XC001 for Chronic Angina

(EXACT2 Trial)

Overseen By Dawn VP Clinical Operation, MSc.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: XyloCor Therapeutics, Inc.

Must be taking: Anti-anginal, anti-hypertensive

Disqualifiers: Recent MI, Uncontrolled hypertension, CHF, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

106 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called XC001 for individuals with chronic angina, a condition causing chest pain due to reduced blood flow to the heart. The trial evaluates the safety and potential effectiveness of delivering XC001 directly into the heart muscle using a special catheter. Suitable participants are those with persistent angina unresponsive to medications and not candidates for certain heart surgeries like bypass or stents. The study consists of two parts: the first involves a small group to test safety, and the second compares the treatment with a placebo group to assess effectiveness. Participants will be monitored for up to a year to ensure safety and gather results. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, you must be on a stable regimen of anti-anginal, anti-hypertensive, and lipid-lowering medications as deemed appropriate by the investigator.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that XC001, a new gene therapy for long-term chest pain (chronic angina), has promising safety results from earlier studies. This treatment uses a virus to deliver a gene that helps the heart grow new blood vessels, improving blood flow and reducing chest pain. In past studies, patients experienced no serious side effects from the treatment. Many patients could exercise more and had fewer chest pain episodes, suggesting that XC001 is generally well-tolerated. However, as it remains in the early testing stages, ongoing studies will continue to assess its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic angina?

Unlike the standard treatments for chronic angina, which often involve medications like nitrates, beta-blockers, or calcium channel blockers to manage symptoms, XC001 is unique because it is administered directly to the heart muscle through a specialized catheter system. This direct delivery method, using the Extroducer® Infusion Catheter System, targets the heart more precisely than traditional pills or injections. Researchers are excited about XC001 because it has the potential to improve heart function by promoting the growth of new blood vessels, which could offer a more lasting solution to angina symptoms compared to simply managing them with existing medications.

What evidence suggests that XC001 might be an effective treatment for chronic angina?

Research has shown that XC001, which participants in this trial may receive, could be a promising treatment for chronic angina, a type of chest pain. In earlier studies, patients who received XC001 exercised longer without discomfort, experienced better blood flow to the heart, and reported fewer angina symptoms. These benefits persisted for at least 12 months after treatment, indicating long-lasting effects. The treatment delivers genetic material to the heart to improve its function, offering hope for those with limited treatment options. ^{1 5 6 7 8}

Who Is on the Research Team?

Tim Henry, MD

Principal Investigator

Christ Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with chronic angina and coronary artery disease who have not responded to other treatments. Participants must be experiencing a certain level of chest pain (CCS class II-IV) and should not have any available therapeutic options left.

Inclusion Criteria

Coronary angiography (and/or CTA) within the past 18 months

Agree to use contraception if capable of procreation

Formally approved by the ERC to undergo the study procedure

Exclusion Criteria

Pregnancy or lactation, participation in other trials

Known allergy to nickel

I have a high BMI or abnormal blood, liver, or kidney tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Run-in

Initial open-label run-in phase to provide first data regarding safety and feasibility of XC001 delivery

4 weeks

1 visit (in-person)

Randomized Treatment

Randomized, double-blind, sham-procedure control study with catheter delivery of XC001 or sham procedure

26 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

Regular visits (in-person)

Extension

Optional extension phase for continued monitoring and safety analysis

26 weeks

What Are the Treatments Tested in This Trial?

Interventions

• XC001

Trial Overview The study tests XC001 delivered via cardiac catheter against a sham procedure in two parts: an initial phase for safety data from 3 subjects, followed by a randomized double-blind phase with about 106 subjects split evenly between treatment and sham groups.

How Is the Trial Designed?

Group I: Treatment group Active Control 1 Intervention

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

Group II: Sham group Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

XyloCor Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

40+

Citations

1. xylocor.com xylocor.com/pdfs/XyloCor-press-release-EXACT-12-month-results-2023-JUL18.pdf

XyloCor Therapeu.cs Reports Sustained Results in 12- ... -XC001 demonstrated durable improvements across mulfiple efficacy measures 12 months after treatment, underscoring its scienfifically-sound ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07048808

NCT07048808 | Investigational Trial to Evaluate XC001 ... Investigational Trial to Evaluate XC001 Delivered Via an Cardiac Catheter in Subjects With Chronic Angina. (EXACT2). ClinicalTrials.gov ID NCT07048808.

3. biospace.com biospace.com/xylocor-therapeutics-presents-phase-2-data-highlighting-safety-and-efficacy-of-xc001-at-the-european-society-of-cardiology-esc-congress-2023

XyloCor Therapeutics Presents Phase 2 Data Highlighting ... The six-month results showed that XC001 achieved a clinically meaningful biologic effect, warranting further study in larger randomized clinical ...

4. fh-partners.com fh-partners.com/news-entries/2023/7/18/xylocor-therapeutics-reports-sustained-results-in-12-month-extension-of-phase-2-exact-clinical-trial-of-xc001-novel-gene-therapy-for-refractory-angina

XyloCor Therapeutics Reports Sustained Results in 12 XC001 demonstrated durable improvements across multiple efficacy measures 12 months after treatment, underscoring its scientifically-sound ...

5. 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 ...

6. lumiraventures.com lumiraventures.com/news/xylocor-therapeutics-reports-positive-topline-safety-and-efficacy-results-from-phase-2-exact-clinical-trial-of-xc001-novel-gene-therapy-for-refractory-angina

XyloCor Therapeutics Reports Positive Topline Safety and ... No serious adverse events related to drug product were reported. Patients demonstrated improvements in exercise capacity and reductions in ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38696284/

Angiogenic Gene Therapy for Refractory Angina: Results of ... Conclusions: XC001 administered via transepicardial delivery is safe and generally well tolerated. Exploratory improvements in total exercise ...

8. xylocor.com xylocor.com/pdfs/XyloCor-PR-July-2021-V011D.pdf

XyloCor Therapeutics Commences Phase 2 Component of ... - Phase 2 clinical data readouts on safety and efficacy of XC001 anticipated in 2022. - ... chronic refractory angina, in 2020. About the ...