A study to evaluate the safety and effectiveness of a new gene therapy (XC001) for people with coronary artery disease and reduced heart function who are undergoing bypass surgery but may not receive complete blood flow restoration (EXACT-CABG)

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

18 Mar 2026 → 30 Mar 2026

Decision date (initial)

2025-11-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the effects of XC001 versus placebo on residual ischemic burden in participants at risk for incomplete revascularization by coronary artery bypass graft (CABG) surgery as quantified by cardiac cardiovascular magnetic resonance imaging (Adenosine/Regadenoson stress perfusion CMR), including ischemic burden and left ventricular (LV) contractile function.

Secondary objectives 1

1. To evaluate the effect of XC001 versus placebo on CMR variables including cardiac volumes, myocardial scar (volume), global and regional strain (longitudinal, circumferential, radial), and left atrial (LA) volume and function (contractile, reservoir, total), as a measurement of diastolic LV function.

Conditions and MedDRA coding

Chronic angina and left ventricular dysfunction due to coronary artery disease that is considered high risk for incomplete revascularization via coronary artery bypass grafting

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Paul-Ehrlich-Institut

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Males and females, age 18 to 80 years, inclusive, at the time of signing the ICF.
2. 2. Participant has symptomatic multivessel epicardial CAD, and, • Following a decision-making process in the multidisciplinary CV interventional team and the participant, there is a contraindication for a PCI procedure and/or CABG is regarded the best or preferred revascularization method according to locally applicable medical practice guidelines (for Europe: 2024 ESC Guideline for the management of chronic coronary syndromes). • The participant is clinically indicated for surgical coronary revascularization, that is best treated via an elective, stand-alone (i.e., not associated with valve surgery) and on-pump CABG, at high risk for incomplete revascularization (as assessed by local cardiothoracic surgeon and verified by the independent Eligibility Review Committee (ERC)). • Clinically indicated must include the presence of non-acute rest/exertional anginal complaints or its angina-equivalent (typically exertional dyspnea) with a severity equivalent to Canadian Cardiovascular Society (CCS) Angina Class 2-4.
3. 3. LVEF by standard quantitative imaging technique of 25% to 50%.
4. 4. Anatomical findings on coronary angiography and/or stress imaging that increase the likelihood of incomplete revascularization post-CABG and that supply LV segments determined to be ischemic on pre-operative stress imaging (detailed in the ERC Charter). These include, but are not exclusively: a. Diffuse distal coronary artery atherosclerotic disease and/or small coronary target vessels deemed unsuitable for grafting within a major coronary artery b. Multiple segmental lesions along a defined major coronary artery c. In a major coronary artery - “missing vessel” where the vessel is not seen on an angiogram d. Major coronary arteries that are ungraftable due to a long segment of failed stents e. High likelihood of available conduits being insufficient for target lesions in major coronary arteries f. Ischemic regions identified on stress imaging that are not likely to be benefited by CABG (ischemic region greater in size than that portion of myocardium supplied by the target vessel(s) that will likely be successfully grafted). Further detailed in the ERC Charter.
5. 5. All participants 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 participants who are either: a. 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 replacement surgery; OR b. Surgically sterile (i.e., hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) at least 1 month prior to Screening
6. 6. Female participants agree to not donate oocytes and male participants must agree not to donate sperm for 6 months following administration of investigational protocol.
7. 7. Capable of providing informed consent and undergoing all the required tests and procedures in the protocol.

Exclusion criteria 18

1. 1. a. Any emergent cardiovascular condition including acute coronary syndrome, or cerebral vascular accident within the past 60 days prior to the Screening visit; b. Sustained, current systolic blood pressure (BP) less than 90 mmHg or uncontrolled hypertension (systolic BP > 180 mmHg, diastolic BP > 100 mmHg) despite maximal medical treatment; c. Current untreated malignant ventricular arrhythmia; d. Congestive heart failure (HF) within the last 60 days defined as New York Heart Association Functional Class IV; e. Current mitral or aortic valvular heart disease requiring mechanical intervention anticipated during the study period (including percutaneous intervention).
2. 11. Diagnosis of, or treatment for, any cancer within the last 5 years, except for basal or squamous cell carcinoma or carcinomas in situ where surgical excision was considered curative. Past medical history of cancer is not exclusionary as long as the participant has been disease free for at least 5 years since the time of diagnosis and treatment.
3. 12. Known hypersensitivity or any other contraindication to the formulation buffer used to suspend the viral vector or contrast agents (Gadolinium) or vasodilators (Regadenoson or Adenosine) used in any of the radiographic procedures, or contraindication to general anesthesia.
4. 13. Pregnancy or currently lactating.
5. 14. Absolute contraindication to CMR: metallic implant (including pacemaker, or implantable cardioverter defibrillator), uncontrolled claustrophobia, severe renal dysfunction (eGFR<30 mL/minute/1.73 m2), or on renal dialysis.
6. 15. Recurrent or persistent atrial fibrillation with rapid ventricular response (>100 bpm) that precludes the analysis of CMR stress imaging (to assess ischemic burden, cardiac dimensions and cardiac function).
7. 16. Receiving an investigational intervention or participating in another clinical study within 30 days or within 5 half-lives (whichever is longer) of the drug prior to Screening. An exception may be made if the individual is enrolled in a nontherapeutic observational study (registry) or the observational portion of a therapeutic study where the sponsoring authority authorizes enrollment.
8. 17. Prior participation in any gene therapy; however, if the study was unblinded or documentation otherwise exists that the participant was randomized to the placebo control group and did not receive active gene transfer agent, the participant may be considered for this study.
9. 18. Has a serious or unstable medical (including unstable chronic obstructive pulmonary disease under adequate treatment) or psychological condition (including drugs or alcohol abuse) that, in the opinion of the Investigator (with input from the ERC as appropriate), would compromise the participant’s safety or successful participation in the study or interpretation of study results
10. 3. Participants with uncontrolled coagulation disorder (that cannot be corrected by pharmacotherapy).
11. 4. Participants with documented, active proliferative retinopathy from any cause (ETDRS [Early Treatment Diabetic Retinopathy Study] score >35).
12. 5. Indication for combination of CABG with any valvuloplasty or valvular replacement and/or arrhythmia surgery (for instance a Cox-maze IV surgical procedure for atrial fibrillation).
13. 6. Body mass index (BMI) > 45 kg/m2.
14. 7. Hemoglobin < 10 g/dL, absolute neutrophil count < 1.5 × 10^3 per μL, platelet count < 75,000 per μL, alanine aminotransferase and aspartate aminotransferase > 3 × upper limit of normal (ULN), total bilirubin > 2 × ULN unless the participant has a previously known history of Gilbert’s syndrome
15. 8. Diabetic individuals with glycosylated hemoglobin (HbA1c) > 9.5% or with active proliferative diabetic retinopathy.
16. 9. A history or evidence of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV), active hepatitis B virus (HBV).
17. 10. Severely immune compromised participants, including participants currently treated with chronic high dose of corticosteroid therapy and/or cytostatic (oncolytic) therapy.
18. 2. Anti-angiogenic therapies, including agents such as Nintedanib that may be prescribed for nononcologic indications (e.g., interstitial lung disease).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline (post-CABG at Day 4-6) in treated segment(s) comparing XC001 and placebo in CMR imaging parameters at Weeks 12 and 26 post-surgery. The endpoint at the participant level is the proportion of qualifying segments that improve at 12 and/or 26 weeks as determined by myocardial ischemic burden (see details in the Protocol).

Secondary endpoints 1

1. Change from Baseline (post-CABG at Day 4-6) in treated segment(s) comparing XC001 and placebo in CMR parameters at 12 and 26 weeks, as well as at 52 weeks (during the extension period) (unless stated otherwise). Baseline CMR is defined as CMR analysis at Day 4-6 post-CABG (see details regarding CMR parameters in the Protocol).

Investigational products

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

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Xylocor Therapeutics Inc.

Sponsor organisation

Xylocor Therapeutics Inc.

Address

411 Swedeland Road Suite 23-1080

City

King Of Prussia

Postcode

19406-2787

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 8

Locations

4 EU/EEA countries · 13 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 41 files

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

Application history

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