Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Preserved Ejection Fraction (MUSIC-HFpEF)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure, Diastolic; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Biological: AAV1/SERCA2a

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sardocor; Phone Number: 858-752-2941; Email: info@sardocorcorp.com

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University
      • Contact: Kay Doukellis; Email: katheryn.doukellis@duke.edu
  • Texas
    • Dallas, Texas, United States, 75390
      • Not yet recruiting
      • University of Texas Southwestern Medical Center
      • Contact: Therese Vallina; Email: Therese.Vallina@UTSouthwestern.edu

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SRD-001 Gene Therapy; AAV1/SERCA2a 3E13 vg	Biological: AAV1/SERCA2a; 3E13 viral genomes fixed dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pulmonary capillary wedge pressure (PCWP)	PCWP assessed by right heart catheterization; change in mmHg from baseline	Week 24 and Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PCWP at 20W exercise	PCWP assessed by right heart catheterization; change in mmHg from baseline	Week 24 and Week 52
Change in oxygen uptake (VO2) during exercise	VO2 assessed by bicycle exercise; change in mL/min from baseline	Week 24 and Week 52
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
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
Change in left atrial end systolic volume	Assessed by transesophageal echocardiography (ultrasound); change in mL/m2 from baseline	Week 24 and Week 52
Change in left atrial reservoir strain	Assessed by transesophageal echocardiography (ultrasound); change in %from baseline	Week 24 and Week 52
Change in left atrial contractile strain	Assessed by transesophageal echocardiography (ultrasound); change in % from baseline	Week 24 and Week 52
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
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
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
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

Collaborators and Investigators

• Sponsor: Sardocor Corp.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2023
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: July 30, 2023
• First Submitted That Met QC Criteria: September 23, 2023
• First Posted (Actual): September 29, 2023

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 23, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Diastolic
• Other Study ID Numbers: SRD-001-1003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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