{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T06:01:39Z","timestamp":1771740099463,"version":"3.50.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Interventions"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>New therapies are needed for patients with refractory angina. Encoberminogene rezmadenovec (XC001), a novel adenoviral-5 vector coding for all 3 major isoforms of VEGF (vascular endothelial growth factor), demonstrated enhanced local angiogenesis in preclinical models; however, the maximal tolerated dose and safety of direct epicardial administration remain unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              In the phase 1 portion of this multicenter, open-label, single-arm, dose-escalation study, patients with refractory angina received increasing doses of encoberminogene rezmadenovec (1\u00d710\n              <jats:sup>9<\/jats:sup>\n              , 1\u00d710\n              <jats:sup>10<\/jats:sup>\n              , 4\u00d710\n              <jats:sup>10<\/jats:sup>\n              , and 1\u00d710\n              <jats:sup>11<\/jats:sup>\n              viral particles) to evaluate its safety, tolerability, and preliminary efficacy. Patients had class II to IV angina on maximally tolerated medical therapy, demonstrable ischemia on stress testing, and were angina-limited on exercise treadmill testing. Patients underwent minithoracotomy with epicardial delivery of 15 0.1-mL injections of encoberminogene rezmadenovec. The primary outcome was safety via adverse event monitoring over 6 months. Efficacy assessments included difference from baseline to months 3, 6 (primary), and 12 in total exercise duration, myocardial perfusion deficit using positron emission tomography, angina class, angina frequency, and quality of life.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              From June 2, 2020 to June 25, 2021, 12 patients were enrolled into 4 dosing cohorts with 1\u00d710\n              <jats:sup>11<\/jats:sup>\n              viral particle as the highest planned dose. Seventeen serious adverse events were reported in 7 patients; none were related to study drug. Six serious adverse events in 4 patients were related to the thoracotomy, 3 non\u2013serious adverse events were possibly related to study drug. The 2 lowest doses did not demonstrate improvements in total exercise duration, myocardial perfusion deficit, or angina frequency; however, there appeared to be improvements in all parameters with the 2 higher doses.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              Epicardial delivery of encoberminogene rezmadenovec via minithoracotomy is feasible, and up to 1\u00d710\n              <jats:sup>11<\/jats:sup>\n              viral particle appears well tolerated. A dose response was observed across 4 dosing cohorts in total exercise duration, myocardial perfusion deficit, and angina class. The highest dose (1\u00d710\n              <jats:sup>11<\/jats:sup>\n              viral particle) was carried forward into phase 2.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>REGISTRATION:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT04125732.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circinterventions.123.012997","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T09:00:37Z","timestamp":1690534837000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["EXACT Trial: Results of the Phase 1 Dose-Escalation Study"],"prefix":"10.1161","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct04125732","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0573-6565","authenticated-orcid":true,"given":"Thomas J.","family":"Povsic","sequence":"first","affiliation":[{"name":"Program for Advanced Coronary Disease, Duke University Medical Center and Duke Clinical Research Institute, Durham, NC (T.J.P., E.M.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1123-0533","authenticated-orcid":true,"given":"Timothy D.","family":"Henry","sequence":"additional","affiliation":[{"name":"The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital, Cincinnati, OH (T.D.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2108-0252","authenticated-orcid":true,"given":"Jay H.","family":"Traverse","sequence":"additional","affiliation":[{"name":"Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis (J.H.T., B.C.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3490-3286","authenticated-orcid":true,"given":"R. David","family":"Anderson","sequence":"additional","affiliation":[{"name":"University of Florida Heart and Vascular Center, Gainesville (R.D.A.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey A.","family":"Answini","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Christ Hospital, Cincinnati, OH (G.A.A.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin C.","family":"Sun","sequence":"additional","affiliation":[{"name":"Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis (J.H.T., B.C.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George J.","family":"Arnaoutakis","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida Heart and Vascular Center, Gainesville (G.J.A.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos D.","family":"Boudoulas","sequence":"additional","affiliation":[{"name":"Wexner Medical Center, Ohio State University, Columbus (K.D.B.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam R.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Duke University Medical Center, Durham, NC (A.R.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard C.","family":"Dittrich","sequence":"additional","affiliation":[{"name":"XyloCor Therapeutics, Malvern, PA (H.C.D., D.B., M.W.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Tarka","sequence":"additional","affiliation":[{"name":"Independent Consultant, Phoenixville, PA (E.A.T.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Latter","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, St Michael\u2019s Hospital, University of Toronto, Ontario, Canada (D.A.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Magnus","family":"Ohman","sequence":"additional","affiliation":[{"name":"Program for Advanced Coronary Disease, Duke University Medical Center and Duke Clinical Research Institute, Durham, NC (T.J.P., E.M.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark W.","family":"Peterson","sequence":"additional","affiliation":[{"name":"XyloCor Therapeutics, Malvern, PA (H.C.D., D.B., M.W.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn","family":"Byrnes","sequence":"additional","affiliation":[{"name":"XyloCor Therapeutics, Malvern, PA (H.C.D., D.B., M.W.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6011-681X","authenticated-orcid":true,"given":"Carl J.","family":"Pepine","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, University of Florida, Gainesville (C.J.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3119-025X","authenticated-orcid":true,"given":"Marcelo F.","family":"DiCarli","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.F.D.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald G.","family":"Crystal","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medicine, New York (R.G.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8519-0573","authenticated-orcid":true,"given":"Todd K.","family":"Rosengart","sequence":"additional","affiliation":[{"name":"Department of Surgery, Baylor College of Medicine, Houston, TX (T.K.R.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7189-5997","authenticated-orcid":true,"given":"Nahush A.","family":"Mokadam","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery, The Ohio State Wexner Medical Center, Columbus (N.A.M.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.10.044"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcin.2019.08.055"},{"key":"e_1_3_3_4_2","first-page":"353","article-title":"Health resource utilization and direct costs associated with angina for patients with coronary artery disease in a US managed care setting.","volume":"4","author":"Kempf J","year":"2011","unstructured":"Kempf, J, Buysman, E, Brixner, D. 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