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

Primary Purpose

Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AAV1/SERCA2a
Sponsored by
Sardocor Corp.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure, Diastolic

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Duke UniversityRecruiting
  • University of Texas Southwestern Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SRD-001 Gene Therapy

Arm Description

AAV1/SERCA2a 3E13 vg

Outcomes

Primary Outcome Measures

Change in pulmonary capillary wedge pressure (PCWP)
PCWP assessed by right heart catheterization; change in mmHg from baseline

Secondary Outcome Measures

Change in PCWP at 20W exercise
PCWP assessed by right heart catheterization; change in mmHg from baseline
Change in oxygen uptake (VO2) during exercise
VO2 assessed by bicycle exercise; change in mL/min from baseline
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
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
Change in left atrial end systolic volume
Assessed by transesophageal echocardiography (ultrasound); change in mL/m2 from baseline
Change in left atrial reservoir strain
Assessed by transesophageal echocardiography (ultrasound); change in %from baseline
Change in left atrial contractile strain
Assessed by transesophageal echocardiography (ultrasound); change in % from baseline
Change in 6 Minute Walk Distance
Distance walked in 6 minutes, measured in meters; the longer distance walked, the better medical condition
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
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
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

Full Information

First Posted
July 30, 2023
Last Updated
September 23, 2023
Sponsor
Sardocor Corp.
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1. Study Identification

Unique Protocol Identification Number
NCT06061549
Brief Title
Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Preserved Ejection Fraction
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 24, 2023 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sardocor Corp.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SRD-001 Gene Therapy
Arm Type
Experimental
Arm Description
AAV1/SERCA2a 3E13 vg
Intervention Type
Biological
Intervention Name(s)
AAV1/SERCA2a
Intervention Description
3E13 viral genomes fixed dose
Primary Outcome Measure Information:
Title
Change in pulmonary capillary wedge pressure (PCWP)
Description
PCWP assessed by right heart catheterization; change in mmHg from baseline
Time Frame
Week 24 and Week 52
Secondary Outcome Measure Information:
Title
Change in PCWP at 20W exercise
Description
PCWP assessed by right heart catheterization; change in mmHg from baseline
Time Frame
Week 24 and Week 52
Title
Change in oxygen uptake (VO2) during exercise
Description
VO2 assessed by bicycle exercise; change in mL/min from baseline
Time Frame
Week 24 and Week 52
Title
Change in left ventricular (LV) relaxation
Description
Assessed by transesophageal echocardiography (ultrasound) using 2 methods: LV global peak early diastolic strain rate (1/s) and LV tau
Time Frame
Week 24 and Week 52
Title
Change in NT-proBNP
Description
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
Time Frame
Week 24 and Week 52
Title
Change in left atrial end systolic volume
Description
Assessed by transesophageal echocardiography (ultrasound); change in mL/m2 from baseline
Time Frame
Week 24 and Week 52
Title
Change in left atrial reservoir strain
Description
Assessed by transesophageal echocardiography (ultrasound); change in %from baseline
Time Frame
Week 24 and Week 52
Title
Change in left atrial contractile strain
Description
Assessed by transesophageal echocardiography (ultrasound); change in % from baseline
Time Frame
Week 24 and Week 52
Title
Change in 6 Minute Walk Distance
Description
Distance walked in 6 minutes, measured in meters; the longer distance walked, the better medical condition
Time Frame
Week 24 and Week 52
Title
Change in 6 Minute Walk Test Borg scale
Description
Self-rated shortness of breath score with scale from 0 to 10, ranging from none to very, very severe
Time Frame
Week 24 and Week 52
Title
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Description
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
Time Frame
Week 24 and Week 52
Title
Change in New York Heart Association class
Description
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
Time Frame
Week 24 and Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sardocor
Phone
858-752-2941
Email
info@sardocorcorp.com
Facility Information:
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kay Doukellis
Email
katheryn.doukellis@duke.edu
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Therese Vallina
Email
Therese.Vallina@UTSouthwestern.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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