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

NCT04125732 | Completed Phase 1 FDA Drug

• 1 other identifier: XC001-1001
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 16

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).

Conditions

Coronary Artery Disease; Ischemia; Angina Refractory; Cardiovascular Diseases; Heart Diseases

Keywords

Refractory angina; Coronary Artery Disease; Gene Therapy

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint (adverse events)

  Safety, as assessed by adverse events and serious adverse events

  6 months

Secondary Outcomes (4)

• Secondary Endpoint (Exercise tolerance test)

  6 months

• Secondary Endpoint (Seattle Angina Questionnaire)

  6 months

• Secondary Endpoint (Canadian Cardiovascular Society angina class)

  6 months

• Secondary Endpoint (Angina episodes)

  6 months

Study Arms (4)

AdVEGFXC1 at 1x10^9 vp

EXPERIMENTAL

Biological: AdVEGFXC1

AdVEGFXC1 at 1x10^10 vp

EXPERIMENTAL

Biological: AdVEGFXC1

AdVEGFXC1 at 4x10^10 vp

EXPERIMENTAL

Biological: AdVEGFXC1

AdVEGFXC1 at 1x10^11 vp

EXPERIMENTAL

Biological: AdVEGFXC1

Interventions

AdVEGFXC1 BIOLOGICAL

AdVEGFXC1 at one of 4 doses

Also known as: XC001

AdVEGFXC1 at 1x10^10 vp; AdVEGFXC1 at 1x10^11 vp; AdVEGFXC1 at 1x10^9 vp; AdVEGFXC1 at 4x10^10 vp

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• XyloCor Therapeutics, Inc.: lead

Study Sites (16)

Stanford University

Stanford, California, 94305, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Cardiology Research Associates

Daytona Beach, Florida, 32117, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

James A. Haley VA Medical Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

The Christ Hospital / The Lindner Research Center

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

Texas Heart Institute

Houston, Texas, 77030, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (4)

• 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.

  PMID: 16791287 BACKGROUND

• Nakamura K, Henry TD, Traverse JH, Latter DA, Mokadam NA, Answini GA, Williams AR, Sun BC, Burke CR, Bakaeen FG, DiCarli MF, Chaitman BR, Peterson MW, Byrnes DG, Ohman EM, Pepine CJ, Crystal RG, Rosengart TK, Kowalewski E, Koch GG, Dittrich HC, Povsic TJ; EXACT Trial Investigators. Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial. Circ Cardiovasc Interv. 2024 May;17(5):e014054. doi: 10.1161/CIRCINTERVENTIONS.124.014054. Epub 2024 May 2.

  PMID: 38696284 DERIVED

• Povsic TJ, Henry TD, Traverse JH, Anderson RD, Answini GA, Sun BC, Arnaoutakis GJ, Boudoulas KD, Williams AR, Dittrich HC, Tarka EA, Latter DA, Ohman EM, Peterson MW, Byrnes D, Pepine CJ, DiCarli MF, Crystal RG, Rosengart TK, Mokadam NA. EXACT Trial: Results of the Phase 1 Dose-Escalation Study. Circ Cardiovasc Interv. 2023 Aug;16(8):e012997. doi: 10.1161/CIRCINTERVENTIONS.123.012997. Epub 2023 Jul 28.

  PMID: 37503661 DERIVED

• 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.

  PMID: 34224684 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Ischemia; Cardiovascular Diseases; Heart Diseases; Angina Pectoris

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2019
• First Posted: October 14, 2019
• Study Start: January 24, 2020
• Primary Completion: January 31, 2023
• Study Completion: May 30, 2023
• Last Updated: January 30, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)