A Study of Encoberminogene Rezmadenovec Gene Therapy for Patients with Refractory Angina Due to Coronary Artery Disease

Baseline assessments and preparation

At the start of the trial, two baseline stress tests will be performed using a treadmill with a modified Bruce protocol. Each test will include two three-minute warm-up stages at 1.7 mph with 0% grade and then 5% grade. The test duration should be between 90 seconds and 9.5 minutes, and it will be stopped when chest pain or discomfort occurs.

These two tests must be performed at least 48 hours apart from each other. If the second test does not meet the criteria, a third test may be performed.

A stress imaging test using PET (positron emission tomography) will be performed to measure the amount of reduced blood flow to the heart muscle. This test uses 13N-ammonia and flurpiridaz F 18, both administered as solutions for injection into a vein.

An electronic diary will be provided to record daily chest pain episodes, their severity, and the use of nitroglycerin medication.

Treatment procedure on Day 1

The treatment will be administered on Day 1 of the trial. The procedure involves either receiving the investigational treatment or a sham procedure (a procedure that appears the same but does not include the active treatment).

If assigned to the treatment group, XC001 (encoberminogene rezmadenovec) will be administered as a one-time injection directly into the heart muscle using a specialized catheter called Extroducer. The medication is a solution for injection.

The procedure is performed once and is not repeated during the trial.

Follow-up at Week 4

At 4 weeks after the procedure, a follow-up visit will occur to assess safety, including blood tests for general health markers and a specific marker called high sensitivity troponin.

Blood samples will also be collected to measure antibodies against adenovirus type 5.

Any adverse events or side effects will be recorded and evaluated.

Assessment at Week 12

At 12 weeks after the procedure, a comprehensive assessment will be performed.

A treadmill stress test using the modified Bruce protocol will be conducted to measure exercise duration.

A stress imaging test using PET will be performed with 13N-ammonia and flurpiridaz F 18 administered as intravenous injections to assess blood flow to the heart muscle and the extent of areas with reduced blood flow.

The electronic diary data from the 2 weeks prior to this visit will be reviewed to evaluate the frequency and severity of chest pain episodes and nitroglycerin use.

Questionnaires will be completed to assess chest pain classification, quality of life (SAQ score), and general health status (EQ-5D-3L questionnaire).

Blood tests will be performed for safety monitoring, including antibody levels against adenovirus type 5.

Any cardiovascular events, emergency room visits, hospitalizations, or changes in heart-related medications will be recorded.

Assessment at Week 26

At 26 weeks after the procedure, the same comprehensive assessments performed at Week 12 will be repeated.

This includes a treadmill stress test using the modified Bruce protocol.

A stress imaging test using PET with 13N-ammonia and flurpiridaz F 18 administered as intravenous injections.

Review of the electronic diary data from the 2 weeks prior to this visit.

Completion of questionnaires to assess chest pain classification and quality of life.

Blood tests for safety monitoring and antibody levels.

Recording of any cardiovascular events, emergency room visits, hospitalizations, or medication changes.

This marks the end of the main trial period.

Extension period assessment at Week 52

For those participating in the extension period, a final comprehensive assessment will be performed at 52 weeks after the procedure.

All assessments performed at Weeks 12 and 26 will be repeated, including the treadmill stress test, PET stress imaging with 13N-ammonia and flurpiridaz F 18 administered as intravenous injections, electronic diary review, questionnaires, and blood tests.

Any cardiovascular events, emergency room visits, hospitalizations, or medication changes occurring during the extension period will be recorded.

This marks the end of the extension period and the completion of the trial.

Continuous monitoring throughout the trial

Throughout the entire trial period, daily recording of chest pain episodes, their severity, and nitroglycerin use will continue using the electronic diary.

Current medications for chest pain, blood pressure, and cholesterol must remain stable unless changes are medically necessary.

Any side effects, health changes, or cardiovascular events must be reported at each visit.

For 6 months following the Day 1 procedure, appropriate contraception methods must be used if applicable, and donation of eggs or sperm is not permitted during this time.