Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (The EXACT Trial)

This is a Phase 1/2, first-in-human, multicenter, open-label, single arm dose escalation trial of XC001. Approximately 12 subjects (N=3 per cohort) who have refractory angina will be enrolled into 4 ascending dose groups, followed by an expansion of the highest tolerated dose with 32 additional subjects. XC001 will be administered by a transthoracic epicardial procedure. Safety will be the focus for the initial 6 months after XC001 administration followed by one safety focused telephone evaluation at Month 12.

Inclusion criteria

• Males and females, age 18 to 80 years
• Diagnosis of chronic angina due to obstructive coronary artery disease that is refractory to drug therapy and unsuitable for revascularization via coronary artery bypass graft or percutaneous coronary intervention
• Angina class II-IV based on Canadian Cardiovascular Society Classification of Angina Pectoris
• Adequate hematologic (hemoglobin ≥ 10 g/dL, absolute neutrophil count > 1.2 × 10^3 per μL and platelet count ≥ 75,000 per μL), hepatic (alanine aminotransferase and aspartate aminotransferase ≤ 3 x ULN; total bilirubin ≤ 2 x ULN), and renal function (glomerular filtration rate > 29 mL/minute/1.73 m2)
• Adequate birth control if of child-bearing potential
• Must be willing and able to provide informed consent

Exclusion criteria

• ST elevation myocardial infarction (STEMI) or non-ST elevation myocardial infarction (NSTEMI) not requiring revascularization, transmural myocardial infarction or cerebral vascular accident within the past 30 days
• New York Heart Association Function Class III or IV or left ventricular ejection fraction < 25% within the 6 weeks prior to the screening visit
• HbA1c ≥ 8.5%, SBP <90 or >180 mmHg, DBP >100 mmHg
• Other concurrent medical conditions that could jeopardize the safety of the subject or objectives of the study