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

Phase 1

Completed

• Conditions: Ischemia; Cardiovascular Diseases; Heart Diseases; Coronary Artery Disease; Angina Refractory
• Interventions: Biological: AdVEGFXC1

• Registration Number: NCT04125732
• Lead Sponsor: XyloCor Therapeutics, Inc.

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.

Study Timeline

• Study First Submitted: 2019-10-04
• Study First Submitted QC: 2019-10-11
• Study First Posted: 2019-10-14
• Study Start: 2020-01-24
• Primary Completion: 2023-01-31
• Study Completion: 2023-05-30
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-29
• Last Update Posted: 2024-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
AdVEGFXC1 at 1x10^10 vp	AdVEGFXC1	-
AdVEGFXC1 at 4x10^10 vp	AdVEGFXC1	-
AdVEGFXC1 at 1x10^9 vp	AdVEGFXC1	-
AdVEGFXC1 at 1x10^11 vp	AdVEGFXC1	-

Primary Outcome Measures

Name	Time	Method
Primary Endpoint (adverse events)	6 months	Safety, as assessed by adverse events and serious adverse events

Secondary Outcome Measures

Name	Time	Method
Secondary Endpoint (Canadian Cardiovascular Society angina class)	6 months	Canadian Cardiovascular Society angina class
Secondary Endpoint (Angina episodes)	6 months	Angina episodes
Secondary Endpoint (Seattle Angina Questionnaire)	6 months	Seattle Angina Questionnaire
Secondary Endpoint (Exercise tolerance test)	6 months	Exercise tolerance test

Trial Locations

Locations (16)

MedStar Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

Cardiology Research Associates; 🇺🇸 Daytona Beach, Florida, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Lehigh Valley Health Network; 🇺🇸 Allentown, Pennsylvania, United States

The Ohio State University; 🇺🇸 Columbus, Ohio, United States

Minneapolis Heart Institute Foundation; 🇺🇸 Minneapolis, Minnesota, United States

The Christ Hospital / The Lindner Research Center; 🇺🇸 Cincinnati, Ohio, United States

James A. Haley VA Medical Center; 🇺🇸 Tampa, Florida, United States

Houston Methodist; 🇺🇸 Houston, Texas, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Texas Heart Institute; 🇺🇸 Houston, Texas, United States

Stanford University; 🇺🇸 Stanford, California, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

University of Washington; 🇺🇸 Seattle, Washington, United States