Clinical Trials Register

Summary
EudraCT Number:	2011-003551-18
Sponsor's Protocol Code Number:	AMASCIS-01/2011
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:	2011-12-07
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

2011-003551-18

A.3

Full title of the trial

Reparative Therapy In Acute Ischemic Stroke With Alogeneic Mesenchymal Stem Cells From Adipose Tissue. Safety Assessment. A Randomised, Double Blind Placebo? Controlled Single Center Pilot Clinical Trial

TERAPIA REPARADORA EN EL INFARTO CEREBRAL AGUDO CON CÉLULAS TRONCALES MESENQUIMALES ALOGÉNICAS DE TEJIDO ADIPOSO. ANÁLISIS DE SEGURIDAD. ENSAYO CLÍNICO PILOTO UNICÉNTRICO, ALEATORIZADO, DOBLE CIEGO, CONTROLADO CON PLACEBO.

A.3.1

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

Single Center Pilot Clinical Trial on cell therapy in acute ictus

Ensayo clínico piloto unicéntrico de terapia celular en ictus agudo

A.4.1

Sponsor's protocol code number

AMASCIS-01/2011

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	FIBHULP
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, Política 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	UCICEC LA PAZ
B.5.2	Functional name of contact point	UCICEC
B.5.3	Address:
B.5.3.1	Street Address	Paseo de la Castellena, 261
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28046
B.5.3.4	Country	Spain
B.5.4	Telephone number	34917277558
B.5.5	Fax number	34912071876
B.5.6	E-mail	maria.yllescas@idipaz.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	Allogeneic eASCs
D.3.2	Product code	Cx611
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Allogeneic eASCs
D.3.9.2	Current sponsor code	Cx611
D.3.9.3	Other descriptive name	Allogeneic eASCs
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000000
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	Yes
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	Suspension for injection
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

acute ischemic stroke

ictus isquémico agudo

E.1.1.1

Medical condition in easily understood language

CEREBRAL INFARCTION

Infarto cerebral

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10061256
E.1.2	Term	Ischaemic stroke
E.1.2	System Organ Class	10029205 - Nervous system 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 of treatment with allogeneic stem cells from human adipose tissue in patients with acute ischemic stroke

Evaluar la seguridad del tratamiento con células troncales alogénicas procedentes de tejido adiposo humano en pacientes con ictus isquémico agudo.

E.2.2

Secondary objectives of the trial

1.-To analyze the potential effectiveness of treatment with allogeneic stem cells from human adipose tissue in patients with acute ischemic stroke using the following parameters:
a) Recuperación a los 3 meses mediante la evaluación de las diferencias en la escala de Rankin modificada (mRS) y en la escala de ictus NIH

b) total volume of stroke by performing MRI.

2.- To identify changes in biochemical markers of brain repair as VEGF, BDNF, MMP-9 and its relationship to neurological and functional outcomes.

1. Analizar la eficacia potencial del tratamiento con células troncales alogénicas procedentes de tejido adiposo humano en pacientes con ictus isquémico agudo mediante los siguientes parámetros:
a) Recuperación a los 3 meses mediante la evaluación de las diferencias en la escala de Rankin modificada (mRS) y en la escala de ictus NIH
b)Volumen total del infarto medido en RM.

2. Identificar cambios en los marcadores bioquímicos de reparación cerebral como VEGF, BDNF, MMP-9 y su relación con los resultados neurológicos y funcionales.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female acute ischemic patients aged 60-80 years
2. Patients should be treated within 2 weeks from stroke onset. If the time of onset is unknown, use the time when the patient was last known to be well.
3. Patients with a measurable focal neurological deficit for at least 60 minutes. This deficit must persist from the beginning to the time of treatment without clinically meaningful improvement.
4. Patients must have computerized tomography (CT) and / or magnetic resonance imaging (MRI) compatible with the clinical diagnosis of acute ischemic stroke in the territory of the middle cerebral artery before being included in the study.
5. Patients must have a score on the NIH Stroke Scale 8-20, with at least 2 of these points in Sections 5 and 6 (motor deficit) at the time of inclusion.
6. Immediately (i.e. few minutes) before the stroke, patients should have a score on the mRS ? 1 (no symptoms at all or no significant disability despite symptoms, able to perform everyday tasks and activities).
7. Women of childbearing age should have a negative pregnancy test performed prior to inclusion.
8. Obtaining informed consent signed (after a detailed explanation of the nature and purpose of this study, the patient or guardian or legal representative must give their consent to participate by signing the informed consent document). Assent from a relative or career if the patient is unable to give meaningful consent (e.g. in cases of dysphasia, confusion, or reduced conscious level).

1. Hombre o mujer de 60-80 años con síntomas de infarto cerebral agudo de menos de 12h horas de evolución. Si el momento de inicio de los síntomas es desconocido, se tomará como referencia el último momento en que el paciente fue visto asintomático.
2.Los pacientes deben recibir tratamiento dentro de las dos semanas del inicio del infarto cerebral.
3.Los pacientes deben tener un déficit neurológico focal que debe persistir al inicio del tratamiento.
4. Los pacientes deben tener un estudio de neuroimagen cerebral (TC o RM) compatible con el diagnóstico clínico de infarto cerebral agudo en el territorio de la arteria cerebral media antes de ser incluido en el estudio.
5. Los pacientes deben tener una puntuación en la escala de ictus NIHSS de 8-20, con al menos dos de estos puntos en las secciones 5 y 6 (déficit motor) en el momento de la inclusión.
6. Inmediatamente antes del ictus, los pacientes deberán tener una puntuación en la ERm ≤ 1 (no síntomas o incapacidad significativa, capaz de realizar todas las actividades habituales).
7. Las mujeres no menopáusicas deberán tener un test de embarazo negativo antes de la inclusión.
8. Obtención de firma de consentimiento informado (tras una explicación detallada de la naturaleza y propósito del estudio, el paciente o su representante legal deberán otorgar su consentimiento a participar mediante la firma del documento de consentimiento informado. En los casos en los que no sea posible el consentimiento del paciente (por ejemplo por disfasia, confusión o alteración del nivel de conciencia), se obtendrá consentimiento informado de su representante legal.

E.4

Principal exclusion criteria

1. Comatose patients. Patients with a score of 2 or more in paragraphs related to the degree of awareness of the scale of the NIH stroke (1a).
2. Evidence on neuroimaging (CT or MRI) of brain tumour, cerebral oedema with midline shift and compression clinically significant ventricles, cerebellar infarction or brainstem, or intraventricular haemorrhage and / or intracerebral or subarachnoid.
3. Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Pre-existing dementia, if it involves disability rated a score of 2 or more in the mRS.
4. Active infection, including patients with HIV, hepatic B, hepatic C, etc.
5. pre-existing dementia
6. Specify health status or any clinical conditions (e.g., life expectancy, co-existing disease) or other characteristics that precludes appropriate diagnosis, treatment or follow-up in the trial.
7. Patients who are participating in another clinical trial.
8. Inability or unwillingness of individual or legal guardian/representative to give written informed consent.

1. Pacientes en coma. Pacientes con una puntuación de 2 o más en los ítems de la escala NIHSS relacionados con nivel de conciencia (1a).
2. Evidencia en las pruebas de neuroimagen (TC or RM) de tumor cerebral, edema cerebral con desplazamiento de línea media y compresión significativa de los ventrículos, infarto cerebeloso o de troncoencéfalo, hemorragia intraventricular, intraparenquimatosa o subaracnoidea.
3. Consumo habitual de drogas o de alcohol que, en opinión del investigador, pudiera interferir la adherencia a las visitas del estudio.
4. Infección activa, incluyendo pacientes con VIH, hepatitis B, hepatitis C, etc.
5. Demencia pre-existente.
6. Cualquier condición clínica (esperanza de vida, enfermedades concomitantes) u otras circunstancias que interfieran en el proceso diagnóstico adecuado, tratamiento o seguimiento del ensayo clínico.
7. Pacientes que se encuentren participando en otro ensayo clínico.
8. La incapacidad o falta de voluntad por parte del representante legal del paciente para dar consentimiento informado por escrito, en los casos en los que el paciente no pueda firmar su propio consentimiento informado.

E.5 End points

E.5.1

Primary end point(s)

Safety. The safety of mesenchymal stem cells from adipose tissue will be assessed using the following parameters

- Adverse events (AEs) reported spontaneously or in response to questions not addressed. Serious adverse events (SAES). These will be recorded in each visit during all the study period.

- Neurological and systemic complications: deteriorating stroke, stroke recurrences, brain oedema, seizures, hemorrhagic transformation, respiratory infections, urinary tract infections, deep venous thrombosis, pulmonary embolism, gastrointestinal haemorrhage. These will be recorded in each visit during all the study period.

Seguridad. Se evaluará la seguridad de las células troncales alogénicas procedentes de tejido adiposo mediante los siguientes parámetros:

-Efectos adversos (EA) referidos espontáneamente o en respuesta a cuestionarios. Efectos adversos graves (EAG). Se registran en cada visita durante todo el período de estudio.

-Complicaciones neurológicas y sistémicas: ictus progresivo, recurrencias, edema cerebral, crisis comiciales, transformación hemorrágica, infección respiratoria, infección del tracto urinario, trombosis venosa profunda, embolia pulmonar, hemorragia gastrointestinal... Su presencia será evaluada en cada visita durante el periodo de estudio

E.5.1.1

Timepoint(s) of evaluation of this end point

It will be evaluate at each visit during all the study period: (V0) screening; (V1) baseline; (V2) 2-hours after study drug administration; (V3) 24 hours, (V4) day 7 or hospital discharge and (V5) 3 months.

Serán evaluados en cada visita durante todo el periodo del estudio: (V0) screening, 8V1) basal, (V2) dos horas tras la administracion de la medicacion, (V3) 24 horas, (V4) dia 7 o alta hospitalaria y 8V5) 3 meses.

E.5.2

Secondary end point(s)

Efficacy:

- Modified Rankin Scale (mRS): success is considered positive (patients with no or minimal disability) when the patient obtains a score of 0 or 1, and failure, when you get a score of 2 to 6.

- NIH Stroke Scale: success is considered positive (patients without neurological deficit or with minimal deficit) when the patient has a total score of the NIH stroke scale of 0 to 1, and failure, when the score is between 2 and 42.

- Infarct Size: indicates the total volume of infarction in neuroimaging (MRI) at day 7 and at 3 months.

- Biochemical markers of brain repair: VEGF, BDNF, MMP-9.

Eficacia:

- Escala de Rankin modificada (ERm) (apéndice C): Se medirá en las visitas de día 7 y mes 3.

- Escala de ictus NIH (NIHSS) (Apéndice B): Se medirá en todas las visitas del estudio.

- Tamaño del infarto: indica el volumen total del infarto en neuroimagen (RM) en el día 7 y a los 3 meses. Se medirá en las visitas de día 7 y mes 3.

- Marcadores bioquímicos de reparación cerebral: VEGF, BDNF, MMP-9. Se medirán en las visitas basal, día 7 y mes 3.

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy:

- Modified Rankin Scale (mRS): It will be measured at day 7 and at month 3.

- Barthel Index: It will be measured at day 7 and at month 3.

- NIH Stroke Scale: It will be measured at all the scheduled visits. (V0) screening; (V1) baseline; (V2) 2-hours after study drug administration; (V3) 24 hours, (V4) day 7 or hospital discharge and (V5) 3 months.

- Infarct Size: It will be measured at day 7 and at month 3.

- Biochemical markers of brain repair:They will be measured at baseline, day 7 and month 3.

Eficacia:

- Escala de Rankin modificada (MRS): Se medirá el día 7 y en el mes 3.

- Índice de Barthel: Se medirá el día 7 y en el mes 3.

- Escala NIH Stroke: Se mide en todas las visitas programadas. (V0) de detección; (V1) de referencia; (v2) 2 horas después de la administración del fármaco del estudio; (V3) las 24 horas, (V4) el día 7 o alta del hospital y (V5) a 3 meses.

- El tamaño del infarto: Se medirá el día 7 y en el mes 3.

- Los marcadores bioquímicos de la reparación del cerebro: Se les midió al inicio, el día 7 y de 3 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)

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

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

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

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

Last visit of the last subject undergoing the trial

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

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)

It is a pilot clinical trial. The results will develop a more comprehensive study

Este es un estudio piloto. Los resultados se se desarrollaran en un estudio más completo

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

2012-07-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-03

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

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