ENCOBERMINOGENE REZMADENOVEC for Refractory angina pectoris | Coronary artery disease

Inclusion criteria

• {"criterion_text":"- Males and females, age 18 to 85 years, inclusive, at the time of signing the ICF\n- Female subjects agree to not donate oocytes and male subjects must agree not to donate sperm for 6 months following administration of the investigational product (IP)\n- Capable of providing informed consent and undergoing all the required tests and procedures in the protocol\n- 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 the 2024 European Society of Cardiology Guidelines for the Management of Chronic coronary syndromes [Vrints et al 2024]).\n- Angina class II-IV as measured by CCS Functional Classification of Angina Pectoris\n- 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. Participant must have a minimum ischemic burden defined as at least 10% ischemic area (2 segments) of the left ventricule noted on the baseline/screening PET as assessed by the core lab.\n- 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\n- Two baseline ECG stress tests (treadmill test, modified Bruce protocol) that adhere to the following (details outlined in the ETT manual): i.\tA modified Bruce protocol that includes two three-minute warm-up stages of 1.7 mph/ 0% grade and 1.7 mph/ 5% grade. ii.\tTED of 90 seconds to 9.5 minutes that is limited/stopped because of angina (or angina equivalent). iii.\tThe 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.\tThe tests must be performed at least 48 hours apart from each other. v.\tA third test is permitted if the second test does not meet the criteria\n- 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\n- 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)\n- 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: •\tPostmenopausal (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 •\tSurgically sterile (i.e., hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) at least 1 month prior to Screening"}

Exclusion criteria

• {"criterion_text":"- Any of the following: a.\ta.\tAll acute coronary syndrome (including ST-elevation or non-ST elevation myocardial infarction [STEMI or NSTEMI] not requiring revascularization, transmural MI), and cerebral vascular accidents within the past 60 days prior to the screening visit. b.\tUncontrolled hypercholesterolemia defined as low-density lipoprotein (LDL) above 190 mg/dL. c.\tUncontrolled hypertension (systolic blood pressure [BP] >180 mmHg, diastolic BP >100 mmHg) despite maximal medical treatment. d.\tCurrent untreated malignant ventricular arrhythmias (with episode of sustained or non-sustained ventricular tachycardia (VT) in last 30 days; suspected/probable/definite). e.\tCurrent untreated bradyarrhythmia (<50 bpm) for which a new artificial pacemaker placement is anticipated during the study period. A current pacemaker is allowed. f.\tCongestive 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). g.\tAnginal episodes that routinely require the administration of opiates\n- A history or evidence of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV), or active hepatitis B virus (HBV)\n- Severely immuno-compromised patients, including high-dose chronic corticosteroid therapy or cytostatic (oncolytic) therapy\n- Diagnosis of, or treatment for, any cancer within the last 5 years except for cutaneous basal or squamous cell carcinoma or carcinomas in situ where surgical excision was considered curative. (Past medical history of cancer is not exclusionary if the subject has been disease free for at least 5 years since the end of treatment)\n- Known hypersensitivity or any other contraindication to adenosine, regadenoson, or contrast agents used in any of the radiographic procedures or contraindication to anesthesia employed for the study procedure\n- Pregnancy or currently lactating\n- Receiving an investigational intervention or participating in another clinical trial within 30 days or within 5 half-lives of the drug prior to screening. Exception may be made if the individual is enrolled in a non-therapeutic observational study (registry) or the observational portion of a therapeutic study where the sponsoring authority authorizes enrollment\n- Prior participation in any gene therapy; however, if the study was unblinded or documentation otherwise exists that the subject was randomized to the placebo control group and did not receive active gene transfer agent, the subject may be considered for this study. Has a serious or unstable medical or psychological condition (including drug or alcohol abuse) or other circumstance that, in the opinion of the investigator or ERC, would compromise the subject’s safety or successful participation in the study or interpretation of study results. In particular, any suspected drug-seeking behavior related to chest pain should be exclusionary\n- Known allergy to nickel\n- 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\n- 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\n- Body mass index > 45 kg/m2\n- 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\n- Diabetic with current glycosylated hemoglobin (HbA1c) > 9.5% or active proliferative diabetic retinopathy\n- Documented active proliferative retinopathy from any cause (ETDRS [Early Treatment Diabetic Retinopathy Study] score >35)\n- Uncontrolled coagulation disorder (that cannot be corrected by pharmacotherapy)\n- Patients with unstable chronic obstructive pulmonary disease despite adequate treatment"}

Primary endpoints

• {"endpoint_text":"- (Part 2 only) The primary composite endpoint is the average of the proportions of subjects with a therapy response at Week 12 and the proportion of subjects with a therapy response at Week 26 for XC001, as compared to the sham procedure group. All ETT and imaging analysis will be assessed by blinded core labs.","definition_or_measurement_approach":"Composite comprises: a) total exercise duration (TED) from a graded treadmill test (ETT) as assessed by a core lab, b) angina episodes from a diary (extracting the 2 weeks prior to the Week 12 and Week 26 visit), and c) ischemic burden from stress PET as assessed by a core lab. All ETT and imaging analyses are evaluated by blinded core laboratories."}

Secondary endpoints

• {"endpoint_text":"- (Part 2 only) Difference in percentage of subjects with a therapy response as compared to the sham procedure group (each timepoint will be analyzed separately) at 12 and 26 weeks separately, as well as at 52 weeks in the extension period","definition_or_measurement_approach":"Proportion difference in therapy response at each timepoint (12, 26, and 52 weeks in extension) comparing XC001 vs sham; timepoints analysed separately."}
• {"endpoint_text":"- (Part 2 only) Average of changes from baseline to 12 and 26 weeks, as well as at week 52 in the extension period, as compared to sham procedure in TED on a Modified Bruce protocol ETT","definition_or_measurement_approach":"Change in total exercise duration (TED) on Modified Bruce protocol treadmill ETT from baseline to weeks 12 and 26 (and week 52 extension), compared to sham; ETT reviewed by core lab."}
• {"endpoint_text":"- (Part 2 only) Change from baseline to 12 and 26 weeks (as well as to week 52 in the extension period) as compared to sham procedure in TED on a Modified Bruce protocol","definition_or_measurement_approach":"Absolute change in TED on Modified Bruce protocol treadmill test at specified timepoints versus sham."}
• {"endpoint_text":"- (Part 2 only) Change from baseline (% relative change) to 12 and 26 weeks separately, (as well as to the week 52 in the extension period) as compared to sham procedure in the frequency of angina episodes, severity and nitroglycerin (NTG) use over a 2-week observation period (The 2-week time period prior to Week 12 and 26 will be extracted from the daily collection of angina episodes and nitroglycerin use)","definition_or_measurement_approach":"Relative % change from baseline in angina episode frequency, severity and NTG use measured over 2-week windows prior to Week12 and Week26 (extracted from daily electronic diary entries)."}
• {"endpoint_text":"- (Part 2 only) Change from baseline (% relative change) to 12 and 26 weeks (as well as to week 52 in the extension period) as compared to sham control procedure in regional CFR and TPD as measured by PET (including MBF and myocardial flow reserve [MFR])","definition_or_measurement_approach":"PET-derived measures: change in regional coronary flow reserve (CFR), total perfusion defect (TPD), myocardial blood flow (MBF) and myocardial flow reserve (MFR) from baseline to timepoints, compared to sham; assessed by core lab."}
• {"endpoint_text":"- (Part 2 only) Change from baseline to Weeks 12, and 26 (as well as to week 52 in the extension period) as compared to sham procedure in angina class as measured by the CCS Functional Classification of Angina Pectoris","definition_or_measurement_approach":"Change in CCS angina functional class from baseline at specified timepoints compared to sham."}
• {"endpoint_text":"- (Part 2 only) Change from baseline to weeks 12 and 26 (as well as to week 52 in the extension period) as compared to sham procedure in time-to-angina during the Modified Bruce protocol ETT","definition_or_measurement_approach":"Time-to-angina on Modified Bruce protocol ETT compared from baseline to timepoints versus sham (ETT assessed per protocol/core lab)."}
• {"endpoint_text":"- (Part 2 only) Change from baseline to weeks 12 and 26 ( as well as to week 52 in the extension period) in time-to-1 mm ST depression on ETT 12lead ECG","definition_or_measurement_approach":"Time-to-1 mm ST depression on 12-lead ECG during ETT compared to baseline and between arms at timepoints."}
• {"endpoint_text":"- (Part 2 only) Change from baseline to weeks 12 and 26 (as well as to week 52 in the extension period) as compared to sham procedure in the use of anti-anginal agents and the quantity and frequency of use of prophylactic/as needed (prn) nitroglycerin (% relative change)","definition_or_measurement_approach":"Relative % change from baseline in use, quantity and frequency of anti-anginal medications and prophylactic/PRN nitroglycerin use, compared to sham."}
• {"endpoint_text":"- (Part 2 only) Change from baseline to weeks 12 and 26 (as well as to week 52 in the extension study) as compared to sham procedure in SAQ score and in the EQ-5D-3L questionnaire","definition_or_measurement_approach":"Change from baseline in SAQ (Seattle Angina Questionnaire) scores and EQ-5D-3L health-related quality of life questionnaire scores versus sham at timepoints."}
• {"endpoint_text":"- (Part 2 only) Change from baseline up to weeks 12 and 26 (as well as up to week 52 in the extension period) as compared to sham procedure in modified MACE frequency. Modified MACE is defined as any cardiovascular death, acute MI, any revascularization procedure, emergency room (ER) visits or hospitalization due to acute coronary syndrome (ACS), unstable angina (UAP), or heart failure","definition_or_measurement_approach":"Change in frequency of modified MACE (composite defined in text) from baseline to timepoints compared to sham."}
• {"endpoint_text":"- (Part 2 only) Change from baseline up to weeks 12 and 26 (as well as up to week 52 in the extension period) compared to sham procedure in time to first modified MACE","definition_or_measurement_approach":"Time-to-first modified MACE from baseline compared between XC001 and sham."}
• {"endpoint_text":"- (Part 2 only) Comparison of all-cause and cardiovascular mortality between the treatment group and the sham group up to weeks 12 and 26 (as well as up to week 52 in the extension period)","definition_or_measurement_approach":"Comparison of all-cause and CV-specific mortality rates between arms up to specified timepoints."}
• {"endpoint_text":"- (Part 2 only) Change from baseline up to weeks 12 and 26 of daily angina frequency (% relative change), angina severity, sublingual (sl) nitroglycerin use and number of angina-free days using an electronic diary","definition_or_measurement_approach":"Daily electronic diary-derived metrics: angina frequency, severity, SL nitroglycerin use and angina-free days; % relative change from baseline compared between arms."}
• {"endpoint_text":"- (Part 2 only) To evaluate device handling, performance, and usability of the delivery catheter (Extroducer®) during the delivery procedure","definition_or_measurement_approach":"Assessment of device handling, performance and usability of Extroducer catheter during administration procedure (procedural assessments collected during Part 2)."}
• {"endpoint_text":"- Safety Endpoints (Part 1 and Part 2): Investigational Product - Safety through Week 26 (as well as through week 52 in the extension period). All drug-related SAEs up to 26 weeks (and 52 weeks in the extension period) post-procedure as adjudicated by IDMC.","definition_or_measurement_approach":"Collection and adjudication by IDMC of all drug-related serious adverse events through Week 26 (and through Week 52 in extension). Safety labs and adjudications per protocol."}
• {"endpoint_text":"- Safety Endpoints (Part 1 and Part 2): Investigational Device - All investigational device-related TESAEs up to 4 weeks post-procedure (i.e., serious adverse device effects) as adjudicated by IDMC.","definition_or_measurement_approach":"Collection and IDMC adjudication of investigational device-related TESAEs up to 4 weeks post-procedure."}
• {"endpoint_text":"- Safety Endpoints (Part 1 and Part 2): Additional safety endpoints - AE’s (including trends as identified by IDMC); hematology; clinical chemistry (including high sensitivity troponin), and anti-Ad5 neutralizing antibodies and","definition_or_measurement_approach":"Additional safety measures include adverse events (including IDMC-identified trends), hematology, clinical chemistry including high-sensitivity troponin, and anti-Ad5 neutralizing antibody assessments per protocol."}

Poland

Earliest CTIS Part Ii Submission Date

10-10-2025

Latest Decision Or Authorization Date

07-11-2025

Processing Time Days

28

Number Of Sites

8

Number Of Participants

25

Hungary

Earliest CTIS Part Ii Submission Date

12-09-2025

Latest Decision Or Authorization Date

10-11-2025

Processing Time Days

59

Number Of Sites

8

Number Of Participants

20

Belgium

Earliest CTIS Part Ii Submission Date

17-10-2025

Latest Decision Or Authorization Date

04-11-2025

Processing Time Days

18

Number Of Sites

2

Number Of Participants

4

Netherlands

Earliest CTIS Part Ii Submission Date

11-10-2025

Latest Decision Or Authorization Date

05-11-2025

Processing Time Days

25

Number Of Sites

6

Number Of Participants

15

Germany

Earliest CTIS Part Ii Submission Date

08-10-2025

Latest Decision Or Authorization Date

07-11-2025

Processing Time Days

30

Number Of Sites

2

Number Of Participants

20

Primary sponsor

Full Name

Xylocor Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Everest Clinical Research Corporation

Responsibilities

Data management, Biostatistics and other study operational responsibilities (sponsorDuties codes listed in submission)

Name

Signant Health LLC

Responsibilities

ePRO diaries and related electronic data capture responsibilities

Third parties

• {"country":"United States","full_name":"The Brigham And Women’s Hospital Inc.","duties_or_roles":"Core Laboratory for PET Imaging","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"Multiple sponsor duties (codes provided in submission); listed value: Data management, Biostatistics","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"ePRO diaries (electronic patient-reported outcome diaries) plus other sponsor duty codes","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Central laboratory services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Saint Louis University","duties_or_roles":"Core Laboratory for Exercise Tolerance Test and ECGs","organisation_type":"Educational Institution"}