Clinical Trials Register

Summary
EudraCT Number:	2019-003087-43
Sponsor's Protocol Code Number:	SAFER
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-08-06
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2019-003087-43

A.3

Full title of the trial

A Phase I/II Seamless Adaptive, Open label study to assess Safety, Tolerability, Radiation Dosimetry, Biodistribution, and diagnostic ability of a Novel 18F-labelled Tracer, SYN2, for Positron Emission Tomography in Myocardial Perfusion Imaging (SAFER) in Healthy Volunteers (phase I) and patients with suspected Coronary Artery Disease (phase II)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.4.1

Sponsor's protocol code number

SAFER

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Synektik Spółka Akcyjna
B.1.3.4	Country	Poland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Synektik Spółka Akcyjna
B.4.2	Country	Poland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Clinscience Sp. z o.o.
B.5.2	Functional name of contact point	CRO company
B.5.3	Address:
B.5.3.1	Street Address	ul. Racławicka 146
B.5.3.2	Town/ city	Warszawa
B.5.3.3	Post code	02-117
B.5.3.4	Country	Poland
B.5.4	Telephone number	+48789 803 620
B.5.6	E-mail	karolina.olewnik@clinscience.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	SYN2
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravascular use (Noncurrent) Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	Yes
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	SYN2
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravascular use (Noncurrent) Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	Yes
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

phase II: suspected coronary artery disease

E.1.1.1

Medical condition in easily understood language

suspected coronary artery disease

podejrzenie choroby niedokrwiennej serca

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10011078
E.1.2	Term	Coronary artery disease
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Phase I:
To assess safety and tolerability of a single dose of SYN2 in healthy volunteers

Phase II:
To assess safety and tolerability of SYN2 in patients with suspected CAD and referral to ICA.

E.2.2

Secondary objectives of the trial

Phase I:
To determine distribution of 18F after i.v. administration of SYN2 to calculate internal radiation dosimetry and the effective dose in healthy subjects.
To assess pharmacokinetics of SYN2 to determine a mathematical model for a software used for quantitation of myocardial perfusion.

Phase II:
To assess diagnostic ability of Myocardial Perfusion Imaging with SYN2 in patients with suspected CAD and referral to ICA.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Phase I
Inclusion Criteria
1. Must be willing and able to provide signed written informed consent prior to any study related procedures;
2. Male or Female, over 18 years of age;
3. Body mass index < 30 kg/m2
4. Normal or clinically acceptable medical history, physical examination, ECG, and vital signs findings during the screening period as determined by the investigator.
5. Must have a serum creatinine within the normal limits investigational site's normal range.
6. Must have liver function tests < 1.5 times the investigational site's normal range.
7. Must have a haematocrit level within 5% of the investigational site's normal range.
8. Willingness to abstain sexual intercourse at least 24 hours before and after the tracer administration
9. Willingness to practice effective contraception for 3 months after the tracer administration
10. Negative test results for drugs of abuse and alcohol at screening and on the day of tracer administration/PET imaging

Phase II
Inclusion Criteria:
1. Must be willing and able to provide signed written informed consent prior to any study related procedures;
2. Male or Female, over 18 years of age;
3. At the time of enrolment, the patient has been scheduled via written documentation to undergo an angiography for the assessment of CAD. This includes the existence of an annotation in the patient's record (medical history) of the need for or planned ICA in the patient. Moreover, it is allowed for a patient to be referred to the ICA during the enrollment period, and not before signing the informed consent to participate in the study.
4. The patient has undergone a clinically indicated SPECT MPI study within 180 days before informed consenting OR the patient is willing to undergo SPECT MPI study for the purposes of this clinical study. . As an alternative to SPECT a PET-CT imaging with 13N-ammonia will be performed. Collected data will serve as a gold-standard to improve an images quality, assessed on the dedicated software. The PET-CT with 13N-ammonia will be performed only if neither the SPECT nor the PET-CT with 13N-ammonia scan were done within 180 days before informed consenting. The PET-CT with 13N-ammonia will be required for a minimum of 4 patients.
5. The subject is able and willing to comply with all study procedures as described in the protocol.
6. Willingness to abstain sexual intercourse at least 24 hours before and after the tracer administration
7. Willingness to practice effective contraception for 3 months after the tracer administration

E.4

Principal exclusion criteria

Phase I:
Exclusion Criteria:
1. Any clinically significant acute or chronic unstable physical or psychological disease based on medical history or screening physical examination;
2. Any clinically significant abnormality in the screening laboratory tests or ECG;
3. Any exposure to any investigational drugs within four (4) weeks prior to Visit 1;
4. Any exposure to investigational radiopharmaceuticals within 12 months prior to the date of Visit 1;
5. Any new prescription medications within four (4) weeks of Visit 1;
6. Subject has a positive (+)pregnancy test, the possibility of pregnancy cannot be ruled out prior to dosing, or the subject is breast-feeding.
7. Subject has experienced any allergic reaction to similar compounds or agents.
8. Subject has a positive SARS-CoV-2 test result on screening.

Phase II:
Exclusion Criteria:
1. Patients who are unable to undergo all the imaging procedures based on the investigators opinion. Reasons may be any clinically significant acute or unstable physical or psychological disease judged by the investigators based on medical history or screening physical examination.
2. Patients who have an established diagnosis of CAD as confirmed by any of the following:
a. Previous myocardial infarction (MI);
b. Previous cardiac catheter angiography showing ≥50% stenosis;
c. Previous coronary revascularisation, such as percutaneous coronary intervention (PCI), thrombolysis or coronary artery bypass graft (CABG) placement.
3. Patients incapable of undergoing pharmacological cardiac stress testing.
4. Patients who have a current illness or pathology that, in the opinion of the investigator, would pose a significant safety risk for the patient during cardiac stress testing.
5. Documented history of heart failure and/or cardiomyopathy and/or prior LV ejection fraction (LVEF) <50%).
6. Patients scheduled for or planning to undergo any cardiac interventional procedures between enrolment and ICA (e.g. balloon angioplasty or bypass syrgery).
7. Patients without abnormalities in the SPECT MPI or in the PET-CT with 13N-ammonia performed at screening visit (V0). Any SPECT or PET-CT with 13N-ammonia abnormality is the basis for patient enrollment in the study. All factors must be taken into account, both (symptoms and signs) exercise tolerance, changes in the ECG, the picture of cardiac prefusion, etc.
8. Patients undergoing evaluation for heart transplantation or with history of heart transplantation.
9. Patients enrolled in another clinical study within the 30 days prior to being enrolled in this study or scheduled to participate in another clinical study during the 7-day follow-up period of this study
10. Female subject has a positive (+) pregnancy test, the possibility of pregnancy cannot be ruled out prior to dosing, or the subject is breast-feeding.
11. Subject has a positive SARS-CoV-2 test result on screening.

E.5 End points

E.5.1

Primary end point(s)

Phase I:
Adverse events and reportable serious adverse 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, vital signs, volunteer reported events.
P
hase II:
Adverse events and reportable serious adverse 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, vital signs.

E.5.1.1

Timepoint(s) of evaluation of this end point

Phase I:
screening,
day-1,
Days 1 to 3,
48 h (±8 h) post dose;
5 days (±2 days) post-dose
14 days (±2 days) post-dose

Phase II:V0, V1, V2,V3,V4
V0-Screening, V1, V2, V3

E.5.2

Secondary end point(s)

Phase I:
Internal radiation dose and the effective dose as well as biodistribution of the SYN2 in healthy subjects.
Data on kinetic behaviour of SYN2 in heart and circulation as well as on SYN2 metabolites.

Phase II:
Diagnostic ability of SYN2 in the detection of CAD using ICA with FFR as the reference standard.

E.5.2.1

Timepoint(s) of evaluation of this end point

Phase I: Day 1
Phase II: V1, V2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Since the study has only a diagnostic objective, patients who complete the study will continue their treatment with their specialist physician.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-01-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-10-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-02-23

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