XC001 Gene Therapy for Coronary Artery Disease

(EXACT-CABG Trial)

Overseen By Dawn Byrnes, VP Clinical Operations, MSc.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: XyloCor Therapeutics, Inc.

Must not be taking: Corticosteroids, Cytostatics

Disqualifiers: STEMI, Hypertension, Heart failure, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 56

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test a new gene therapy treatment, XC001, for individuals with coronary artery disease (CAD) who require heart surgery but may not have all blocked arteries fully repaired. The study compares XC001 to a placebo to determine if it can improve blood flow to heart areas that regular surgery might not address. Candidates for the trial have significant CAD and are scheduled for heart bypass surgery (CABG), particularly if some heart areas won't benefit from surgery due to complex blockages. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in CAD treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor to get specific guidance based on your situation.

Is there any evidence suggesting that XC001 is likely to be safe for humans?

Previous studies have shown that XC001 is safe and generally well tolerated. Research involving 32 patients found that the gene therapy XC001 did not cause any serious side effects. During treatment, patients did not experience major negative reactions. XC001 is a gene therapy designed to improve blood flow to the heart by harnessing the body's natural processes. While results so far are promising, each person's experience may differ. Discuss any concerns about joining a trial with a healthcare professional. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about XC001 because it offers a novel approach to treating coronary artery disease. Unlike traditional treatments such as medications, lifestyle changes, or surgical interventions like angioplasty and coronary artery bypass grafting (CABG), XC001 is a gene therapy designed to enhance blood vessel growth. This new method targets the root cause of reduced blood flow by promoting angiogenesis, potentially improving heart function and reducing symptoms more effectively than conventional options. This innovative approach could lead to a more sustainable and long-term solution for patients, setting it apart from current treatment strategies.

What evidence suggests that XC001 might be an effective treatment for coronary artery disease?

Research has shown that XC001 gene therapy might alleviate symptoms of coronary artery disease (CAD). In one study, patients who received XC001 exercised longer, experienced better blood flow to their hearts, and had less chest pain. Another study found XC001 to be safe, with no serious side effects. This trial will include a treatment group receiving XC001 and a placebo group receiving A195/placebo. XC001 helps the heart grow new blood vessels, improving blood flow and reducing symptoms. Early results suggest that XC001 might alter the disease's course by reducing heart strain and discomfort. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with Coronary Artery Disease (CAD) who are scheduled for a bypass surgery (CABG) but have heart areas that won't get enough blood flow due to technical challenges. Participants should show significant ischemia in stress imaging and not be candidates for complete revascularization.

Inclusion Criteria

LVEF by standard quantitative imaging technique of 25% to 50%

All participants 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

Capable of providing informed consent and undergoing all the required tests and procedures in the protocol

Exclusion Criteria

My HbA1c level is above 9.5% or I have an advanced eye condition due to diabetes.

Body mass index (BMI) > 45 kg/m2

Hemoglobin < 10 g/dL, absolute neutrophil count < 1.2 × 103 per µL, platelet count < 75,000 per µL, alanine aminotransferase and aspartate aminotransferase > 3 × upper limit of normal (ULN), total bilirubin > 2 × ULN

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive XC001 or placebo injections during the final stages of the CABG procedure

26 weeks

Baseline CMR at day 4-6 post CABG, assessments on Day 14, and Weeks 4, 12, and 26

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

Assessments at 52 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

26 weeks

What Are the Treatments Tested in This Trial?

Interventions

• XC001

Trial Overview

The study tests XC001 gene therapy, delivered during CABG, against a placebo. It's designed to see if XC001 can promote new blood vessel growth in the heart. Patients will be randomly assigned to either the treatment or placebo group and monitored over 26 weeks, with an optional extension to 52 weeks.

How Is the Trial Designed?

Group I: Treatment group Experimental Treatment 1 Intervention

Administration of study drug (XC001) at the end of the CABG procedure.

Group II: Placebo group Placebo Group 1 Intervention

Administration of A195/placebo at the end of the CABG procedure.

Who Is Running the Clinical Trial?

XyloCor Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

40+

Citations

1.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.124.014054

Angiogenic Gene Therapy for Refractory Angina: Results of ...

In this open-label study, administration of XC001 resulted in improvements in exercise time, myocardial perfusion, and angina symptoms as ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04125732

NCT04125732 | Epicardial Delivery of XC001 Gene ...

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 ...

3.

scai.org

scai.org/media-center/news-and-articles/gene-therapy-treatment-increasing-bodys-signal-new-blood-vessel

Gene Therapy Treatment Increasing Body's Signal for New ...

Among the 32 patients with NORA, the gene therapy XC001 appeared safe with no serious adverse effects due to the drug. Surgical delivery was ...

4.

clinicaltrialsarena.com

clinicaltrialsarena.com/news/xylocor-trial-xc001/

XyloCor doses first subject in Phase IIb trial of XC001

The trial indicated the therapy's potential to modify the disease course, showing a decrease in cardiac ischemia and anginal symptoms, and an ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/34224684/

Epicardial delivery of XC001 gene therapy for refractory ...

The EXACT trial will determine whether direct intramyocardial administration of XC001 in patients with RA is safe and evaluate its effect on exercise tolerance.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11097950/

Angiogenic Gene Therapy for Refractory Angina

XC001 administered via transepicardial delivery is safe and generally well tolerated. Exploratory improvements in total exercise duration, ischemic burden, and ...

7.

xylocor.com

xylocor.com/news.html

News

XC001 is an investigational novel gene therapy designed to activate naturally occurring biological pathways to improve blood flow to areas of the heart not ...

8.

scge.mcw.edu

scge.mcw.edu/platform/data/clinicalTrials/report/NCT04125732

Gene Therapy Trial Report

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 ...