Investigational Trial to Evaluate XC001 Delivered Via an Cardiac Catheter in Subjects With Chronic Angina.

NCT07048808 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: XC001-1002
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two-part study, comprised of an initial open-label run-in phase (Part 1) in a subset of 3 subjects to provide first data regarding safety, and feasibility of the percutaneous endovascular catheter-facilitated intramyocardial delivery of XC001 in patients with RA due to obstructive CAD. Part 1 of the study is comprised of 3 subjects with RA (CCS class II-IV) who will receive 4×1011 viral particles (vp) XC001. An Independent Data Monitoring Committee (IDMC), the committee will review safety and feasibility data and approval to commence enrollment in Part 2 of the study. Part 2 is a randomized, double-blind, sham-procedure control study. Subjects with RA (CCS class II-IV) with no therapeutic options will be randomized 1:1 to either the treatment group with catheter delivery of 4×1011 vp XC001 (approximately N=53) or a sham procedure group (approximately N=53). It is estimated that approximately 106 subjects will be randomized to result in 100 evaluable subjects. All subjects enrolled in Part 1, as well as Part 2 will follow all screening and safety monitoring procedures for up to 12 months (Table 2), and will be included in the safety analysis of the study.

Conditions

Refractory Angina; Coronary Artery Disease

Keywords

Angina; EXACT 2; Refractory angina

Outcome Measures

Primary Outcomes (1)

• Composite endpoint

  The primary objective of this study is to evaluate the effect of XC001 on a composite endpoint of a) TED from a graded treadmill test (ETT), as assessed by a core lab, b) angina frequency from a diary (extracting the 2 weeks prior to the Week 12 and Week 26 visit) and c) ischemic burden, as quantified by stress imaging by PET (as assessed by a core lab) at 12 and 26 weeks following a one-time endocardial administration to CAD patients with RA compared to the sham procedure.

  6 months

Study Arms (2)

Treatment group

ACTIVE COMPARATOR

Those randomized to the treatment group will have XC001 administered by percutaneous catheter delivery using the Extroducer® Infusion Catheter System (delivery catheter).

Combination Product: XC001

Sham group

SHAM COMPARATOR

Subjects randomized to the sham catheterization procedure group will receive the same procedure as the treatment group (with introduction of an iliofemoral or radial sheath, positioning of the pigtail catheter in the left ventricle, generation of ventriculograms, and mimicking of the injection procedure by the interventional team following a Cath Lab script), except they will not have the delivery catheter inserted and will not receive any endocardial injections

Combination Product: Sham (No Treatment)

Interventions

XC001 COMBINATION_PRODUCT

XC001 administered by percutaneous catheter delivery using the Extroducer® Infusion Catheter System.

Treatment group

Sham (No Treatment) COMBINATION_PRODUCT

Subjects randomized to the sham catheterization procedure group will receive the same procedure as the treatment group (with introduction of an iliofemoral or radial sheath, positioning of the pigtail catheter in the left ventricle, generation of ventriculograms, and mimicking of the injection procedure by the interventional team following a Cath Lab script), except they will not have the delivery catheter inserted and will not receive any endocardial injections

Sham group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females, age 18 to 85 years, inclusive, at the time of signing the ICF.
• Diagnosis of chronic angina due to obstructive CAD that is refractory to drug therapy and unsuitable for revascularization via coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) (as defined by ESC Joint Study Group on the Treatment of Refractory Angina Refractory, Mannheimer et al, EHJ 2002 and the 2013 ESC guidelines on the management of stable coronary artery disease, Montalescot et al, EHJ 2013; and Jolicoeur et al 2008).
• Angina class II-IV as measured by CCS Functional Classification of Angina Pectoris.
• History of evidence of reversible left ventricular ischemia, as assessed by stress ECG (including screening), stress echocardiography, single- photon emission computed tomography (SPECT), CT angiography imaging with fractional flow reserve analysis, stress PET (including screening) or cardiac magnetic resonance (CMR) imaging that has not resolved with intervention or by an acute coronary event.
• Coronary angiography (and/or computed tomography (coronary) angiography (CTA)) within the past 18 months unless there is a clinical indication to warrant a more current procedure as determined by the investigator.
• Two baseline ECG stress tests (treadmill test, modified Bruce protocol) that adhere to the following (details outlined in the ETT manual):
• i. A modified Bruce protocol that includes two three-minute warm- up stages of 1.7 mph/ 0% grade and 1.7 mph/ 5% grade.
• ii. TED of 90 seconds to 9.5 minutes that is limited/stopped because of angina (or angina equivalent).
• iii. The maximally allowed variation between two subsequent treadmill tests should not exceed 25% and should not exceed 75 seconds. The ETT core laboratory must review and approve the ETTs for eligibility.
• iv. The tests must be performed at least 48 hours apart from each other. v. A third test is permitted if the second test does not meet the criteria.
• On a stable regimen of anti-anginal, anti-hypertensive, and lipid lowering medications deemed medically appropriate for RA at the discretion of the investigator. The chronic anti-anginal regimen must include at least two functional classes at the maximally tolerated dose for the preceding 30 days prior to the screening visit (Jolicoeur 2008). Functional classes include beta-blockers, calcium channel blockers, (long-acting) nitrates, and metabolic modulators (i.e., ranolazine, trimetazidine, ivabradine, nicorandil). Use of fewer than two functional classes may be allowed if there is evidence of intolerance to those classes of anti-anginal medications.
• Formally approved by the ERC to undergo the study procedure by a review of past medical history and screening assessments, with emphasis on reversible left ventricular ischemia (further details provided in the ERC Charter).
• All subjects capable of procreation with their partners must agree to use a highly effective and medically accepted method of contraception for 6 months following the study procedure (Day 1) to avoid pregnancy (as defined in Appendix A). This is not required of female subjects who are either:
• Postmenopausal (defined as no menses for 12 months without an alternative medical cause) prior to screening. In addition, at least 2 high follicle stimulating hormone (FSH) measurements in the postmenopausal range must be used to confirm a postmenopausal state in women with less than 12 months of amenorrhea and not using hormonal contraception or hormonal replacement therapy; OR
• Surgically sterile (i.e., hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) at least 1 month prior to Screening

You may not qualify if:

• Any of the following:
• ST-Elevation or non-ST elevation myocardial infarction (STEMI or NSTEMI) not requiring revascularization, transmural MI, or cerebral vascular accident within the past 60 days prior to the screening visit.
• Uncontrolled hypercholesterolemia defined as low-density lipoprotein (LDL) above 190 mg/dL.
• Uncontrolled hypertension (systolic blood pressure \[BP\] \>180 mmHg, diastolic BP \>100 mmHg) despite maximal medical treatment.
• Current untreated malignant ventricular arrhythmias (with episode of sustained or non-sustained ventricular tachycardia (VT) in last 30 days; suspected/probable/definite).
• Current untreated bradyarrhythmia (\<50 bpm) for which a new artificial pacemaker placement is anticipated during the study period. A current pacemaker is allowed.
• Congestive heart failure defined as New York Heart Association Function Class III or IV or left ventricular ejection fraction \< 25% within the 6 weeks prior to the screening visit (or as assessed by the screening contrast Echo).
• Anginal episodes that routinely require the administration of opiates.
• Moderate to severe aortic valve stenosis (defined as Doppler echocardiography determined peak pressure gradient that exceeds 40 mm Hg (or Vmax \>3.2 m/s) and/or subjects with a mechanical valve in the aorta valve position.
• Presence of a ventricular thrombus (as defined by contrast transthoracic echocardiography at screening). Subjects may be rescreened after 6 weeks of adequate treatment and absence of ventricular thrombus by echocardiography.
• Body mass index \> 45 kg/m2.
• Hemoglobin \< 10 g/dL, absolute neutrophil count \< 1.2 × 103 per µL, platelet count \< 75,000 per µL, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 3 x upper limit of normal (ULN), total bilirubin \> 2 x ULN unless the subject has a previously known history of Gilbert's syndrome and estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2
• Diabetic with current glycosylated hemoglobin (HbA1c) \> 9.5% or active proliferative diabetic retinopathy.
• Documented active proliferative retinopathy from any cause (ETDRS \[Early Treatment Diabetic Retinopathy Study\] score \>35).
• Uncontrolled coagulation disorder (that cannot be corrected by pharmacotherapy)

Sponsors & Collaborators

• XyloCor Therapeutics, Inc.: lead

Study Sites (1)

Christ Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

MeSH Terms

Conditions

Angina Pectoris; Coronary Artery Disease

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

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

Study Officials

• Tim Henry, MD

  Christ Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dawn VP Clinical Operation, MSc.

CONTACT

888-290-0081; dawn.byrnes@xylocor.com

Brenda Senior Director Clinical Operations

CONTACT

888-290-0081; brenda.garrison@xylocor.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blinded trial, there is a blinded team at the CRO
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, sham-procedure control study. Subjects with RA (CCS class II-IV) with no therapeutic options will be randomized 1:1 to either the treatment group with catheter delivery of 4×1011 vp XC001 (approximately N=53) or a sham procedure group (approximately N=53).

Study Record Dates

• First Submitted: June 24, 2025
• First Posted: July 2, 2025
• Study Start: June 24, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)