Clinical trial NCT06061549: Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Preserved Ejection Fraction
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Heart Failure, Diastolic
Heart Failure With Preserved Ejection Fraction
Lead sponsor: Sardocor Corp.
Sponsor class: INDUSTRY
First posted: 2023-09-29
Enrollment: 10
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in pulmonary capillary wedge pressure (PCWP)
timeFrame: Week 24 and Week 52
Secondary outcomes:
measure: Change in PCWP at 20W exercise
timeFrame: Week 24 and Week 52
measure: Change in oxygen uptake (VO2) during exercise
timeFrame: Week 24 and Week 52
measure: Change in left ventricular (LV) relaxation
timeFrame: Week 24 and Week 52
measure: Change in NT-proBNP
timeFrame: Week 24 and Week 52
measure: Change in left atrial end systolic volume
timeFrame: Week 24 and Week 52
measure: Change in left atrial reservoir strain
timeFrame: Week 24 and Week 52
measure: Change in left atrial contractile strain
timeFrame: Week 24 and Week 52
measure: Change in 6 Minute Walk Distance
timeFrame: Week 24 and Week 52
measure: Change in 6 Minute Walk Test Borg scale
timeFrame: Week 24 and Week 52
measure: Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
timeFrame: Week 24 and Week 52
measure: Change in New York Heart Association class
timeFrame: Week 24 and Week 52
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
References: