A Phase III Prospective, Multicenter, Open-label Study to Assess Diagnostic Efficacy of a Novel 18F-labelled Tracer, SYN2, for Positron Emission Tomography in Subjects with Suspected Coronary Artery Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Synektik S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

25 Jan 2024 → ongoing

Decision date (initial)

2024-06-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Synektik S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

Evaluate diagnostic performance of SYN2 PET MPI in the detection of significant CAD against the reference standard in subjects with suspected CAD.

Secondary objectives 4

1. Diagnostic performance of quantitative perfusion analysis of SYN2 injection PET MPI in the detection of significant CAD against the reference standard in subjects with suspected CAD.
2. To assess the safety of SYN2 PET MPI in the detection of significant CAD in subjects with suspected CAD.
3. Diagnostic performance of qualitative perfusion analysis of SYN2 PET MPI in the detection of significant CAD by ICA alone and defined by >70% stenosis in a major branch in subjects with suspected CAD.
4. Diagnostic performance of quantitative perfusion analysis of SYN2 PET MPI in the detection of significant CAD by ICA alone and defined by >70% stenosis in a major branch in subjects with suspected CAD.

Conditions and MedDRA coding

Coronary Artery Disease

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Male or female, aged over 18 years of age.
4. At the time of enrolment, the subject has been scheduled via written documentation to undergo an invasive coronary angiography for the assessment of CAD.
5. Must be capable of undergoing the pharmacological or exercise stress imaging protocols.
6. For females of reproductive potential: use of sufficiently effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional one week after the last IMP administration. A sufficient contraceptive method includes mechanical barrier (e.g., a male condom or a female diaphragm), combined [estrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal anticonception associated with inhibition of ovulation [oral, injectable, implantable], IUD or IUS. Sexual abstinence is allowed when this is the preferred and usual lifestyle of the subject.
7. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with a partner for 3 months after last IMP exposure.
8. Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout the study duration.

Exclusion criteria 12

1. Subjects who have an established diagnosis of CAD as confirmed by any of the following: a. Previous myocardial infarction (MI); b. Previous coronary revascularization, such as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).
2. Known allergy or hypersensitivity for SYN2 components and other acridine derivatives such as Aminacrine, Ethacridine and Euflavine.
3. Subjects incapable of undergoing pharmacological or exercise cardiac stress testing.
4. Subjects who are unable to undergo all the imaging procedures or who have a current illness or pathology that, in the opinion of the investigator, would pose a significant safety risk for the subject or for whom the participation may compromise the management of other diseases or the investigator judges to be unsuitable for participation in the study.
5. Documented history of heart failure and/or cardiomyopathy and/or prior LV ejection fraction (LVEF) <40%).
6. Subjects with severe valvular disease (Stages C, D defined by 2020 ACC/AHA Guideline).
7. Subjects scheduled for or planning to undergo any cardiac interventional procedures between enrolment and ICA (e.g., balloon angioplasty or bypass surgery).
8. Subjects undergoing evaluation for heart transplantation or with a history of heart transplantation.
9. Subjects who have taken the last dose of an Investigational Medicinal Product (IMP) from another trial within 30 days prior to enrollment in this study, and subjects scheduled to participate in another clinical study during the 7-day follow-up period of this study (except post-marketing observational clinical studies).
10. Female subjects who are pregnant, have a positive (+) pregnancy test, or the possibility of pregnancy cannot be ruled out prior to dosing, or the subject is breastfeeding. The females of childbearing potential must have a negative serum pregnancy test at screening and serum/urine pregnancy test within 4 hours prior to the imaging]
11. Subjects who have a mental or physical condition that prevents them from giving informed consent to participate in a clinical trial.
12. Subjects who have been committed to an institution by virtue of an order issued either by judicial or administrative authorities.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Diagnostic performance in terms of sensitivity and specificity of qualitative expert assessment of SYN2 PET MPI against the reference standard.

Secondary endpoints 4

1. Diagnostic performance in terms of the area under the receiver operating characteristics (AUC-ROC) of quantitative analysis of SYN2 PET MPI against the reference standard in diagnosis of significant CAD. AUC ROC will be estimated by the trapezoidal rule.
2. Adverse events and reportable serious adverse rates during the resting study as defined by the NCI Common Toxicity Criteria for Adverse Events; CTCAE v.5.0, including but not limited to changes in laboratory parameters, ECG parameters, physical examination, and vital signs.
3. Diagnostic performance in terms of sensitivity and specificity of qualitative expert assessment of SYN2 PET MPI in detection of CAD against the reference standard of ICA alone and CAD defined by >70% stenosis in a major branch in subjects with suspected CAD.
4. Diagnostic performance in terms of the area under the receiver operating characteristics (AUC-ROC) of quantitative perfusion analysis of SYN2 PET MPI in the detection of significant CAD by ICA alone and CAD defined by >70% stenosis in a major branch.

Investigational products

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

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Synektik S.A.

Sponsor organisation

Synektik S.A.

Address

Ul. Jozefa Piusa Dziekonskiego 3

City

Warsaw

Postcode

00-728

Country

Poland

Scientific contact point

Organisation

Synektik S.A.

Contact name

Przemysław Kozanecki

Public contact point

Organisation

Synektik S.A.

Contact name

Przemysław Kozanecki

Locations

5 EU/EEA countries · 18 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 27 files

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

Application history

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