The purpose of this study is to evaluate the safety and efficacy of percutaneous endovascular catheter-facilitated intramyocardial delivery of XC001 in treating refractory angina compared to standard treatment.

XC001 is investigational, which means it is not approved by the U.S. Food and Drug Administration (FDA). XC001 is made of an adenovirus (one of the causes of the common cold). The adenovirus in XC001 has been genetically altered so it cannot reproduce or cause a cold, but instead is able deliver a potential therapeutic, vascular endothelial growth factor (VEGF), to the heart that promotes the growth of new blood vessels. This process is called gene transfer. VEGF is a factor that is involved in the growth of new blood vessels to stimulate better blood flow to the heart. The delivery of XC001 to the heart is performed in the cardiac catheterization lab (Cath Lab) by experienced cardiologists.

Participants will be randomized into one of two study groups to receive either the investigational procedure or the sham procedure.  Randomization is like flipping a coin and there is an equal chance of being assigned to either group. Participants will not know what group they are assigned to.

If randomized to the investigational procedure, the investigational drug XC001 will be administered with a specific medical device – an infusion catheter system called Extroducer®. The Extroducer® Infusion Catheter is an investigational medical device that is also not FDA-approved. XC001 is designed to promote new blood vessels in the heart, with these new blood vessels bypassing the blockage in the coronary arteries and improving blood flow in the heart.

If randomized to the sham procedure, participants will receive the same procedure as the treatment group (mimicking of the injection procedure by the interventional team following a Cath Lab script), except they will not have the delivery catheter inserted and will not receive any endocardial
injections.

Total study participation may last about 14 months. All study participants will be expected to complete one telephone assessment and a total of 8 study visits, which include exercise tests, scans, the procedure itself, and other post-procedure assessments.