ICH GCP - EU Clinical trials Registry - 2018-002611-99 (NL)

Clinical Trials Nct Page

Summary
EudraCT Number:	2018-002611-99
Sponsor's Protocol Code Number:	20090
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-05-07
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

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2018-002611-99

A.3

Full title of the trial

Open-label, randomized, two–arm, controlled study to assess the efficacy, safety, and tolerability of intravitreal (IVT) aflibercept compared to laser photocoagulation in patients with retinopathy of prematurity (ROP)

A.3.1

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

Aflibercept for retinopathy of prematurity – intravitreal injection versus laser therapy

A.3.2

Name or abbreviated title of the trial where available

FIREFLeYe

A.4.1

Sponsor's protocol code number

20090

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/115/2019

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bayer 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	Bayer 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	Bayer AG
B.5.2	Functional name of contact point	Bayer Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	CTP Team/Ref: 'EU CTR' /Bayer AG
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.4	Telephone number	4930300139003
B.5.6	E-mail	clinical-trials-contact@bayer.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	Yes
D.2.1.1.1	Trade name	Eylea 40mg/ml solution for injection in a vial
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	Aflibercept
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	BAY 86-5321
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	Yes
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

Retinopathy of prematurity

E.1.1.1

Medical condition in easily understood language

Retinopathy of prematurity

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	20.1
E.1.2	Level	PT
E.1.2	Classification code	10038933
E.1.2	Term	Retinopathy of prematurity
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of aflibercept in subjects diagnosed with retinopathy of prematurity (ROP) in comparison to laser

E.2.2

Secondary objectives of the trial

To assess the safety and tolerability of aflibercept
To assess the treatment burden of aflibercept and laser
To describe the systemic exposure to aflibercept

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Gestational age at birth ≤ 32 weeks or birth weight ≤ 1500 g
Type of Participant and Disease Characteristics
2.Subjects with treatment-naïve ROP classified according to the International Classification for ROP in at least one eye as:
- Zone I Stage 1 plus, or 2 plus, or 3 non-plus or 3 plus, or Zone II Stage 2 plus or 3 plus, or AP-ROP
3.Weight at baseline (day of treatment) ≥ 800 g
4.Male or female
5.Signed informed consent from parent(s)/legally authorized representative(s) as described in Section 10.1.3 of the clinical trial protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the clinical trial protocol

E.4

Principal exclusion criteria

Subjects are excluded from the study if any of the following “per subject” criteria are met. A potential study eye is excluded from the study if any of the “per eye” criteria are met:
Medical Conditions – per subject
1.Known or suspected chromosomal abnormality, genetic disorder or syndrome
2.Previous exposure to any IVT or systemic anti-VEGF agent, including maternal exposure during pregnancy and/or during breastfeeding
3.Clinically significant neurological disease (eg, intraventricular hemorrhage grade 3 or higher, periventricular leukomalacia, congenital brain lesions significantly impairing optic nerve function, severe hydrocephalus with significantly increased intracranial pressure)
4.Pediatric conditions rendering the infant ineligible for study intervention at baseline or for repeated blood draws as evaluated by a NICU specialist and a study ophthalmologist
5.Presence of active ocular infection within 5 days of the first treatment
Medical Conditions – per eye
6.Advanced stages of ROP with partial or complete retinal detachment (ROP Stages 4 and 5)
7.ROP involving only Zone III
8.Ocular abnormalities that may interfere with the administration of study intervention or assessment of the study primary endpoint Prior/Concomitant Therapy – per subject
9.Postnatal treatment with oral or intravenous corticosteroids at an equivalent dose of prednisone ≥ 1 mg/kg/day for > 2 weeks within 14 days of the first study intervention
Prior/Concomitant Therapy – per eye
10.Previous surgical or nonsurgical treatment for ROP (IVT anti-VEGF injection, ablative laser therapy, cryotherapy, and vitrectomy) Prior/Concurrent Clinical Study Experience
11.Participation of the subject or the mother in other clinical trials requiring administration of investigational treatments (other than vitamins and minerals) at the time of screening, or within 30 days or 5 half-lives of administration of the previous study drug, whichever is longer

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint
Proportion of patients with absence of active ROP and unfavorable structural outcomes at 24 weeks after starting study treatment

E.5.1.1

Timepoint(s) of evaluation of this end point

at 24 weeks after starting study Treatment

E.5.2

Secondary end point(s)

Secondary Endpoints addressing primary objectives
Requirement for intervention with a second treatment modality from baseline to Week 24
Recurrence of ROP from baseline to Week 24
To explore new Retinopathy of Prematurity Activity Scale proposed by the International Neonatal Consortium

Secondary Endpoints addressing secondary objectives
•Number of aflibercept administrations from baseline to Week 24
•Number of laser treatments from baseline to Week 24
•Proportion of participants with ocular TEAEs and SAEs from baseline to Week 24
•Proportion of participants with systemic TEAEs and SAEs from baseline to Week 24
•Systemic exposure to free aflibercept (at expected maximum plasma concentration and during elimination period from plasma) determined by sparse sampling
•Presence of anti-drug antibodies before and 12 weeks after aflibercept injection

E.5.2.1

Timepoint(s) of evaluation of this end point

• From baseline to Week 24

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

Yes

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)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Laser Therapy

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

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

Argentina

Austria

Belgium

Brazil

Bulgaria

Canada

Czechia

Estonia

France

Germany

Greece

Hong Kong

Hungary

Israel

Italy

Japan

Korea, Democratic People's Republic of

Latvia

Lithuania

Malaysia

Netherlands

Poland

Portugal

Romania

Russian Federation

Singapore

Slovakia

Spain

Sweden

Switzerland

Taiwan

Turkey

Ukraine

United Kingdom

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

The end of the study as a whole is defined as the date of the last visit of the last subject in the study in all centers in all participating countries (EU and non-EU).

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 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

Yes

F.1.1

Number of subjects for this age range:

135

F.1.1.1

In Utero

F.1.1.2

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

Yes

F.1.1.2.1

Number of subjects for this age range:

135

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)

F.1.3

Elderly (>=65 years)

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Preterm newborn infants will be involved

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

135

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)

A Phase 3b study (Study 20275; extension study) is planned to assess the long-term outcomes of subjects who received study intervention in this study and accept participation in the extension 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

2019-05-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-07-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-02-12

Clinical Trials Nct Page

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner