Clinical Trials Register

Summary
EudraCT Number:	2014-001351-23
Sponsor's Protocol Code Number:	EGT022-01
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-05-08
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2014-001351-23

A.3

Full title of the trial

A phase IIa, randomized, placebo-controlled, double-blind, parallel study to investigate the efficacy of EG-Mirotin subcutaneously administered in multiple doses on diabetic macular edema in diabetic retinopathy patients.

A.3.1

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

Efficacy Study of EG-Mirotin subcutaneously administered in multiple doses on diabetic macular edema in diabetic retinopathy patients.

II.a fázisú, randomizált, placebo-kontrollos, kettős-vak, párhuzamos vizsgálat a szubkután több adagban alkalmazott EG-Mirotin (EGT022) hatásosságának értékelésére a diabeteses maculaödéma szempontjából, nem proliferatív diabeteses retinopathiában szenvedő betegeknél.

A.4.1

Sponsor's protocol code number

EGT022-01

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	EyeGene, Inc
B.1.3.4	Country	Korea, Republic of
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	EYEGENE
B.4.2	Country	Korea, Republic of
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	EUROFINS OPTIMED
B.5.2	Functional name of contact point	Clarisse Paire project manager
B.5.3	Address:
B.5.3.1	Street Address	1 rue des Essarts
B.5.3.2	Town/ city	Gières
B.5.3.3	Post code	38610
B.5.3.4	Country	France
B.5.4	Telephone number	+330438374761
B.5.5	Fax number	+330438372741
B.5.6	E-mail	clarissepaire@eurofins.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	Information not present in EudraCT
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.3.1	Product name	EG-Mirotin
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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	EGT022-01
D.3.9.3	Other descriptive name	EG-Mirotin
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	1 or 2
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	No
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

diabetic retinopathy patients having early diabetic macular edema (DME)

E.1.1.1

Medical condition in easily understood language

diabetic retinopathy

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

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	10012689
E.1.2	Term	Diabetic retinopathy
E.1.2	System Organ Class	10015919 - Eye 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

Primary objective :
To evaluate the efficacy of EG-Mirotin at doses 1mg and 2mg versus placebo on diabetic macular edema in diabetic retinopathy patients after 5 daily subcutaneous injections. Anatomical efficacy will be assessed by the measurement of central subfield retinal thickness (CSF Thickness) and retinal volume using Spectral Domain-Optical Coherence Tomography (SD-OCT).

E.2.2

Secondary objectives of the trial

Secondary objective :
To evaluate functional efficacy (visual acuity assessed by ETDRS charts)
To evaluate reduction in vascular permeability using measurement of vascular leakage at the time of fluorescein angiography
To evaluate the safety and tolerability of multiple administered dose of EG-Mirotin.
To evaluate the pharmacokinetic of EG-Mirotin at doses 1mg and 2mg after 5 daily subcutaneous administrations.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Systemic :

1. Male/female patient, aged between 18 and 75 years inclusive.
2. Females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control (oral, transdermal, systemic or implant contraception birth control, intrauterine devices, diaphragm or condoms) for the duration of the trial and for 4 months after the last study drug administration. For sexually active male subjects with partners of childbearing potential: accepting to use effective methods of contraception during the study and for 16 weeks after the last drug intake.
3. Females of non-childbearing potential: females must be either surgically sterilized or at least 1 year postmenopausal (amenorrhoea duration at least 12 months).To be eligible for entry into the study, females must have a negative pregnancy test at screening baseline.
4. Patient with type 2 diabetes mellitus with Hb1Ac (glycosylated haemoglobin) ≤ 10%.
5. Body Mass Index (BMI) between 22 and 32 kg/m2 inclusive.
6. Normal blood pressure (BP) and heart rate (HR) at the screening visit after 10 minutes in supine position:
95 mmHg ≤ SBP (systolic blood pressure) ≤ 160 mmHg,
50 mmHg ≤ DBP (diastolic blood pressure) ≤ 95 mmHg,
7. Normal electrocardiogram (ECG) recording on a 12-lead ECG or considered NCs by investigators:
8. Laboratory parameters within the normal range of the laboratory (hematological, blood chemistry tests, urinalysis). Individual values out of the normal range can be accepted if judged clinically non relevant by the Investigator.
9. Having given a written informed consent prior to selection.
10. Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research.
11. Stable antidiabetic treatment for 3 months and for the next 4 months: if needed: metformin and other oral antidiabetics, antihypertensive and drugs to treat dyslipidemiea are allowed.

Ocular within 21 days of randomization :

At least one eye meets the study eye criteria listed below :
12. Best-corrected ETDRS visual acuity letter score between ≥ 79 (approximate Snellen equivalent 20/30 or better) and 24 (approximately 20/320),
13. Non proliferative retinopathy or inactive proliferative retinopathy treated by panretinal photocoagulation dating more than 6 months
14. CSF- thickness measured on spectral domain optical coherence tomography (SD-OCT) of ≥ 305μm in women, and ≥ 320μm in men in the central subfield (average of 2 measurements),
15. Assessment by the treating ophthalmologist that focal photocoagulation (in the study eye) and/or anti-VEGF treatment (in both eyes) could be deferred safely for 4 months
16. Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus imaging;

E.4

Principal exclusion criteria

1. Presence or history of protein drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
2. Allergy to fluorescein
3. Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation.
4. Any drug intake during the last month prior to the first administration except those defined in Section 5.3.
5. Use of anti-platelets drugs
6. Intensive insulin treatment (a pump or more than 3 daily injections)
7. Edema is considered to be due to a cause other than diabetic edema for the chosen eye, especially vitreoretinal interface abnormalities within 1 disc diameter of the fovea (e.g., a taut posterior hyaloid or epiretinal membrane).
8. An ocular condition is present resulting visual acuity would not improve from resolution of edema, at the discretion of the investigator (e.g. foveal atrophy, pigmentary changes, dense subfoveal hard exudates, nonretinal condition) for the chosen eye.
9. An ocular condition is present (others than diabetes) that, in the opinion of the investigator, might affect edema or alter visual acuity during the course of the study (e.g. vein occlusion, uveitis, or other ocular inflammatory disease, neovascular glaucoma…).
10. Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines (i.e. cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal) for the chosen eye.
11. Prior history of intravitreal or peribulbar injections of triamcinolone acetonide or vitrectomy, intravitreal injection of anti-VEGF treatment within the prior 4 months,
12. Prior history of yttrium–aluminum–garnet capsulotomy within the prior 2 months.
13. History of major ocular surgery (cataract or glaucoma surgery, pars plana vitrectomy) in the study eye within prior 4 months or anticipated within the next 4 months following randomization.
14. Prior focal photocoagulation within 4 months before administration
15. Prior panretinal scatter photocoagulation within 6 months before administration or need for a panretinal scatter photocoagulation within the next 4 months (severe pre proliferative diabetic retinopathy or proliferative diabetic retinopathy)
16. Active neovascularization of the disc, retina, iris, or angle, vitreous haemorrhage or tractional retinal detachment for the chosen eye
17. Macular ischemia (>grade 2) on fluorescein angiography
18. General anesthesia within 3 months before administration.
19. Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
20. Positive HBs antigen or anti HCV antibody, or positive results for HIV 1 or 2 tests.
21. Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant, calculated creatinine clearance ≤ 60 mL/min.
22. Blood donation (including in the frame of a clinical trial) within 2 months before administration.
23. Patient who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development.
24. Medical history which in the opinion of the investigator would make the patient unsuitable for participation in the study (including, but not limited, to patients with coronary insuffiency, thromboembolism diseases) .
25. Patient in the exclusion period of a previous study.
26. Patient who cannot be contacted in case of emergency
27. Patient under administrative or legal supervision

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint
Change of CSF-thickness (measured by SD-OCT) and retinal volume on study eye 4 weeks after 5 daily subcutaneous (SC) administrations of EG-Mirotin at doses 1mg and 2mg.

E.5.2

Secondary end point(s)

Secondary endpoints
o Change of CSF-thickness (measured by SD-OCT) and retinal volume on study eye 2 weeks after 5 daily subcutaneous (SC) administrations of EG-Mirotin at doses 1mg and 2mg.
o Assessment of best Corrected ETDRS visual acuity at 2, 4 and 8 weeks.
o Evaluation of vascular leakage (measured by fluorescein angiography) at 4 weeks
o Assessment of stereoscopic funduscopy (grading of diabetic retinopathy) at 2, 4 and 8 weeks
o Change of CSF-thickness (measured by SD-OCT) and retinal volume on fellow eye 2 weeks and 4 weeks after 5 daily subcutaneous (SC) administrations of EG-Mirotin at doses 1mg and 2mg.
o Change of CSF-thickness (measured by SD-OCT) and retinal volume on study eye and contralateral 8 weeks after 5 daily subcutaneous (SC) administrations of EG-Mirotin at doses 1mg and 2mg.
o Assessment of systemic and ocular tolerability and safety,
o Pharmacokinetics assessment : Cmax, Tmax, AUC0-24, AUCt, AUCinf, Kel, t1/2, %AUCextra, Vd, CL.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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)

E.7.1.1

First administration to humans

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

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

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

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	30
F.1.3	Elderly (>=65 years)	Yes
F.1.3.1	Number of subjects for this age range:	30
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	30

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

2017-08-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-28

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2019-04-26

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials