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

Study Overview
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Brief Summary
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The primary purpose of this trial is to determine the safety of XC001 (AdVEGFXC1) in patients who suffer from angina caused by coronary artery disease and have no other treatment options. Subjects in this study will receive one of four intramyocardial doses of XC001 that expresses human vascular endothelial growth factor (VEGF) which induces therapeutic angiogenesis (revascularization).

Detailed Description
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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.

Official Title
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A Phase 1/2 Trial of Direct Administration of AdVEGF-All6A+, a Replication Deficient Adenovirus Vector Expressing a cDNA/Genomic Hybrid of Human VEGF, to the Ischemic Myocardium of Subjects With Angina Pectoris

Conditions
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Coronary Artery Disease, Ischemia, Angina Refractory, Cardiovascular Diseases, Heart Diseases

Intervention / Treatment
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* Biological: AdVEGFXC1


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AdVEGFXC1 at 1x10^9 vp<br> | Biological: AdVEGFXC1<br>* AdVEGFXC1 at one of 4 doses<br>* Other names: XC001;|
| Experimental: AdVEGFXC1 at 1x10^10 vp<br> | Biological: AdVEGFXC1<br>* AdVEGFXC1 at one of 4 doses<br>* Other names: XC001;|
| Experimental: AdVEGFXC1 at 4x10^10 vp<br> | Biological: AdVEGFXC1<br>* AdVEGFXC1 at one of 4 doses<br>* Other names: XC001;|
| Experimental: AdVEGFXC1 at 1x10^11 vp<br> | Biological: AdVEGFXC1<br>* AdVEGFXC1 at one of 4 doses<br>* Other names: XC001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoint (adverse events) | Safety, as assessed by adverse events and serious adverse events | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Endpoint (Exercise tolerance test) | Exercise tolerance test | 6 months | 
| Secondary Endpoint (Seattle Angina Questionnaire) | Seattle Angina Questionnaire | 6 months | 
| Secondary Endpoint (Canadian Cardiovascular Society angina class) | Canadian Cardiovascular Society angina class | 6 months | 
| Secondary Endpoint (Angina episodes) | Angina episodes | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene Therapy, Refractory angina, Coronary Artery Disease