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

Coronary Artery Disease Clinical Trial

— EXACT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04125732
• Other study ID #: XC001-1001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 24, 2020
• Est. completion date: May 30, 2023

Study information

• Verified date: January 2024
• Source: XyloCor Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: May 30, 2023
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Angina Pectoris
• Angina Refractory
• Cardiovascular Diseases
• Coronary Artery Disease
• Coronary Disease
• Heart Diseases
• Ischemia
• Myocardial Ischemia

Intervention

Biological:
• AdVEGFXC1
AdVEGFXC1 at one of 4 doses

Locations

Country	Name	City	State
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Emory University	Atlanta	Georgia
United States	The Christ Hospital / The Lindner Research Center	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Cardiology Research Associates	Daytona Beach	Florida
United States	Duke University	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	Houston Methodist	Houston	Texas
United States	Texas Heart Institute	Houston	Texas
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	University of Washington	Seattle	Washington
United States	Stanford University	Stanford	California
United States	James A. Haley VA Medical Center	Tampa	Florida
United States	MedStar Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
XyloCor Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Endpoint (adverse events)	Safety, as assessed by adverse events and serious adverse events	6 months
Secondary	Secondary Endpoint (Exercise tolerance test)	Exercise tolerance test	6 months
Secondary	Secondary Endpoint (Seattle Angina Questionnaire)	Seattle Angina Questionnaire	6 months
Secondary	Secondary Endpoint (Canadian Cardiovascular Society angina class)	Canadian Cardiovascular Society angina class	6 months
Secondary	Secondary Endpoint (Angina episodes)	Angina episodes	6 months