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

Phase 1

Recruiting

• Conditions: Heart Failure, Diastolic; Heart Failure With Preserved Ejection Fraction
• Interventions: Biological: AAV1/SERCA2a

• Registration Number: NCT06061549
• Lead Sponsor: Sardocor Corp.

Brief 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.

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 Timeline

• Study First Submitted: 2023-07-30
• Study Start: 2023-08-24
• Status Verified: 2023-09
• Study First Submitted QC: 2023-09-23
• Last Update Submitted: 2023-09-23
• Study First Posted: 2023-09-29
• Last Update Posted: 2023-09-29
• Primary Completion: 2025-08
• Study Completion: 2029-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SRD-001 Gene Therapy	AAV1/SERCA2a	AAV1/SERCA2a 3E13 vg

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in oxygen uptake (VO2) during exercise	Week 24 and Week 52	VO2 assessed by bicycle exercise; change in mL/min from baseline
Change in left atrial contractile strain	Week 24 and Week 52	Assessed by transesophageal echocardiography (ultrasound); change in % from baseline
Change in NT-proBNP	Week 24 and Week 52	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
Change in 6 Minute Walk Test Borg scale	Week 24 and Week 52	Self-rated shortness of breath score with scale from 0 to 10, ranging from none to very, very severe
Change in New York Heart Association class	Week 24 and Week 52	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
Change in PCWP at 20W exercise	Week 24 and Week 52	PCWP assessed by right heart catheterization; change in mmHg from baseline
Change in left ventricular (LV) relaxation	Week 24 and Week 52	Assessed by transesophageal echocardiography (ultrasound) using 2 methods: LV global peak early diastolic strain rate (1/s) and LV tau
Change in left atrial end systolic volume	Week 24 and Week 52	Assessed by transesophageal echocardiography (ultrasound); change in mL/m2 from baseline
Change in left atrial reservoir strain	Week 24 and Week 52	Assessed by transesophageal echocardiography (ultrasound); change in %from baseline
Change in 6 Minute Walk Distance	Week 24 and Week 52	Distance walked in 6 minutes, measured in meters; the longer distance walked, the better medical condition
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score	Week 24 and Week 52	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

Trial Locations

Locations (2)

Duke University; 🇺🇸 Durham, North Carolina, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States