Clinical Trials Register

Summary
EudraCT Number:	2014-000300-10
Sponsor's Protocol Code Number:	IDI-AFLI-2013-01
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-04-04
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

Spain - AEMPS

A.2

EudraCT number

2014-000300-10

A.3

Full title of the trial

Phase IV study to evaluate the efficacy of aflibercept in naive patients with retinal angiomatous proliferation (RAP) lesions on an individualized ?Treat and Extend? (TAE) regimen. AFLIRAP Study.

Ensayo clínico en fase IV para evaluar la eficacia de aflibercept en pacientes naive con lesiones de proliferación angiomatosa de la retina (RAP) en régimen de tratamiento individualizado Treat and Extend (TAE). Estudio AFLIRAP

A.3.1

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

Study, to evaluate the effectiveness of aflibercept in patients with RAP (retinal angiomatous proliferation) lesions.

Estudio para evaluar la eficacia de aflibercept en pacientes con lesiones RAP (proliferación angiomatosa de la retina)

A.3.2

Name or abbreviated title of the trial where available

AFLIRAP

A.4.1

Sponsor's protocol code number

IDI-AFLI-2013-01

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	Fundació Instituto de Investigación Biomédica de Bellvitge (Fundació IDIBELL)
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bayer
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Trial Form Support
B.5.2	Functional name of contact point	Elisabet Molina
B.5.3	Address:
B.5.3.1	Street Address	C/ Consell de Cent, 334 - 4ª planta
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08009
B.5.3.4	Country	Spain
B.5.4	Telephone number	34931850200
B.5.5	Fax number	34931850257
B.5.6	E-mail	elisabet.molina@tfscro.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
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Pharma AG
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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.3.2	Product code	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.3.9.3	Other descriptive name	AFLIBERCEPT
D.3.9.4	EV Substance Code	SUB26987
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	Yes
D.3.11.13.1	Other medicinal product type	Aflibercept (VEG-Trap-Eye) is a fusion protein with high VEGF affinity attributed to binding sequences from the native receptors VEGFR1 ans VEGFR2

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

Retinal angiomatous proliferation lesions (RAP)

Lesiones de proliferación angiomatosa de la retina (RAP)

E.1.1.1

Medical condition in easily understood language

Retinal angiomatous proliferation lesions (RAP)

Lesiones de proliferación angiomatosa de la retina (RAP)

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Mean BCVA (best-corrected visual acuity) change (ETDRS letters) at 12-months (52 weeks).

Este estudio está diseñado para evaluar la eficacia del tratamiento con aflibercept en pacientes naive con lesiones de proliferación angiomatosa de la retina (RAP)

E.2.2

Secondary objectives of the trial

? Proportion of patients gaining 15 or more letters at 12-months
? Mean BCVA (best-corrected visual acuity) change (ETDRS letters) at 12 weeks.
? Mean foveal thickness change on SD-OCT (spectral domain optical coherence tomography) scans at 12 weeks & 52 weeks.
? Proportion of patients with no intraretinal/subretinal fluid on SD-OCT scans at 12 weeks & 52 weeks.
? Mean PED height change on SD-OCT scans at at 12 weeks & 52 weeks.
? Mean number of intravitreal injections.
? Percentage of patients only requiring mandatory doses
? Mean change of hypofluorescent areas on FAF (fundus autofluorescence) at 12-months.

? Porcentaje de pacientes con ganancia ? de 15 letras a los 12 meses.
? Evaluar el cambio medio en la MAVC después de la dosis de carga a las 12 semanas.
? Cambio medio en el grosor foveal mediante la SD-OCT (tomografía de coherencia óptica de dominio espectral) a la semana 12 y semana 52.
? Cambio medio del grosor coroideo mediante la SD-OCT (tomografía de coherencia óptica de dominio espectral) a la semana 12 y semana 52.
? Porcentaje de pacientes libres de fluido intra o subretiniano en la SD-OCT a la semana 12 y semana 52.
? Cambio medio de la altura del desprendimiento del epitelio pigmentario retiniano (EPR) en la SD-OCT a la semana 12 y semana 52.
? Describir el número medio de inyecciones al final del estudio y su distribución a lo largo del mismo.
? Porcentaje de pacientes que no requieren inyecciones adicionales (solo obligatorias).
? Cambio medio de áreas hipofluorescentes sobre AF (Autofluorescencia) a los 12 meses.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

? Signed Informed Consent
? Men and women ? 50 years of age.
? RAP lesions (stages I and II) with no previous treatment.
? ETDRS best-corrected visual acuity of: 20/32 to 20/320 (letter score of 73 to 25) in the study eye.
? BCVA >20/400 in the fellow eye.
? Absence of significant cataract that could affect visual results.
? Able to return for ALL clinic visits and complete all study-related procedures.
? Absence of other ocular diseases that could affect visual acuity.

? Hombres o mujeres con edad igual o superior a 50 años.
? Paciente con lesiones RAP (estadios I y II) y no tratados previamente.
? Pacientes con una puntuación de MAVC basal entre 78 y 23 letras, ambas inclusive, medido mediante el optotipo ETDRS a 4 metros (equivalente al optotipo Snellen de 20/25 y 20/320) en el ojo de estudio.
? Pacientes con una puntuación de MAVC basal medida con ETDRS a 4 metros de distancia mayor o igual a 20/400 en el optotipo de Snellen (0,05 decimal, 1 línea de visión) en el ojo contralateral.
? Pacientes con ausencia de cataratas (opacidades) de intensidad suficiente que pudiera afectar a los resultados visuales.
? Pacientes que estén dispuestos, comprometidos y sean capaces de asistir a todas las consultas y realizar todos los procedimientos relacionados con el estudio.
? Pacientes que no presenten otras enfermedades oculares que puedan afectar la agudeza visual.
? Pacientes que otorguen su consentimiento firmado antes de proceder a cualquier evaluación y consientan expresamente la inclusión de los datos de su historia clínica así como los resultantes de la participación en el estudio en un fichero de datos personales bajo la responsabilidad del Centro.

E.4

Principal exclusion criteria

? Previous anti-VEGF therapy, photodynamic therapy or thermal laser in the study eye.
? Recent cataract surgery (<3 months) in the study eye.
? Any concurrent ocular disease that could affect the final outcome (diabetic retinopathy, advanced glaucoma, pathologic myopia).
? No scar, fibrosis, or atrophy involving the center of the fovea
? No RPE rip/tear involving the central fovea
? Participation in any other interventional clinical trial trial
? History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in the study eye
? Active intraocular inflammation in the study eye
? History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment.
? Unable to undergo fluorescein angiography or fundus photography because of uncontrolled allergies

? Pacientes en tratamiento previo con terapia anti-VEGF, terapia fotodinámica (TFD) o láser térmico en el ojo de estudio.
? Pacientes con cirugía intraocular (incluyendo cirugía de cataratas) en el ojo de estudio en los 3 meses previos a la visita basal.
? Pacientes con cualquier otra/s enfermedad/des ocular/es que pueda conducir a la disminución de la agudeza visual (retinopatía diabética, glaucoma avanzado, miopía patológica).
? Pacientes con cicatriz, fibrosis o atrofia que afecte el centro de la fóvea en el ojo de estudio.
? Pacientes con desgarros/roturas en el epitelio pigmentario de la retina (EPR) que afecten el centro de la fóvea en el ojo de estudio.
? Pacientes con antecedentes de cirugía de vitrectomía, cirugía submacular, u otras cirugías de intervención para la degeneración macular relacionada con la edad (DMAE) en el ojo de estudio.
? Pacientes con inflamación intraocular activa en el ojo de estudio.
? Pacientes con antecedentes de accidente cerebrovascular, infarto de miocardio o ataques isquémicos transitorios en los 3 meses previos al inicio del estudio.
? Pacientes que no pueden someterse a una angiografía fluoresceínica o fotografía de fondo del ojo debido a alergias no controladas.
? Mujeres potencialmente fértiles que tengan previsto quedarse embarazadas, estén embarazadas y/o en periodo de lactancia, o bien que no deseen utilizar un método anticonceptivo eficaz (anticonceptivos hormonales [implantación, parches, oral], y métodos de doble barrera [cualquier combinación doble de: DIU, profilácticos masculinos o femeninos con gel espermicida, diafragma, esponja anticonceptiva, capuchón cervical]).
? Pacientes con incapacidad de cumplir con el estudio y los procedimientos de seguimiento.
? Pacientes que estén participando de forma simultánea en otro(s) ensayo(s) clínico(s).

E.5 End points

E.5.1

Primary end point(s)

Mean BCVA (best-corrected visual acuity) change (ETDRS letters) at 12-months (52 weeks).

Evaluar el cambio medio en la Mejor Agudeza Visual Corregida (MAVC) medida en letras mediante el optotipo ETDRS entre las visitas basal y final (12 meses)

E.5.1.1

Timepoint(s) of evaluation of this end point

In week 52

En semana 52

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

Specified above

Especificado arriba

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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.8.3

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

Last patient last visit

La última visita del ultimo paciente

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.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)

NA for this trial

No aplica para este estudio

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

2014-04-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-04-07

P. End of Trial
P.	End of Trial Status	Completed

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