Clinical Trials Register

Summary
EudraCT Number:	2019-004838-41
Sponsor's Protocol Code Number:	CSOK583A12301
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-10-29
Trial results	View 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

2019-004838-41

A.3

Full title of the trial

A 52-week multicenter, randomized, double-masked, 2-arm parallel study to compare efficacy, safety and immunogenicity of SOK583A1 to Eylea®, administered intravitreally, in patients with neovascular age-related macular degeneration

A.3.1

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

The study is investigating the use of an investigational medication (SOK583A1, a proposed biosimilar medicine to Eylea®) in wet AMD patients. The aim of study is to demonstrate similar safety and efficacy of the proposed biosimilar to the originator

A.3.2

Name or abbreviated title of the trial where available

MYLIGHT

A.4.1

Sponsor's protocol code number

CSOK583A12301

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	Hexal AG
B.1.3.4	Country	Germany
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	Hexal AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hexal AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Industriestr. 25
B.5.3.2	Town/ city	Holzkirchen
B.5.3.3	Post code	83607
B.5.3.4	Country	Germany
B.5.6	E-mail	biosimilar.clinicaltrials@sandoz.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	Aflibercept
D.3.2	Product code	SOK583A1
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	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AFLIBERCEPT
D.3.9.1	CAS number	862111-32-8
D.3.9.2	Current sponsor code	SOK583A1
D.3.9.3	Other descriptive name	AFLIBERCEPT
D.3.9.4	EV Substance Code	SUB26987
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	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	European Union
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	Eylea
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	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AFLIBERCEPT
D.3.9.1	CAS number	862111-32-8
D.3.9.3	Other descriptive name	AFLIBERCEPT
D.3.9.4	EV Substance Code	SUB26987
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	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

The ‘wet’ form of age-related macular degeneration (AMD) is a disease which affects the central part of the retina (called the macula) at the back of the eye. The wet form of AMD is caused by choroidal neovascularisation (the abnormal growth of blood vessels under the macula), which may leak fluid and blood and cause swelling (Eylea SmPC)

E.1.1.1

Medical condition in easily understood language

The wet form of AMD is caused by the abnormal growth of blood vessels under the macula (central part of the retina), which may leak fluid and blood and cause swelling.

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	10075568
E.1.2	Term	Wet age-related macular degeneration
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 demonstrate similar efficacy of SOK583A1 and Eylea EU in terms of BCVA

E.2.2

Secondary objectives of the trial

- To evaluate if the anatomical outcome of SOK583A1 is similar to Eylea EU
- To evaluate if the efficacy of SOK583A1 is similar to Eylea EU in terms of BCVA
- To evaluate if SOK583A1 is similar to Eylea EU in terms of safety
- To evaluate if SOK583A1 is similar to Eylea EU in terms of immunogenicity
- To evaluate the systemic exposure of SOK583A1 and Eylea EU in participants of the PK assessment

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A descriptive PK substudy in 40 patients to confirm that the low systemic exposure of SOK583A1 is within the same range observed following Eylea EU after IVT administration.

E.3

Principal inclusion criteria

Participants eligible for inclusion in this study must meet all of the following criteria:
1. Signed informed consent must be obtained prior to participation in the study
2. Participants must be 50 years of age or older at Screening
3. Anti-VEGF treatment-naive patients for either eye and systemically
4. Study eye diagnosed with active CNV lesions (type 1 and/or type 2) secondary to AMD and/or Retinal Angiomatous Proliferation lesions (type 3), affecting the central subfield. Active CNV lesion is defined by the presence of leakage as evidenced by fluorescein angiography, and intra- or subretinal fluid as evidenced by optical coherence tomography, both confirmed by the CRC at Screening
5. Total area of CNV (including both classic and occult components) must comprise > 50% of the total lesion area in the study eye, confirmed by the CRC at Screening
6. BCVA between 73 and 38 letters, both inclusive, in the study eye at Screening and Baseline using ETDRS testing charts
7. Willing and able to comply with all study procedures, and be likely to complete the study
8. Clear ocular media and adequate pupil dilatation in both eyes to permit good quality photographic imaging

E.4

Principal exclusion criteria

Participants meeting any of the following criteria are not eligible for inclusion in this study.
Ocular conditions and treatments:
1.Previous treatment with any anti-VEGF therapy in either eye or investigational drugs in study eye or fellow eye, at any time prior to Baseline
2.Participant has received any approved treatment for nAMD (other than vitamin and dietary supplements) in the study eye and at any time prior the Baseline
3.Presence of other causes of CNV, including diabetic retinopathy, pathologic myopia (spherical equivalent of –8 diopters or more negative, or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye
4.Any active or suspected intraocular or periocular infection or active or suspected intraocular inflammation (e.g infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in either eye at Screening or Baseline
5.Subfoveal fibrosis, atrophy, or scarring extending > 50% of total lesion area in the study eye as assessed by the Investigator at Screening and confirmed by the CRC prior to randomization
6.Subretinal hemorrhage that is ≥ 50% of the total lesion area in the study eye, or if the subretinal hemorrhage involving the fovea is 1 or more disc areas (≥ 2.54 mm2 ) in size in the study eye, as assessed by FA and confirmed by the CRC
7.RPE rip/tear in the study eye at Screening or Baseline
8.Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Baseline
9.History or evidence of the following, in the study eye:
•Intraocular (including cataract surgery) or refractive surgery within the 90 day period prior to Baseline. The YAG posterior capsulotomy is allowed no later than 4 weeks prior to Baseline
•Previous penetrating keratoplasty or vitrectomy
•Previous panretinal photocoagulation or photodynamic therapy
•Previous submacular surgery or other surgical intervention for AMD
•Retinal detachment or treatment or surgery for retinal detachment
•Any history of macular hole of stage 2 and above
•Prior trabeculectomy or other filtration surgery
•Ocular trauma within 6-months prior to Baseline
10.History of hypersensitivity to any of the study treatments or its excipients, or clinically relevant sensitivity to fluorescein dye, as assessed by the Investigators
11.Uncontrolled glaucoma in the study eye defined as IOP > 25 mmHg on medication or according to Investigator’s judgment at Screening or Baseline
12.Aphakia and/or absence of the posterior capsule in the study eye at Screening or Baseline, unless it occurred as a result of a YAG posterior capsulotomy in association with prior posterior chamber intraocular lens implantation
13.Intra or periocular use of corticosteroids in the study eye within a 6 month period prior to Baseline
14.Use of topical ocular corticosteroids in the study eye for 30 or more consecutive days within the 90 days period prior to Baseline
15.Previous therapeutic radiation near the region of the study eye
16.Concomitant conditions or ocular disorders in the study eye, including media opacities, cataract and diabetic macular edema, at Screening or Baseline which could, in the opinion of the Investigator, prevent response to study treatment or may confound interpretation of study results (efficacy and safety), compromise visual acuity or require medical or surgical intervention during the course of the study
17.Presence of amblyopia, amaurosis or ocular disorders with BCVA <38 letters (ETDRS testing charts) in the fellow eye at Screening (except when due to conditions whose surgery may improve VA, e.g. cataract)
18.Presence of Scleromalacia in either eye
19.Participants requiring anti-VEGF treatment of the fellow eye at Baseline will not be eligible for the PK substudy
Systemic conditions and treatments:
20.Previous systemic treatment with any anti-VEGF therapy
21.Use of systemic corticosteroids for 30 or more consecutive days within the 90 days prior to Baseline, with the exception of low stable doses of corticosteroids (defined as ≤ 10 mg prednisolone or equivalent dose used for 90 days or more).
22.Uncontrolled blood pressure defined as a systolic value ≥ 160 mmHg or diastolic value ≥ 100 mmHg at Screening
23.Stroke or myocardial infarction during the 6-month period prior to Baseline
24.Pregnant or nursing (lactating) women and women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 3 months after stopping the medication.

Other protocol-defined exclusion criteria may apply (please see protocol section 5.2 for full exclusion list)

E.5 End points

E.5.1

Primary end point(s)

Mean change from baseline in BCVA score using ETDRS testing charts

E.5.1.1

Timepoint(s) of evaluation of this end point

Mean change from baseline in BCVA score using ETDRS testing charts at Week 8

E.5.2

Secondary end point(s)

• Mean change in CSFT using SD-OCT from Baseline
• Mean change of CNV lesion size using FA from Baseline
• Mean change from Baseline in BCVA score using EDTRS testing charts
• Incidence of ocular and non-ocular AEs
• Development of binding and neutralizing ADAs
• Aflibercept concentration assessments

E.5.2.1

Timepoint(s) of evaluation of this end point

• Mean change in CSFT using SD-OCT from Baseline to Week 1, 4, 8, 24 and 52
• Mean change of CNV lesion size using FA from Baseline to Week 8 and 52
• Mean change from Baseline in BCVA score using EDTRS testing charts at Week 24 and 52
• Incidence of ocular and non-ocular AEs over 52 weeks
• Development of binding and neutralizing ADAs up to Week 52
• Aflibercept concentration assessments at Baseline (pre-dose) and 24 hours after the first and third injections

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

Yes

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

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

Yes

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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)

Yes

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Israel

Japan

New Zealand

Russian Federation

Ukraine

United States

Austria

Bulgaria

France

Germany

Hungary

Latvia

Lithuania

Poland

Portugal

Romania

Slovakia

Spain

Czechia

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

Study completion is defined as the date when the last patient finishes
the End of Study Visit/Early Termination Visit, or the date at which the
last data point from the last patient is received, whichever is later.

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

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:

414

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

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

253

F.4.2.2

In the whole clinical trial

460

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)

The Investigator is advised to provide appropriate follow-up nAMD treatment for all participants completing the study or prematurely withdrawn from the study.

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

2021-04-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-05-10

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