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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат AAV1/SERCA2a
  3E13 viral genomes fixed dose

Первичные конечные точки

• Change in pulmonary capillary wedge pressure (PCWP) [Срок оценки: Week 24 and Week 52]

Вторичные конечные точки (11)

• Change in PCWP at 20W exercise [Срок оценки: Week 24 and Week 52]
• Change in oxygen uptake (VO2) during exercise [Срок оценки: Week 24 and Week 52]
• Change in left ventricular (LV) relaxation [Срок оценки: Week 24 and Week 52]
• Change in NT-proBNP [Срок оценки: Week 24 and Week 52]
• Change in left atrial end systolic volume [Срок оценки: Week 24 and Week 52]
• Change in left atrial reservoir strain [Срок оценки: Week 24 and Week 52]
• Change in left atrial contractile strain [Срок оценки: Week 24 and Week 52]
• Change in 6 Minute Walk Distance [Срок оценки: Week 24 and Week 52]
• Change in 6 Minute Walk Test Borg scale [Срок оценки: Week 24 and Week 52]
• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score [Срок оценки: Week 24 and Week 52]
• Change in New York Heart Association class [Срок оценки: Week 24 and Week 52]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Duke University — Durham
• University of Texas Southwestern Medical Center — Dallas

Публикации

• Fudim M, Sarma S, MacNamara JP, Ascheim DD, Kittipibul V, Doukellis K, Dhimitri A, Fitzhugh R, Kamat N, Costa KD, Rudy J, Guerrero J, Chan C, Li RA, Bavry AA, Patel MR, Grodin JL, Levine BD, Hajjar RJ. Rationale and design of MUSIC-HFpEF: a phase 1b, pilot trial evaluating the safety and pharmacodynamic effects of AAV1.SERCA2A in heart failure with preserved ejection fraction. Heart Fail Rev. 2026 PMID 41546750

Идентификаторы

NCT: NCT06061549 · SRD-001-1003

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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