Clinical Trials Register

Summary
EudraCT Number:	2010-024290-40
Sponsor's Protocol Code Number:	CAH/Ulc/2010
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-03-09
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

Spain - AEMPS

A.2

EudraCT number

2010-024290-40

A.3

Full title of the trial

Multicenter clinical trial to evaluate the safety and feasibility of allogeneic tissue engineered product (human nanostructured artificial cornea) in patients with advanced corneal trophic ulcers refractory to (ophtalmic) conventional treatment.

Ensayo clínico multicéntrico para la evaluación de la seguridad y factibilidad de un medicamento de ingeniería tisular alogénico (córnea artificial humana nanoestructurada) en pacientes con úlceras corneales de tipo trófico en estadios avanzados refractarias a tratamiento (oftalmológico) convencional

A.3.1

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

Study of an artificial human tissue medicament for patients with severe corneal ulcers that not respond to conventional therapies.

Estudio de un medicamento (córnea artificial humana) en pacientes con úlceras corneales que no responden a tratamiento oftalmológico convencional.

A.4.1

Sponsor's protocol code number

CAH/Ulc/2010

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	FUNDACIÓN PROGRESO Y SALUD
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	MINISTERIO DE SANIDAD, POLITICA SOCIAL E IGUALDAD
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	INICIATIVA ANDALUZA EN TERAPIAS AVANZADAS
B.5.2	Functional name of contact point	ANA CARDESA GIL
B.5.3	Address:
B.5.3.1	Street Address	MAESE RODRIGO, Nº 1, 1ª planta izquierda
B.5.3.2	Town/ city	SEVILLA
B.5.3.3	Post code	41001
B.5.3.4	Country	Spain
B.5.4	Telephone number	34955 01 90 40
B.5.5	Fax number	34955 01 90 19
B.5.6	E-mail	terapias.avanzadas@juntadeandalucia.es

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	human nanostructured artificial cornea
D.3.4	Pharmaceutical form	Ophthalmic insert
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ophthalmic use (Noncurrent) Intraocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	expanded human cells in culture from small biopsies of human scleral-corneal limbus from cadaver donors and natural biomaterials and biocompatible nan
D.3.9.3	Other descriptive name	expanded human cells in culture from small biopsies of human scleral-corneal limbus from cadaver donors and natural biomaterials and biocompatible nanostructured fibrin and agarose.
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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)	Yes
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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

trophic corneal ulcers refractaries to conventional treatment

Úlceras corneales de tipo trófico en estadios avanzados refractarias a tratamiento (oftalmolgógico) convencional

E.1.1.1

Medical condition in easily understood language

corneal ulcers refractaries to conventional treatment

Úlceras corneales avanzadas que no responden a tratamiento (oftalmolgógico) convencional

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10048492
E.1.2	Term	Corneal ulcer
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

To evaluate the safety, feasibility and evidence of clinical efficacy of a model of human artificial nanostructured lamellar corneal, in patients with severe corneal disease for which there is currently no effective therapeutic.

Evaluar la seguridad, factibilidad e indicios de eficacia clínica de un modelo de córnea artificial humana nanoestructurada lamelar anterior, en un grupo de pacientes afectos de patología corneal grave, para los cuales no existe actualmente una alternativa terapéutica eficaz.

E.2.2

Secondary objectives of the trial

1.Generate artificial corneas nanostructured lamellar human allogeneic, from cadaver donor origin from sclero-corneal limbus and biomaterials
2.Implement the nanostructured artificial corneas human in a group of patients randomized to the experimental group, suffering from severe corneal disease. 3 .To evaluate the biosafety of nanostructured artificial corneas human implanted in patients to rule out adverse reactions of relevance.

1.- Generar córneas artificiales humanas nanoestructuradas lamelares de origen alogénico de donante cadáver a partir de limbo esclero-corneal y biomateriales de fibrina y agarosa.
2.- Implantar las córneas artificiales humanas nanoestructuradas de origen alogénico de donante cadáver en un grupo de pacientes, aleatorizados a grupo experimental, afectos de patología corneal grave a modo de injerto en el lecho de la lesión.
3.- Evaluar la bioseguridad de las córneas artificiales humanas nanoestructuradas de origen alogénico de donante cadáver implantadas en los pacientes para descartar reacciones adversas de relevancia.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Patients give their informed consent for study participation.
2.Corneal ulcers stage 3 Mackie that do not respond to conventional medical treatment.
3.There must be involvement stromal, but with a depth not reach Descemet's membrane.
4.No active ocular infection
5.Duration of the disease causing corneal ulcer less than 6 weeks

1.Pacientes que otorguen su consentimiento informado para la participación en el estudio.
2.Presencia de úlceras corneales en estadio 3 de Mackie que no respondan al tratamiento médico convencional.
3.Debe existir afectación estromal, pero con una profundidad que no alcance la membrana de Descemet. La localización puede ser central y/o periférica.
4.Ausencia de infección ocular activa.
5.Pacientes de ambos sexos mayores de 18 años, no existiendo límite de edad superior.
6.Duración de la enfermedad causante de la úlcera corneal igual o superior a 6 semanas.
7.Pacientes con parámetros analíticos normales, definidos por:
-Leucocitos > 3000
-Neutrófilos > 1500
-Plaquetas > 100000
-AST/ALT < 1.5 rango estándar institución
-Creatinina < 1.5 mg/dl

E.4

Principal exclusion criteria

1.Absence of stromal involvement.
2.Corneal disease that responds well to standard medical treatments in a shorter period of 3 to 5 weeks.
3. Active ocular infection
4.Positive serology for HBV, HCV, HIV or coexistence of other pathology, at the discretion of the investigator, prevent patient monitoring in the trial.
5. Pregnancy or risk or pregnancy
6. History of previous diagnosis of neoplasia, except orbital neoplasia.

1.Ausencia de afectación estromal (por ejemplo, defectos epiteliales persistentes).
2.Patología corneal que responda correctamente a tratamientos médicos habituales en un plazo menor de 3 ? 5 semanas.
3.Infección ocular activa.
4.Serología positiva para VHB, VHC, HIV o coexistencia de cualquier otra patología que, a criterio del investigador, impida el seguimiento del paciente en el ensayo.
5.Mujeres gestantes o en periodo de lactancia o mujeres en edad fértil que no utilicen un método anticonceptivo de eficacia probada. Se describe como método anticonceptivo altamente efectivo aquel método anticonceptivo oral (que combine estrógenos con gestágenos) o de otro tipo como, por ejemplo, un anticonceptivo hormonal inyectable, implantable o en parche, DIU o esterilización quirúrgica, (siempre que los anticonceptivos hormonales no interaccionen con el medicamento en investigación).
6.Antecedentes de neoplasia, excepto neoplasia orbital.
7.Pacientes que hayan participado en los últimos 3 meses previos a la inclusión del estudio en un ensayo clínico.

E.5 End points

E.5.1

Primary end point(s)

To evaluate the safety, feasibility and evidence of clinical efficacy of a model of human artificial nanostructured lamellar corneal.

oAparición de acontecimientos adversos y acontecimientos adversos graves.
oEstado del constructo corneal implantado: mantenimiento de su integridad, desprendimiento o reabsorción.
oSignos de infección local, regional o general.
oVascularización inducida: gradación por cuadrantes y profundidad.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 month

24 meses

E.5.2

Secondary end point(s)

1.- To generate human artificial nanostructured corneas of autologous origin from tissue biopsies of the corneal limbus of a group of patients and fibrin-agarose biomaterials.
2.- To implant the autologous human artificial nanostructured corneas in a group of patients with severe corneal disease by partial anterior lamellar keratoplasty.
3.- To evaluate the level of biosafety of the implanted autologous human artificial nanostructured corneas to detect any significant adverse effect.

E.5.2.1

Timepoint(s) of evaluation of this end point

24 month

24 meses

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

First administration to humans

1ª administración en humanos

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

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

Yes

E.8.2.3.1

Comparator description

Trasplante de menbrana amniótica

usual treatment of their condition, consisting of amniotic membrane transplantation

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

The trial ends when the last patient enrolled has had 24 months of follow-up

El ensayo finalizará a los 24 meses de seguimiento del último paciente incluido.

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

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.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)

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

2012-12-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-10-13

P. End of Trial
P.	End of Trial Status	Ongoing

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