Clinical Research
assignment
Not Yet Recruiting

Phase 2b Randomized Study of Encoberminogene Rezmadenovec in Refractory Angina Due to Coronary Artery Disease with Flurpiridaz F 18 and 13N-Ammonia

Trial ID
2024-514874-36-01
Protocol
XC001-1002
Sponsor
Xylocor Therapeutics Inc.

Trial statistics

science
3
test molecules
location_city
26
research sites
public
5
countries
medical_information
1
disease
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22
investigators
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5
vendors

Diseases & Conditions

Angina pectoris

Objectives

The primary objective of this study is to evaluate the efficacy of XC001 in subjects with refractory angina. The assessment is based on a composite endpoint consisting of total exercise duration from a graded treadmill test, frequency of angina episodes reported via diary, and ischemic burden measured by positron emission tomography (PET) at 12 and 26 weeks following a single endocardial administration. 5: Efficacy.

Secondary objectives include the evaluation of additional clinical outcomes, such as:

  • Changes in exercise tolerance and ischemic burden (including total myocardial perfusion defect) at 12, 26, and 52 weeks.
  • Impact on angina frequency, severity, CCS functional angina classification, and the requirement for nitroglycerin.
  • Assessment of quality of life using SAQ and EQ-5D-3L questionnaires.
  • Monitoring of modified MACE, which includes cardiovascular death, acute myocardial infarction, revascularization, and hospitalizations related to unstable angina pectoris, acute coronary syndrome, or heart failure.
  • Evaluation of all-cause and cardiovascular mortality.
  • Assessment of the delivery catheter performance and usability.
  • Evaluation of the safety and tolerability of XC001 and the delivery device.
4: Safety.

Participants

This clinical trial involves 25 participants diagnosed with refractory angina due to obstructive coronary artery disease. The study population includes both males and females between the ages of 18 and 85 years. Eligible individuals must have angina pectoris classified as class II-IV according to the CCS Functional Classification and possess a history of reversible left ventricular ischemia. Participants must have a minimum ischemic burden of at least 10% of the left ventricle as assessed by positron emission tomography. Selection requires that the condition is unsuitable for revascularization via coronary artery bypass graft or percutaneous coronary intervention. Subjects must maintain a stable regimen of anti-anginal, anti-hypertensive, and lipid lowering medications. Additionally, participants must agree to specific contraception requirements or restrictions on gamete donation for 6 months following the administration of the investigational product.

Plans and Procedures

This Phase 2b, randomized, double-blind, sham-controlled, multi-center study is designed to evaluate the efficacy and safety of encoberminogene rezmadenovec (XC001) for the treatment of refractory angina due to obstructive coronary artery disease. The research methodology involves a single endocardial administration via catheter. The study protocol consists of a primary period and a 26-week extension. The sequence of study visits begins with a screening visit to assess eligibility, followed by the administration of the investigational product or a sham procedure. Subsequent follow-up assessments occur at 12 and 26 weeks to evaluate the primary composite endpoint, which includes total exercise duration, frequency of angina episodes, and ischemic burden via PET imaging. The extension period continues through 52 weeks to monitor long-term outcomes and safety. Total participant involvement is expected to last up to 52 weeks following the procedure. Early termination from the study may occur based on the adjudication of serious adverse events by an independent data monitoring committee.

Treatment

The experimental treatment consists of encoberminogene rezmadenovec, identified as XC001. This substance is provided as a solution for injection and is administered via a single intracardiac dose of 2.2 ml.

The study includes a sham procedure as a comparator. Additionally, flurpiridaz F 18, a solution for injection, is administered via intravenous administration at a dose of 6.5 mCi. 13N-ammonia, also provided as a solution for injection, is administered via intravenous administration at a dose of 20 mCi.

Efficacy

The efficacy of the investigational product in patients with refractory angina is evaluated using a primary composite endpoint. This endpoint comprises the average of the proportions of subjects achieving a therapy response at week 12 and week 26, compared to a sham procedure. The composite assessment includes total exercise duration (TED) derived from a graded exercise treadmill test (ETT), the frequency of angina episodes recorded via a diary, and ischemic burden assessed through positron emission tomography (PET) stress imaging. All ETT and imaging analyses are conducted by blinded core labs.

Secondary efficacy parameters involve several measures of clinical and physiological response at 12, 26, and 52 weeks. These include:

  • Changes in TED on a Modified Bruce protocol and time-to-angina during ETT.
  • Changes in angina class as measured by the CCS Functional Classification of Angina Pectoris.
  • Relative changes in the frequency, severity, and nitroglycerin use, as well as the number of angina-free days, extracted from an electronic diary.
  • Assessment of coronary flow reserve (CFR) and transmural perfusion deficit (TPD) via PET, including myocardial blood flow (MBF) and myocardial flow reserve (MFR).
  • Changes in time-to-1 mm ST depression on a 12-lead electrocardiogram (ECG) during ETT.
  • Patient-reported outcomes using the SAQ score and the EQ-5D-3L questionnaire.
  • Evaluation of modified MACE, defined as cardiovascular death, acute myocardial infarction (MI), revascularization, or hospitalizations related to acute coronary syndrome (ACS), unstable angina (UAP), or heart failure.
  • Comparison of all-cause mortality and cardiovascular mortality.

Inclusion and Exclusion Criteria

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Inclusion Criteria

  • 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 the 2024 European Society of Cardiology Guidelines for the Management of Chronic coronary syndromes [Vrints et al 2024]).
  • 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. 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.
  • 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
  • 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)
  • Capable of providing informed consent and undergoing all the required tests and procedures in the protocol
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Exclusion Criteria

  • Any of the following: a. a. All 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. Uncontrolled hypercholesterolemia defined as low-density lipoprotein (LDL) above 190 mg/dL. c. Uncontrolled hypertension (systolic blood pressure [BP] >180 mmHg, diastolic BP >100 mmHg) despite maximal medical treatment. d. Current untreated malignant ventricular arrhythmias (with episode of sustained or non-sustained ventricular tachycardia (VT) in last 30 days; suspected/probable/definite). e. Current untreated bradyarrhythmia (<50 bpm) for which a new artificial pacemaker placement is anticipated during the study period. A current pacemaker is allowed. f. 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). g. 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)
  • Patients with unstable chronic obstructive pulmonary disease despite adequate treatment
  • A history or evidence of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV), or active hepatitis B virus (HBV)
  • Severely immuno-compromised patients, including high-dose chronic corticosteroid therapy or cytostatic (oncolytic) therapy
  • 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)
  • 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
  • Pregnancy or currently lactating
  • 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
  • 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
  • Known allergy to nickel

Trial Status by Country

Country Status Start of Recruitment Planned Patients
Belgium BelgiumNot Yet Recruiting03 Nov 20254
Germany GermanyNot Yet Recruiting03 Nov 202520
Hungary HungaryNot Yet Recruiting03 Nov 202520
The Netherlands The NetherlandsNot Yet Recruiting03 Nov 2025—
Poland PolandNot Yet Recruiting03 Nov 202525
Netherlands Netherlands——15

Sites & Investigators

Investigational Products

Details about the medicinal products being studied in this clinical trial.

Product Name Role in Trial Formulation Administration Max Daily Dose Treatment Duration EU MP Number
Ammonia 13N
OtherSOLUTION FOR INJECTIONINTRAVENOUS ADMINISTRATION2024PRD11784403
XC001
TestSOLUTION FOR INJECTIONINTRACARDIAC USE2.21PRD11524855
Flurpiridaz F 18
OtherSOLUTION FOR INJECTIONINTRAVENOUS ADMINISTRATION6.524PRD11789527

Conditions Studied in This Trial

Interventions Studied in This Trial

vaccines
13N-AMMONIA
1 trial

Also investigated for

Angina pectoris 1