion of gene therapy delivered to the 3 major cardiac territories of the left ventricle of the heart (anterior, lateral, inferior/posterior) or bypass grafts unless contraindicated. Post-procedure, the subject will be monitored continuously for a minimum of 4 hours and then discharged to home that same day if medically appropriate. Participants will be followed for 52 weeks as part of the main trial. On Day 2 and Week 1, subjects will be contacted by phone for a general safety assessment, and if clinically indicated, an in-person evaluation and assessment will be performed as soon as possible. On Weeks 2, 4, 12, 24 and 52, subjects will undergo general safety assessments. Additionally, at Weeks 24 and 52, subjects will undergo outpatient core resting and exercise transthoracic echocardiography, right heart catheterization with hemodynamic monitoring and gas exchange measurements, 6-minute wall test, cardiac biomarker testing and completion the Kansas City Cardiomyopathy Questionnaire. Upon completion of the active observation period, participants will continue to be followed for 4 years with bi-annual, semi-structured telephone or in-person questionnaires that collect information on overall status and other comorbid conditions of interest in gene therapy trials.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: August 2029
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Willing and able to provide informed consent

• Negative for anti-AAV1 neutralizing antibodies

• NYHA class II or III

• Left ventricular ejection fraction = 50%

• Evidence of resting or exercise-induced left ventricle filling pressure

• On oral diuretic therapy

• Adequate birth control

Exclusion Criteria:

• NYHA class IV

• Heart failure requiring hospitalization in the past 3 months

• Manifested or provocable ischemic heart disease

• Atrial fibrillation

• History of congenital heart disease, restrictive or infiltrative cardiomyopathy, hypertrophic cardiomyopathy, acute myocarditis, pericardial disease, uncorrected thyroid disease or discrete left ventricular (LV) aneurysm

• History of amyloidosis

• Untreated left-sided valvular disease

• Severe COPD

• BMI > 50 kg/m^2

• Severe liver, kidney or hematologic dysfunction

• Cancer within the past 5 years

• Unstable concurrent conditions

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Heart Failure, Diastolic

Intervention

Biological:
• AAV1/SERCA2a
3E13 viral genomes fixed dose

Locations

Country	Name	City	State
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sardocor Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in pulmonary capillary wedge pressure (PCWP)	PCWP assessed by right heart catheterization; change in mmHg from baseline	Week 24 and Week 52
Secondary	Change in PCWP at 20W exercise	PCWP assessed by right heart catheterization; change in mmHg from baseline	Week 24 and Week 52
Secondary	Change in oxygen uptake (VO2) during exercise	VO2 assessed by bicycle exercise; change in mL/min from baseline	Week 24 and Week 52
Secondary	Change in left ventricular (LV) relaxation	Assessed by transesophageal echocardiography (ultrasound) using 2 methods: LV global peak early diastolic strain rate (1/s) and LV tau	Week 24 and Week 52
Secondary	Change in NT-proBNP	Laboratory measurement (picograms per mL) in blood; high levels indicate the heart is working too hard to pump blood; decrease over time would indicate an improvement in heart failure condition	Week 24 and Week 52
Secondary	Change in left atrial end systolic volume	Assessed by transesophageal echocardiography (ultrasound); change in mL/m2 from baseline	Week 24 and Week 52
Secondary	Change in left atrial reservoir strain	Assessed by transesophageal echocardiography (ultrasound); change in %from baseline	Week 24 and Week 52
Secondary	Change in left atrial contractile strain	Assessed by transesophageal echocardiography (ultrasound); change in % from baseline	Week 24 and Week 52
Secondary	Change in 6 Minute Walk Distance	Distance walked in 6 minutes, measured in meters; the longer distance walked, the better medical condition	Week 24 and Week 52
Secondary	Change in 6 Minute Walk Test Borg scale	Self-rated shortness of breath score with scale from 0 to 10, ranging from none to very, very severe	Week 24 and Week 52
Secondary	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score	Measures symptoms, physical and social limitations, and quality of life in patients with heart failure; 23-item self-administered questionnaire; score of 0 to 100; 0-24, very poor to poor; 25-49, poor to fair; 50 to 74, faire to good; and 75 to 100, good to excellent	Week 24 and Week 52
Secondary	Change in New York Heart Association class	Classification of heart failure based on severity of symptoms; 4 classes, I, II, III or IV where class I is having no symptoms doing ordinary physical activity; class II is having fatigue, shortness of breath, palpitations or angina with ordinary physical activity; class II is being comfortable only at rest; and class IV is having symptoms even at rest	Week 24 and Week 52