Clinical development and proof of principle testing of new regenerative vascular endothelial growth factor-D therapy for refractory angina: rationale and design of the phase 2 ReGenHeart trial

• Published in: Open heart Vol. 11; no. 2; p. e002817
• Main Authors: Leikas, Aleksi J, Hartikainen, Juha E K, Kastrup, Jens, Mathur, Anthony, Gyöngyösi, Mariann, Fernández-Avilés, Francisco, Sanz-Ruiz, Ricardo, Wojakowski, Wojtek, Gwizdała, Adrian, Luite, Riho, Nikkinen, Marko, Qayyum, Abbas A, Haack-Sørensen, Mandana, Kelham, Matthew, Jones, Daniel A, Hamzaraj, Kevin, Spannbauer, Andreas, Fernández-Santos, Maria E, Jędrzejek, Marek, Skoczyńska, Agnieszka, Vartiainen, Niklas, Knuuti, Juhani, Saraste, Antti, Ylä-Herttuala, Seppo
• Format: Journal Article
• Language: English
• Published: England British Cardiovascular Society 17.10.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Adenoviridae - genetics; Angina Pectoris; Angina Pectoris - diagnosis; Angina Pectoris - physiopathology; Angina Pectoris - therapy; Angiogenesis; Atherosclerosis; Blood pressure; Cardiovascular disease; Clinical Trials, Phase II as Topic; Coronary vessels; Double-Blind Method; Female; GENE THERAPY; Genetic Therapy - methods; Genetic Vectors; Heart attacks; Humans; Interventional cardiology; Ischemia; Leukocytes; Male; Medical imaging; Myocardial Perfusion Imaging - methods; Patients; Positron-Emission Tomography; Proof of Concept Study; Quality of Life; Randomized Controlled Trials as Topic; Tomography; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Vascular endothelial growth factor; Vascular Endothelial Growth Factor D; Vein & artery diseases; United States > US; Finland; New Brunswick New Jersey; GENE THERAPY; Positron-Emission Tomography; Angina Pectoris; Atherosclerosis
• ISSN: 2053-3624; 2398-595X; 2053-3624
• DOI: 10.1136/openhrt-2024-002817

BackgroundDespite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment options. Adenoviral vascular endothelial growth factor-DΔNΔC (AdVEGF-D)-encoding gene therapy (GT) holds promise for the treatment of refractory angina.MethodsReGenHeart is an investigator-initiated, multicentre, randomised, placebo-controlled and double-blinded phase 2 clinical trial that aims to study the safety and efficacy of intramyocardially administered angiogenic AdVEGF-D GT for refractory angina. Patients will be randomised in a 2:1 ratio and blocks of six to receive either AdVEGF-D or placebo. Primary endpoints are improvements in functional capacity assessed with the 6 min walking test and angina symptoms with Canadian Cardiovascular Society class after 6 month follow-up. Secondary endpoints are improvements in myocardial perfusion assessed with either positron emission tomography or single-photon emission CT after 6 month follow-up and functional capacity and angina symptoms after 12 months. In addition, changes in the quality of life, the use of angina medication and the incidence of major adverse cardiac and cerebrovascular events will be evaluated.ConclusionsThe phase 2 ReGenHeart trial will provide knowledge of the safety and efficacy of AdVEGF-D GT to ameliorate symptoms in refractory angina patients, extending and further testing positive results from the preceding phase 1/2a trial.