Clinical Trials Register

Summary
EudraCT Number:	2019-000642-35
Sponsor's Protocol Code Number:	HL217-201
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-02-04
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

France - ANSM

A.2

EudraCT number

2019-000642-35

A.3

Full title of the trial

A phase IIa randomized, double-blind, multicentre study to evaluate safety and efficacy of HL217 topical ophthalmologic solution in the treatment of exudative Age-Related Macular Degeneration (AMD)

A.4.1

Sponsor's protocol code number

HL217-201

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	HANLIM PHARM CO., LTD
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	HANLIM PHARM CO., LTD
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	Fanny KAYSER, 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	+330438372566
B.5.5	Fax number	+330438372741
B.5.6	E-mail	aecoptimed@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	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.3.1	Product name	HL217
D.3.4	Pharmaceutical form	Eye drops
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	571141-49-6
D.3.9.2	Current sponsor code	HL217
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	EYLEA
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer AG
D.2.1.2	Country which granted the Marketing Authorisation	France
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	aflibercept
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraocular 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	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	Eye drops, solution
D.8.4	Route of administration of the placebo	Ocular use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Injection
D.8.4	Route of administration of the placebo	Intravitreal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

AMD (age-related macular degeneration)

E.1.1.1

Medical condition in easily understood language

age-related macular degeneration

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	LLT
E.1.2	Classification code	10068530
E.1.2	Term	Macular degeneration progression
E.1.2	System Organ Class	100000004853

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate efficacy of HL217 after multiple eye drop administrations in patients with exudative AMD by measuring macular thickness from D1 to D84 (3 months).

E.2.2

Secondary objectives of the trial

1. Efficacy : evaluation of HL217 efficacy in each group from D1 to D14, D28, D56 and D84.

2. Safety : evaluation of safety in each group from D1 to D14, D28, D56 and D84.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and menopaused women patients, aged 50 years or more;
2. Active subfoveal choroidal neovascularization (CNV) due to Age-related Macular Degeneration (AMD) in the study eye diagnosed using fluorescein and indocyanine green angiography and SD-OCT, total lesion ≤12 Macular Photocoagulation Study (MPS) disc areas or ≤30,48 mm², with the active lesion (excluding fibrosis and subretinal hemorrhage) should be ≥50% of the total lesion size.
3. Intraretinal or subretinal fluid due to choroidal neovascularization (CNV) visible on SD-OCT;
4. Best-corrected Visual Acuity (BCVA) between 78 and 14 letters, inclusive, in the study eye at the screening/randomization visit using Early Treatment Diabetic Retinopathy Study (ETDRS) testing, with BCVA decrement primarily attributable to neovascular Age-related Macular Degeneration (AMD);
5. Treatment naive (i.e., no previous anti-vascular endothelial growth factor [VEGF] treatment in the study eye);
6. Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus imaging;
7. Willing and able to return for all study visits;
8. Able to adhere to the study protocol and its requirements;
9. Signing 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.

E.4

Principal exclusion criteria

1. Non-study eye best corrected visual acuity (BCVA) worse than 20 letters at the screening/randomization visit using Early Treatment Diabetic Retinopathy Study (ETDRS) testing;
2. Choroidal neovascularization (CNV) in the study eye secondary to other causes (e.g., pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, posterior uveitis, or multifocal choroiditis);
3. Polypoidal choroidal vasculopathy (PCV) The diagnosis of PCV required either the presence of elevated orange-red lesions observed at the fundus or the presence of charac- teristic polypoidal vascular lesions by ICGA).
4. Previous macular laser photocoagulation or ocular photodynamic therapy in the study eye;
5. Media opacities or abnormalities in the study eye that would preclude visualization of the retina;
6. Other retinal diseases in the study eye that would interfere with vision; including: retinal pigment epithelial (RPE) tear, subretinal haemorrhage (including the fovea);
7. Uncontrolled glaucoma or ocular hypertension in the study eye defined as an Intraocular Pressure (IOP) > 30 millimeters of mercury (mmHg) regardless of concomitant treatment with IOP lowering medications;
8. Previous pars plana vitrectomy in the study eye;
9. Any intraocular surgery in the study eye within 90 days (3 months) prior to study enrolment;
10. Yttrium aluminium garnet (YAG) laser treatment in the study eye within 30 days (1 month) prior to study enrolment;
11. Intravitreal/periocular ocular steroids (dexamethasone implant or triamcinolone injection) in the study eye within 90 days (3 months) prior to study enrolment;
12. Topical or subconjunctival injection of steroid (except triamcinolone) in the study eye within 15 days;
13. Concomitant use of any topical ophthalmic medications in the study eye, including glaucoma medications, unless on a stable dose for at least 90 days (3 months) prior to study enrolment and expected to stay on stable dose throughout study participation. Artificial tears are allowed but not ointments;
14. Chronic or recurrent uveitis in the study eye, ongoing ocular infection or inflammation in either eye;
15. A history of cataract surgery complicated by vitreous loss in the study eye;
16. Congenital eye malformations in the study eye;
17. A history of penetrating ocular trauma in the study eye;
18. Patient under administrative or legal supervision;
19. Females of childbearing potential (i.e., who are not postmenopausal for at least 1 year or surgically sterile for at least 6 weeks prior to Visit 1 - Screening/Randomization) who are lactating, or who are pregnant as determined by a positive urine pregnancy test (UPT) at Visit 1 - Screening/Randomization.
20. Participation in any other investigational device or drug clinical research study within 30 days of Visit 1 - Screening/Randomization.

E.5 End points

E.5.1

Primary end point(s)

• Change from baseline in OCT at Day 84 (=3 months) with subfoveal central macular thickness (CMT) measured in microns using SD-OCT.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1 and Day 84

E.5.2

Secondary end point(s)

Secondary endpoints :
1. Efficacy:
1.1. To evaluate subfoveal central macular thickness (CMT) measured in microns using SD-OCT at D1, D14, D28, and D56;
1.2. To evaluate the best corrected visual acuity (BCVA) assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) scale from Day 1 to Days 14, 28, 56, 84;
1.3. To evaluate changes of area of CNV component lesion with fluorescein and indocyanine green angiography at D1, D28 and D56 (evidence of late leakage or pooling of the dye).

2. Safety assessment:
2.1. Slit-lamp Examination: areas to be assessed include conjunctiva, cornea, anterior chamber, and lens; determination of normal or abnormal status made by Investigators; change from D1 to D14, D28, D56 and D84;
2.2. Ocular Fundus Finding: areas to be assessed include vitreous, fundus, optic nerve, macula and choroid, vessels and peripheral retina; determination of normal or abnormal status made by Investigators; change from D1 to D14, D28, D56 and D84;
2.3. Intraocular Pressure: measured in millimeters of mercury (mmHg) by air tonometry; change from D1 to D14, D28, D56 and D84;
2.4. Ocular Adverse event change: ocular and non-ocular events collected and summarized descriptively; change from D1 to D14, D28, D56 and D84.

E.5.2.1

Timepoint(s) of evaluation of this end point

For efficacity endpoints, the evaluation will take place at D1, D14, D28, D56 and D84
For safety endpoints, the evaluation will take place at D1, D14, D28, D56 and D84

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

last visit of the last subject

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

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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)

Treatment with reference treatment for AMD

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

2019-04-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-19

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-04-19

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