Clinical trial NCT04125732: Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (The EXACT Trial)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Coronary Artery Disease
Ischemia
Angina Refractory
Cardiovascular Diseases
Heart Diseases
Keywords: Refractory angina
Coronary Artery Disease
Gene Therapy
Lead sponsor: XyloCor Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-10-14
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary Endpoint (adverse events)
timeFrame: 6 months
Secondary outcomes:
measure: Secondary Endpoint (Exercise tolerance test)
timeFrame: 6 months
measure: Secondary Endpoint (Seattle Angina Questionnaire)
timeFrame: 6 months
measure: Secondary Endpoint (Canadian Cardiovascular Society angina class)
timeFrame: 6 months
measure: Secondary Endpoint (Angina episodes)
timeFrame: 6 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Daytona Beach
country: United States
facility: Cardiology Research Associates
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: James A. Haley VA Medical Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital / The Lindner Research Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References:
citation: Stewart DJ, Hilton JD, Arnold JM, Gregoire J, Rivard A, Archer SL, Charbonneau F, Cohen E, Curtis M, Buller CE, Mendelsohn FO, Dib N, Page P, Ducas J, Plante S, Sullivan J, Macko J, Rasmussen C, Kessler PD, Rasmussen HS. Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus maximum medical treatment. Gene Ther. 2006 Nov;13(21):1503-11. doi: 10.1038/sj.gt.3302802. Epub 2006 Jun 22.
citation: 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. doi: 10.1016/j.ahj.2021.06.013. Epub 2021 Jul 2.