Clinical Trials Register

Summary
EudraCT Number:	2014-005613-24
Sponsor's Protocol Code Number:	CME-LEM3
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:	2015-06-01
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2014-005613-24

A.3

Full title of the trial

Intrathecal administration (pattern 100/3) of expanded autologous adult bone marrow mesenchymal troncal cells in established chronic spinal cord injuries

Administración intratecal (pauta 100/3) de células mesenquimales troncales adultas autólogas de médula ósea expandidas en lesiones de la medula espinal crónicamente establecidas

A.3.1

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

Administration of expanded autologous adult bone marrow mesenchymal cells in established chronic spinal cord injuries

Administración de células mesenquimales adultas autólogas de médula ósea expandidas en lesiones de la medula espinal crónicamente establecidas

A.4.1

Sponsor's protocol code number

CME-LEM3

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 Investigación Biomédica Hospital Universitario Puerta de Hierro
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	Instituto de Salud Carlos III
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	Fundación Investigación Biomédica Hospital Universitario Puerta de Hierro
B.5.2	Functional name of contact point	Fundación Investigación Biomédica
B.5.3	Address:
B.5.3.1	Street Address	C/ Joaquín Rodrigo, 2
B.5.3.2	Town/ city	Majadahonda (MADRID)
B.5.3.3	Post code	28222
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34911917760
B.5.5	Fax number	+34911916806
B.5.6	E-mail	apueyo@idiphim.org

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	Células mesenquimales troncales adultas autólogas de medula ósea expandidas
D.3.2	Product code	CME-LEM3
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	Intrathecal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	células mesenquimales troncales adultas autólogas de medula ósea expandidas
D.3.9.2	Current sponsor code	CME-LEM3
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100000000
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)	No
	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Traumatic or ischemic spinal cord injury, chronically established and considered irreversible

Lesión medular de causa traumática o isquémica, crónicamente establecida y considerada irreversible.

E.1.1.1

Medical condition in easily understood language

Traumatic or ischaemic spinal cord injury, chronically established and considered irreversible

Lesión medular de causa traumática o isquémica, crónicamente establecida y considerada irreversible.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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

To analyze the potential clinical efficacy of intrathecal administration, in the subarachnoid space, of in vitro expanded autologous adult bone marrow mesenchymal troncal cells in the treatment of patients with established chronic spinal cord injury (LEM)

Analizar la posible eficacia clínica de la administración intratecal, en espacio subaracnoideo, de células mesenquimales troncales adultas autólogas de la médula ósea expandidas ?in vitro? en el tratamiento de pacientes con lesión medular (LEM) crónicamente establecida.

E.2.2

Secondary objectives of the trial

1.To confirm the safety of this treatment.
2.To study potential changes of neurotrophic factors levels in CSF (BDNF, GDNF, NGF, CNTF, NT3 and NT4) after subarachnoid administration of CME

Se consideran como objetivos secundarios: 1) Confirmar la seguridad del tratamiento, y 2) Estudiar las posibles modificaciones en los niveles de factores neutróficos en LCR (BDNF, GDNF, NGF, CNTF, NT3 y NT4) tras la administración subaracnoidea de CME.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Spinal cord injury (Level A, B, C or D in ASIA scales), clinically stable for at least 6 months prior to study start.
2.Previous studies of Neurophysiology, MRI and Urology to allow useful baseline, in order that they can be compared with the same scans following treatment, and to obtain objective data of potential efficacy.
3.Age between 18 and 70 years.
4.Men and women of childbearing age must compromisse to use contraceptives from the time at which the removal of cells from the bone marrow is performed until 6 months after the MSC last administration by lumbar puncture.
5.Possibility of follow up and ability to perform ambulatory physical therapy throughout all treatment period.
6.Written informed consent, according to the law in force.
7.Hematologic, creatinine, SGOT and SGPT parameters, within the normal range, according to laboratory standards. However, slight modifications that are considered significant in the context of treatment to be performed, according to the criterion of the research team, are accepted.

1) Lesión medular (nivel A, B, C o D en escalas de ASIA), clínicamente estable, al menos en los 6 meses previos al inicio del ensayo.
2) Estudios previos de Neurofisiología, Resonancia Magnética y Urología que permitan contar con valores basales útiles, al objeto de que puedan ser comparados con las mismas exploraciones tras el tratamiento, y poder obtener datos objetivos de posible eficacia.
3) Edad entre 18 y 70 años.
4) Mujeres y hombres en edad fértil deberán comprometerse a utilizar medidas de anticoncepción desde el momento en que se le realice la extracción de células de su médula ósea hasta 6 meses después de la última administración de CME por punción lumbar.
5) Posibilidad de seguimiento evolutivo y de realizar fisioterapia ambulatoria, durante todo el periodo de tratamiento.
6) Consentimiento informado escrito, conforme a la legislación vigente.
7) Parámetros hematológicos y de creatinina, SGOT y SGPT, en rango de normalidad, de acuerdo a los estándares del laboratorio, aceptándose, no obstante, ligeras modificaciones que se consideren no significativas en el contexto del tratamiento a realizar, según criterio clínico del equipo investigador.

E.4

Principal exclusion criteria

1. Age below 18 years or above 70.
2. Pregnancy or lactation.
3. Current neoplastic disease or in the previous 5 years (diagnosed or treated).
4. Patients with systemic disease that represents an added risk to treatment.
5. Alterations in the genetic study performed to discard risk cell transformation in the expansion process.
6. Patients with doubts about possible cooperation in the maintenance physical therapy or in the controls carried out during the study
7. Neurodegenerative disease added.
8. History of substance abuse, psychiatric disease or allergy to protein products used in the process of cell expansion.
9. Positive serology for HIV and syphilis.
10. Active Hepatitis B or Hepatitis C, according to serology analysis.
11. If in the opinion of the researcher there is some other reason why the patient is not considered candidate for the study.

1) Edad inferior a 18 años o superior a 70.
2) Embarazo o lactancia.
3) Enfermedad neoplásica actual o bien en los 5 años previos (diagnosticada o tratada).
4) Pacientes con enfermedad sistémica que se considere puede representar un riesgo añadido al tratamiento.
5) Alteraciones en el estudio genético realizado para descartar riesgo de transformación celular en el proceso de expansión.
6) Pacientes con dudas acerca de su posible cooperación en el mantenimiento de fisioterapia o de controles durante el estudio.
7) Enfermedad neurodegenerativa añadida.
8) Historia de drogadicción, de enfermedad psiquiátrica, o de alergia a los productos proteicos utilizados en el proceso de expansión celular.
9) Serología positiva a HIV y/o sífilis.
10) Hepatitis B o Hepatitis C activa, de acuerdo al análisis de serología.
11) Si en la opinión del investigador existe alguna otra causa por la cual el paciente no se considere candidato al estudio.

E.5 End points

E.5.1

Primary end point(s)

-Changes in ASIA scales and its subsections, as well as in IANR-SCIFRS, PENN, ASHWORTH, EVA, GEFFNER and BDS scales.
-Changes in the neurophysiological records (somato-sensory evoked potentials, motor evoked potentials and EMG).
-Changes in spinal cord morphology in neuroimaging studies (MRI).
-Changes in urodynamic records.

- Modificaciones en las escalas ASIA y sus subapartados, asi como en las escalas IANR-SCIFRS, PENN, ASHWORTH, EVA, GEFFNER y BDS.
- Modificaciones en los registros neurofisiológicos (Potenciales evocados somato- sensoriales, Potenciales evocados motores y EMG).
- Modificaciones de la morfología medular, tras estudio de neuroimagen (RM de alta definición).
- Modificaciones en registros urodinámicos.

E.5.1.1

Timepoint(s) of evaluation of this end point

Efficacy will be assessed taking into account the changes in score of the different scales along the study, compared to the scores before starting treatment, and also comparing neurophysiological and urodynamic records, and marrow morphology baseline data with those obtained in the end of the follow up period (10 months after the start of the treatment).

La eficacia se evaluará teniendo en cuenta la variación en la puntuación de las diferentes escalas a lo largo del estudio, en comparación con las puntuaciones obtenidas antes de iniciar el tratamiento, e igualmente comparando los registros neurofisiológicos y urodinámicos, y los datos de morfología medular considerados como datos basales y los obtenidos al finalizar el periodo de seguimiento (mes 10 tras el inicio de la fase de tratamiento)

E.5.2

Secondary end point(s)

Will be evaluated the changes in neurotrophic factors levels in CSF (BDNF, GDNF, NGF, CNTF, NT3 and NT4), as well as possible adverse effects during CME administration, development of complications and other adverse effects after it and during the follow up period.

Se evaluarán las posibles modificaciones en los niveles de factores neurotróficos en LCR en el curso del tratamiento (BDNF, GDNF, NGF, CNTF, NT3 y NT4), así como los posibles efectos adversos durante la administración de las CME, aparición de complicaciones y otros efectos adversos tras la misma y durante el periodo de seguimiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

During follow up period.

Durante el periodo de seguimiento.

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

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

Yes

E.6.13.1

Other scope of the trial description

Changes in neurotrophic factors levels in CSF (BDNF, GDNF, NGF, CNTF, NT3 and NT4) after MSC subarachnoid administration.

Modificaciones en los niveles de factores neutróficos en LCR (BDNF, GDNF, NGF, CNTF, NT3 y NT4) tras la administración subaracnoidea de CME.

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

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

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

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

LVLS

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

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)

Not applicable

No aplica

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

2015-06-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-09

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials