Clinical Trials Register

Summary
EudraCT Number:	2015-005786-23
Sponsor's Protocol Code Number:	XCEL-SCI-01
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:	2016-03-31
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

2015-005786-23

A.3

Full title of the trial

A phase I/IIa, randomized, double-blind, single-dose, placebo controlled, two-way crossover clinical trial to assess the safety and to obtain efficacy data in intrathecal administration of expanded Wharton?s jelly mesenchymal stem cells in chronic traumatic spinal cord injury

Estudio clínico piloto de fase I/IIa, aleatorizado, doble ciego, cruzado, de dos brazos de tratamiento, dosis única y controlado con placebo para evaluar la seguridad y obtener indicios de eficacia en la administración intratecal de células mesenquimales expandidas de gelatina de Wharton en la lesión medular traumática crónica

A.3.1

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

Safety assessment of cord blood mesenchymal stromal cells in chronic spinal cord injury

Evaluación de la seguridad de células mesenquimales estromales de cordón umbilical en lesión medular crónica

A.3.2

Name or abbreviated title of the trial where available

Wharton?s jelly mesenchymal stem cells for chronic traumatic spinal cord injury

Células mesenquimales de gelatina de Wharton en la lesión medular traumática crónica

A.4.1

Sponsor's protocol code number

XCEL-SCI-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	Banc de Sang i Teixits
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	Banc de Sang i Teixits
B.4.2	Country	Spain
B.4.1	Name of organisation providing support	Instituto Guttmann
B.4.2	Country	Spain
B.4.1	Name of organisation providing support	Fundació la Marató de TV3
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	Banc de Sang i Teixits
B.5.2	Functional name of contact point	Direc Med División Terap Avanzadas
B.5.3	Address:
B.5.3.1	Street Address	Passeig Taulat 116
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08005
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3493557 35 006707
B.5.5	Fax number	+3493557 35 02
B.5.6	E-mail	rucoll@bst.cat

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 mesenq troncales adultas alogénicas de gelatina de Wharton del CU expandidas criopreservadas
D.3.2	Product code	XCEL-UMC-BETA
D.3.4	Pharmaceutical form	Solution for infusion in pre-filled syringe
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	Adult allogeneic expanded and criopreserved umbilical cord WJ-derived mesenchymal stromal cells
D.3.9.2	Current sponsor code	XCEL-UMC-BETA
D.3.9.3	Other descriptive name	MESENCHYMAL STEM CELLS FROM WHARTON JELLY
D.3.9.4	EV Substance Code	SUB27304
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	8000000 to 12000000
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion in pre-filled syringe
D.8.4	Route of administration of the placebo	Intrathecal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic traumatic spinal cord injury

Lesión medular traumática crónica

E.1.1.1

Medical condition in easily understood language

Chronic traumatic spinal cord injury

Lesión de médula espinal traumática crónica

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	18.1
E.1.2	Level	PT
E.1.2	Classification code	10041558
E.1.2	Term	Spinal cord injury thoracic
E.1.2	System Organ Class	10022117 - Injury, poisoning and procedural complications

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 assess the safety of XCEL-UMC-BETA infusion in the treatment of thoracic level complete traumatic chronic spinal cord injury, from 12 month to 5 years evolution.

Evaluar la seguridad de la infusión de XCEL-UMC-BETA en el tratamiento de la lesión medular traumática crónica completa y de nivel torácico, de 12 meses a 5 años de evolución.

E.2.2

Secondary objectives of the trial

- To assess efficacy of XCEL-UMC-BETA infusion in the treatment of thoracic level complete traumatic chronic spinal cord injury, from 12 month to 5 years evolution, by:
a) ASIA assessment
b) Electrophysiology tests (motor and somatosensory evoked potentials. H and F waves)
c) Electrical pain threshold perception
d) Urodynamic testing
e) Anorectal manometry test
- Clinical assessment of XCEL-UMC-BETA infusion in the treatment of thoracic level complete traumatic chronic spinal cord injury, from 12 month to 5 years evolution, by:
a) Numerical scale for neuropathic pain assessment
b) Modified Ashworth scale for spasticity
c) SCIM III scale for functionality
d) Quality of life questionnaire (EUROQOL-5D)
e) Qualiveen questionnaire
- Assessment of changes by magnetic resonance imaging

Indicios de eficacia de la infusión de XCEL-UMC-BETA en el tratamiento de la lesión medular traumática crónica, de 12 meses a 5 años de evolución, mediante:
a) Puntuación ASIA
b) Pruebas electrofisiológicas (potenciales motores y somatosensoriales evocados, y ondas H y F)
c) Umbral de percepción del dolor por corriente eléctrica.
d) Pruebas funcionales de control de la vejiga mediante estudio urodinámico.
e) Estudio funcional del intestino mediante manometría anorectal.
- Evaluación clínica tras infusión de XCEL-UMC-BETA en el tratamiento de la lesión medular traumática crónica, de 12 meses a 5 años de evolución, mediante:
a) Escala Numérica para el dolor neuropático
b) Escala de Ashworth modificada para espasticidad
c) Valoración funcional mediante la escala SCIM III
d) Cuestionario de calidad de vida EUROQOL-5D
e) Cuestionario Qualiveen
- Evaluación de los cambios visualizados por resonancia magnética

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Single spinal cord injury lesion caused by trauma
2. Affected cord segments between T2 and T11, confirmed by magnetic resonance
3. Complete paraplegia (ASIA A)
4. Chronic disease state (between 12 months and 5 years after the injury)
5. Patients from 18 to 65 years of age, both sexes
6. Life expectancy > 2 years
7. Confidence that the patient will attend the follow-up visits.
8. Given informed consent in writing
9. Patient is able to understand the study and its procedures

1. Lesión de médula espinal única de etiología traumática
2. Afectación de los segmentos entre T2 y T11, confirmado por resonancia magnética
3. Paraplejia completa (ASIA A)
4. Estado crónico de la lesión (entre 12 meses y 5 años post lesión medular)
5. Pacientes de ambos sexos entre 18 y 65 años (ambos incluidos)
6. Paciente con expectativa de vida > 2 años
7. Confianza en que el paciente podrá acudir a las visitas de seguimiento del estudio.
8. Consentimiento Informado por escrito del paciente
9. El paciente es capaz de entender la naturaleza del estudio

E.4

Principal exclusion criteria

1. Mechanic ventilation
2. Lesion affecting multiple levels
3. Lesion length superior to 3 spinal cord segments, assessed by magnetic resonance
4. Penetrating trauma affecting the spinal cord
5. Positive serology to HIV, HBV, HCV and or syphilis
6. Pregnant woman or without proper anticonceptive measures according to the investigator, or breath feeding
7. Use of metal implants difficulting the MRI
8. Planned spinal surgery within subsequent 24 month after entering the trial
9. Intrathecal medication or immunossupresive drugs the previous 60 days.
10. Neurodegenerative diseases
11. Significant abnormal laboratory tests that contraindicates patient's participation in the study.
12. Neoplasia within the previous 5 years, or without complete remission
13. Patient with communication difficulties
14. Participation in another clinical trial or treated with an investigational medicinal product the previous 60 days
15. Contraindication for lumbar punction
16. Other pathologic conditions or circumstances that difficult participation in the study according to medical criteria
17. The patient does not accept to be followed-up for a period that could exceed the clinical trial length

(*) Allowed anticonceptive methods are: hormones, intrauterine dispositive, barrier methods, voluntarily sterilization or menopause >1year duration.

1. Ventilación mecánica
2. Lesión afectando a múltiples niveles
3. Longitud de la lesión de más de 3 segmentos medulares medido por resonancia magnética
4. Traumatismo penetrante con afectación de la médula espinal
5. Serología positiva para HIV, VHB, VHC y/o lúes
6. Mujeres embarazadas o mujeres sin cobertura anticonceptiva eficaz según criterio del investigador (*), y mujeres en periodo de lactancia
7. Instrumentación espinal compleja que dificulte la evaluación de la lesión por resonancia magnética
8. Intervención quirúrgica planeada en la zona de la lesión dentro de los siguientes 24 meses de la inclusión en el estudio
9. Tratamiento con medicación intratecal o inmunosupresora (incluidos los corticoides sistémicos) dentro de los 60 días anteriores a la inclusión en el estudio.
10. Enfermedades neurodegenerativas
11. Análisis hematológicos y bioquímicos con alteraciones significativas que contraindiquen la participación en el estudio.
12. Enfermedad neoplásica detectada en los últimos cinco años o sin remisión completa.
13. Dificultades de comunicación con los evaluadores
14. Participación simultánea en otro ensayo clínico o tratamiento con otro producto en fase de Investigación en los 60 días previos a la inclusión en el estudio.
15. Contraindicación para la punción lumbar
16. Otras patologías o circunstancias que puedan comprometer la participación del paciente en el estudio según criterio médico.
17. Negación del paciente a ser seguido por un periodo que excede el ensayo clínico en sí.
(*) Los métodos anticonceptivos eficaces que se contemplaran en el protocolo son los hormonales, el dispositivo intrauterino (DIU), los métodos de barrera, la esterilización voluntaria o que la paciente tenga la menopausia de >1año de duración.

E.5 End points

E.5.1

Primary end point(s)

- Safety assessment through adverse events, physical exam, vital signs and laboratory data.

- Evaluación de la seguridad mediante exploración física, constantes vitales, datos de laboratorio y acontecimientos adversos.

E.5.1.1

Timepoint(s) of evaluation of this end point

month 12

mes 12

E.5.2

Secondary end point(s)

- Efficacy will be assessed though changes in respect to basal parameters for each period:
a) ASIA punctuation at 1, 3 and 6 months (1, 3, 6, 7, 9 and 12 months of the study)
b) Electrophysiology tests (motor and somatosensory evoked potentials. H and F waves) at 1, 3 and 6 months (1, 3, 6, 7, 9 and 12 months of the study)
c) Electrical pain threshold perception at 1, 3 and 6 months (1, 3, 6, 7, 9 and 12 months of the study)
d) Urodynamic testing at 6 months (6 and 12 months of the trial)
e) Anorectal manometry test at 6 months (6 and 12 months of the trial)
- Assessment of clinical changes at 1, 3 and 6 months of each period (1, 3, 6, 7, 9 and 12 months of the study), in respect to basal parameters, for:
a) Numerical scale for neuropathic pain assessment
b) Modified Ashworth scale for spasticity
c) SCIM III scale for functionality
d) Quality of life questionnaire (EUROQOL-5D)
e) Qualiveen questionnaire (at month 6 of each period) (6 and 12 months of the trial)
- Changes by magnetic resonance imaging on the size and lesion characteristics at month 6 in respect to basal parameters, for each period (6 and 12 months of the trial)

- La eficacia se evaluará mediante los cambios respecto al basal de las siguientes pruebas, en cada periodo:
a) Puntuación ASIA al 1, 3 y 6 meses
b) Pruebas electrofisiológicas (potenciales motores y somatosensoriales evocados, y ondas H y F) a los 1,3 y 6 meses
c) Umbral de percepción del dolor por la corriente eléctrica a los 1, 3 y 6 meses
d) Pruebas funcionales de control de la vejiga mediante estudio urodinámico a los 6 meses
e) Estudio funcional del intestino mediante manometría anorectal a los 6 meses
- Los cambios clínicos se evaluaran a los 1, 3 y 6 meses, respecto al basal, para los siguientes parámetros y para cada periodo:
a) Escala numérica para el dolor neuropático
b) Escala de Ashworth modificada para espasticidad
c) Escala de valoración funcional SCIM III
d) Test de calidad de vida EUROQOL-5D
e) Cuestionario Qualiveen (a los 6 meses de cada periodo)
- Los cambios en la neuroimagen se evaluarán con resonancia magnética mediante cambios en el tamaño y características de la lesión a los 6 meses, respecto al basal, para cada periodo de tratamiento

E.5.2.1

Timepoint(s) of evaluation of this end point

month 12

mes 12

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

Yes

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

Yes

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

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

última visita del último 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)

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)

All patients wil be periodically followed-up, at their standard point of care, after their participation in the trial to confirm long-term safety and effciacy

Todos los pacientes seguirán controles periódicos por su médico, tras su participación en el estudio para confirmar la seguridad y eficacia a largo plazo

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

2016-04-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-18

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

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