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Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations.

Publication ,  Journal Article
Povsic, TJ; Henry, TD; Ohman, EM; Pepine, CJ; Crystal, RG; Rosengart, TK; Reinhardt, RR; Dittrich, HC; Traverse, JH; Answini, GA; Mokadam, NA
Published in: Am Heart J
November 2021

BACKGROUND: Patients with refractory angina (RA) have poor quality of life and new therapies are needed. XC001 is a novel adenoviral vector expressing multiple isoforms of vascular endothelial growth factor (VEGF) promoting an enhanced local angiogenic effect. METHODS: The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) trial is a 6-month (with 6-month extension) phase 1/2, first-in-human, multicenter, open-label, single-arm, dose-escalation study to evaluate the safety, tolerability, and preliminary efficacy of XC001 in patients with RA. The trial will enroll 33 patients in an initial (n = 12) ascending dose-escalation phase (1 × 109, 1 × 1010, 4 × 1010, and 1 × 1011 viral particles), followed by phase 2 (n = 21) assessing the highest tolerated dose. Patients must have stable Canadian Cardiovascular Society (CCS) class II-IV angina on maximally tolerated medical therapy without options for conventional revascularization, demonstrable ischemia on stress testing, and angina limiting exercise tolerance. XC001 will be delivered directly to ischemic myocardium via surgical transthoracic epicardial access. The primary outcome is safety via adverse event monitoring through 6 months. Efficacy assessments include difference from baseline to month 6 in time to 1 mm of ST segment depression, time to angina, and total exercise duration; myocardial blood flow at rest, and stress and coronary flow reserve by positron emission tomography; quality of life; CCS functional class; and angina frequency. CONCLUSIONS: The EXACT trial will determine whether direct intramyocardial administration of XC001 in patients with RA is safe and evaluate its effect on exercise tolerance, myocardial perfusion, angina and physical activity, informing future clinical investigation. CLINICAL TRIAL REGISTRATION: NCT04125732.

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Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

November 2021

Volume

241

Start / End Page

38 / 49

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factors
  • Treatment Outcome
  • Pericardium
  • Maximum Tolerated Dose
  • Male
  • Humans
  • Genetic Vectors
  • Genetic Therapy
  • Female
  • Exercise Tolerance
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Povsic, T. J., Henry, T. D., Ohman, E. M., Pepine, C. J., Crystal, R. G., Rosengart, T. K., … Mokadam, N. A. (2021). Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations. Am Heart J, 241, 38–49. https://doi.org/10.1016/j.ahj.2021.06.013
Povsic, Thomas J., Timothy D. Henry, E Magnus Ohman, Carl J. Pepine, Ronald G. Crystal, Todd K. Rosengart, Rickey R. Reinhardt, et al. “Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations.Am Heart J 241 (November 2021): 38–49. https://doi.org/10.1016/j.ahj.2021.06.013.
Povsic TJ, Henry TD, Ohman EM, Pepine CJ, Crystal RG, Rosengart TK, et al. Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations. Am Heart J. 2021 Nov;241:38–49.
Povsic, Thomas J., et al. “Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations.Am Heart J, vol. 241, Nov. 2021, pp. 38–49. Pubmed, doi:10.1016/j.ahj.2021.06.013.
Povsic TJ, Henry TD, Ohman EM, Pepine CJ, Crystal RG, Rosengart TK, Reinhardt RR, Dittrich HC, Traverse JH, Answini GA, Mokadam NA. Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations. Am Heart J. 2021 Nov;241:38–49.
Journal cover image

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

November 2021

Volume

241

Start / End Page

38 / 49

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factors
  • Treatment Outcome
  • Pericardium
  • Maximum Tolerated Dose
  • Male
  • Humans
  • Genetic Vectors
  • Genetic Therapy
  • Female
  • Exercise Tolerance