Clinical Trials Register

Summary
EudraCT Number:	2022-000279-38
Sponsor's Protocol Code Number:	ENDOSC-CLAD
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:	2022-03-23
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

2022-000279-38

A.3

Full title of the trial

AN OPEN LABEL, RANDOMISED, CONTROLLED CLINICAL TRIAL TO ASSESS THE SAFETY OF ENDOBRONCHIAL ADMINISTRATION OF ALLOGENEIC MESENCHYMAL STROMAL CELLS IN PATIENTS WITH LUNG TRANSPLANT CHRONIC REJECTION: Study ENDOSC-CLAD

ENSAYO CLÍNICO ABIERTO, ALEATORIZADO Y CONTROLADO PARA EVALUAR LA SEGURIDAD DE LA ADMINISTRACIÓN INTRABRONQUIAL DE CÉLULAS DEL ESTROMA MESENQUIMAL ALOGÉNICAS EN PACIENTES CON RECHAZO CRÓNICO DE TRASPLANTE DE PULMÓN: Estudio ENDOSC-CLAD

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

ENDOSC-CLAD

A.4.1

Sponsor's protocol code number

ENDOSC-CLAD

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	FUNDACION INVESTIGACION BIOMEDICA HOSPITAL PUERTA DE HIERRO MAJADAHONDA
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	Hospital Universitario Puerta de Hierro
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	SCReN - HOSPITAL PUERTA DE HIERRO MAJADAHONDA
B.5.2	Functional name of contact point	Ana Velasco
B.5.3	Address:
B.5.3.1	Street Address	c/ Joaquin 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	(+34)911917867
B.5.6	E-mail	avelasco.idiphim@gmail.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	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 mesenchymal stem cells
D.3.2	Product code	MSC
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	Endotracheopulmonary use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	HUMAN MESENCHYMAL STEM CELLS
D.3.9.2	Current sponsor code	MSC
D.3.9.3	Other descriptive name	HUMAN MESENCHYMAL STEM CELLS
D.3.9.4	EV Substance Code	SUB191337
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1400000 to 2800000
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	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

PATIENTS WITH LUNG TRANSPLANT CHRONIC REJECTION

PACIENTES CON RECHAZO CRÓNICO DE TRASPLANTE DE PULMÓN

E.1.1.1

Medical condition in easily understood language

PATIENTS WITH LUNG TRANSPLANT CHRONIC REJECTION

PACIENTES CON RECHAZO CRÓNICO DE TRASPLANTE DE PULMÓN

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.1
E.1.2	Level	PT
E.1.2	Classification code	10083303
E.1.2	Term	Bronchiolitis obliterans syndrome
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10051604
E.1.2	Term	Lung transplant rejection
E.1.2	System Organ Class	10021428 - Immune 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 assess the safety of endobronchial administration of allogenic MSCs in patients with BO.

Evaluar la seguridad de la administración intrabronquial de MSC alogénicas en pacientes con BOS.

E.2.2

Secondary objectives of the trial

To assess the efficacy of endobronchial administration of allogenic MSCs in the BO progression.

Evaluar la eficacia de la administración intrabronquial de MSC alogénicas en pacientes con BOS.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients should have signed written informed consent.
2. Adult patients ≥18 years of age at the time of enrolment
3. Patients recipients of a uni or bipulmonary transplant
4. An established diagnosis of BOS ≧ 0p (FEV1≤90% and / or FEF 25-75% ≤ of the baseline value with no other justifying cause) in the last 6 months.

1. Los pacientes deben haber firmado un consentimiento informado por escrito.
2. Pacientes adultos ≥18 años de edad en el momento de la inscripción
3. Pacientes receptores de un trasplante uni o bipulmonar
4. Diagnóstico establecido de BOS ≧ 0p (FEV1≤90% y/o FEF 25-75% ≤ del valor basal sin otra causa que lo justifique) en los últimos 6 meses.

E.4

Principal exclusion criteria

1. History of lobar transplantation
2. History of heart-lung transplantation
3. Active infection at the time of inclusion.
4. Active Acute Rejection not treated at the time of inclusion.
5. Oncological history (except cutaneous basal cell or carcinoma in situ)
6. Systemic autoimmune diseases.
7. Active HIV / HBV / HCV infection (confirmed by serology or PCR)
8. Proximal airway stenosis
9. Pregnancy
10. Performance status 3 or 4 (confined to bed or chair for more than 50% of waking hours, able only to perform some self-care activities)
11. Estimated survival less than 3 months.
12. Known hypersensitivity to components used in the production of allogeneic SCCs.
13. Any circumstance that, in the opinion of the investigator, compromises the patient's ability to participate in the clinical trial.

1. Historia del trasplante lobular
2. Historia del trasplante de corazón y pulmón
3. Infección activa en el momento de la inclusión.
4. Rechazo agudo activo no tratado en el momento de la inclusión.
5. Historia oncológica (excepto basocelular cutáneo o carcinoma in situ)
6. Enfermedades autoinmunes sistémicas.
7. Infección activa por VIH/VHB/VHC (confirmada por serología o PCR)
8. Estenosis de la vía aérea proximal
9. Embarazo
10. Estado funcional 3 o 4 (confinado a la cama o silla durante más del 50 % de las horas de vigilia, capaz solo de realizar algunas actividades de cuidado personal)
11. Supervivencia estimada inferior a 3 meses.
12. Hipersensibilidad conocida a los componentes utilizados en la producción de SCC alogénicos.
13. Cualquier circunstancia que, a juicio del investigador, comprometa la capacidad del paciente para participar en el ensayo clínico.

E.5 End points

E.5.1

Primary end point(s)

- Incidence of early onset (24h) adverse events following MSCs administration: desaturation, hypotension, radiological infiltrates, fever or changes in oxygen therapy requirements.
- Incidence of adverse events of special interest since randomization: lower respiratory tract infections, acute rejection (as defined by the presence of A1-A4 o B1R, B2R in biopsy), BO worsening (as measured by >10% decline in FEV1 from baseline).

- Incidencia de eventos adversos de aparición temprana (24h) tras la administración de MSC: desaturación, hipotensión, infiltrados radiológicos, fiebre o cambios en los requerimientos de oxigenoterapia.
- Incidencia de eventos adversos de especial interés desde la aleatorización: infecciones del tracto respiratorio inferior, rechazo agudo (definido por la presencia de A1-A4 o B1R, B2R en la biopsia), empeoramiento de BO (medido por una disminución de >10 % en FEV1 desde el inicio ).

E.5.1.1

Timepoint(s) of evaluation of this end point

24 hours following MSCs administration

24 horas tras la administración de MSC

E.5.2

Secondary end point(s)

- Mean changes in FEV1 at 12-month from baseline.
- Proportion of patients with >10% decrease in FEV1 from baseline.
- Time to a >10% decrease in FEV1 from baseline.
- Proportion of patients progressing to grade 3 BO (as defined by a FEV1 below 50% from best value post-transplant).
- Mean changes in FVC from baseline to 12-month
- All-cause mortality rate
- Re-transplant or CLAD-related mortality rate.
- Rate of acute rejection (as defined by the presence of A1-A4 o B1R, B2R in biopsy) at any time during the 12-month follow up period.
- Incidence of presence of specific antibodies against donor HLA.
- CLAD progression, as defined by > 10% decline in FEV1 in two consecutive time-points
- Mean changes in the 6-min walking test at any visit time.
- Mean changes in the mMRC Scale at 12-month
- Total hospitalization days during the 12-month follow-up period.
- Proportion of patients requiring ambulatory oxygen therapy.

- Cambios medios en el FEV1 a los 12 meses desde el inicio.
- Proporción de pacientes con una disminución >10 % del FEV1 desde el inicio.
- Tiempo hasta una disminución de >10 % en el FEV1 desde el inicio.
- Proporción de pacientes que progresan a BO de grado 3 (según lo definido por un FEV1 por debajo del 50 % del mejor valor después del trasplante).
- Cambios medios en la CVF desde el inicio hasta los 12 meses
- Tasa de mortalidad por todas las causas
- Tasa de mortalidad por retrasplante o CLAD.
- Tasa de rechazo agudo (definido por la presencia de A1-A4 o B1R, B2R en la biopsia) en cualquier momento durante el período de seguimiento de 12 meses.
- Incidencia de presencia de anticuerpos específicos contra HLA del donante.
- Progresión CLAD, definida por > 10 % de disminución en el FEV1 en dos puntos de tiempo consecutivos
- Cambios medios en el test de marcha de 6 min en cualquier momento de la visita.
- Cambios medios en la escala mMRC a los 12 meses
- Total de días de hospitalización durante el período de seguimiento de 12 meses.
- Proporción de pacientes que requieren oxigenoterapia ambulatoria.

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months from baseline

12 meses desde el inicio

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

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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

tratamiento estándar

standar of care

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

Completion of the 12-month follow-up visit

Completar la visita de seguimiento de los 12 meses

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)

None

Nada

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

2022-11-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-07-08

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

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