An investigational trial to evaluate the effects of the drug XC001 delivered via a catheter in subjects with chronic angina caused by coronary artery disease (EXACT-2 Trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Xylocor Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

17 Apr 2026 → ongoing

Decision date (initial)

2025-11-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

XyloCor Therapeutics, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

(Part 2 only) To evaluate the effect of XC001 on a composite endpoint of 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 imaging by PET (as assessed by a core lab) at 12 and 26 weeks following a one-time endocardial administration to subjects with RA compared to the sham procedure.

Secondary objectives 8

1. (Part 2 only) To evaluate the effect of XC001 on exercise tolerance (total exercise duration on a treadmill exercise tolerance test) at 12 and 26 weeks, as well as at 52 weeks in the extension period compared to the sham procedure.
2. (Part 2 only) To evaluate the effect of XC001 on ischemic burden by PET at 12 and 26 weeks, as well as at 52 weeks in the extension period. (including total myocardial perfusion defect) compared to the sham procedure
3. (Part 2 only) To evaluate the effect of XC001 on angina frequency, severity and nitroglycerin use at 12 and 26 weeks, as well as at 52 weeks in the extension period compared to the sham procedure
4. (Part 2 only) To evaluate the effect of XC001 on CCS functional angina classification at 12 and 26 weeks compared to the sham procedure
5. (Part 2 only) To evaluate the effect of XC001 compared to the sham procedure on the changes from baseline to 12, and 26 weeks (as well as at 52 weeks in the extension period): • Time to angina during the ETT (modified Bruce protocol), • Time-to-1 mm ST depression on a treadmill exercise test (modified Bruce protocol), • Use of antianginal agents, including sublingual (sl) nitroglycerin, • Quality of life (QoL)- SAQ scores and EuroQol 5-Dimension 3-Level (EQ-5D-3L) questionnaires • Frequency of modified MACE compared to the sham procedure, as well as up to 52 weeks in the extension period. Modified MACE is defined as any cardiovascular death, acute MI, any revascularization procedure, emergency room (ER) visits or hospitalization due to unstable angina pectoris (UAP), due to acute coronary syndrome (ACS), or due to heart failure. • Time to the first modified MACE from baseline up to week 12, and up to 26, (as well as up to week 52 in the extension period). • All-cause and cardiovascular mortality between the treatment group and the sham group up to week 12, and up to 26, (as well as up to week 52 in the extension period). • Daily angina frequency, severity and nitroglycerin use, and number of angina-free days using an electronic diary up to 12 and 26 weeks.
6. (Part 2 only) To evaluate device handling, performance, and usability of the delivery catheter (Extroducer®) during the delivery procedure.
7. Safety Objectives (Part 1 and Part 2): To evaluate the safety and tolerability of XC001 through 26 weeks (as well as up to 52 weeks in the extension period).
8. Safety Objectives (Part 1 and Part 2): To evaluate the safety of the delivery catheter (Extroducer®) up to 4 weeks after the assigned study procedure (Day 1)

Conditions and MedDRA coding

Refractory angina due to obstructive coronary artery disease

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Paul-Ehrlich-Institut

Plan to share IPD

No

IPD plan description

Not applicable

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Males and females, age 18 to 85 years, inclusive, at the time of signing the ICF
2. 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]).
3. Angina class II-IV as measured by CCS Functional Classification of Angina Pectoris
4. 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.
5. 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
6. 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
7. 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
8. 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)
9. 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
10. 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)
11. Capable of providing informed consent and undergoing all the required tests and procedures in the protocol

Exclusion criteria 17

1. 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
2. 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
3. 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
4. Body mass index > 45 kg/m2
5. 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
6. Diabetic with current glycosylated hemoglobin (HbA1c) > 9.5% or active proliferative diabetic retinopathy
7. Documented active proliferative retinopathy from any cause (ETDRS [Early Treatment Diabetic Retinopathy Study] score >35)
8. Uncontrolled coagulation disorder (that cannot be corrected by pharmacotherapy)
9. Patients with unstable chronic obstructive pulmonary disease despite adequate treatment
10. A history or evidence of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV), or active hepatitis B virus (HBV)
11. Severely immuno-compromised patients, including high-dose chronic corticosteroid therapy or cytostatic (oncolytic) therapy
12. 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)
13. 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
14. Pregnancy or currently lactating
15. 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
16. 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
17. Known allergy to nickel

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. (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.

Secondary endpoints 18

1. (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
2. (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
3. (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
4. (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)
5. (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])
6. (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
7. (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
8. (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
9. (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)
10. (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
11. (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
12. (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
13. (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)
14. (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
15. (Part 2 only) To evaluate device handling, performance, and usability of the delivery catheter (Extroducer®) during the delivery procedure
16. 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.
17. 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.
18. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Xylocor Therapeutics Inc.

Sponsor organisation

Xylocor Therapeutics Inc.

Address

1200 Liberty Ridge Drive

City

Chesterbrook

Postcode

19087-5563

Country

United States

Scientific contact point

Organisation

Xylocor Therapeutics Inc.

Contact name

Dawn Byrnes

Public contact point

Organisation

Xylocor Therapeutics Inc.

Contact name

Dawn Byrnes

Third parties 5

Locations

5 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 93 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications