Clinical Trials Register

Summary
EudraCT Number:	2020-001505-22
Sponsor's Protocol Code Number:	BST-COVID-01
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:	2020-04-27
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

2020-001505-22

A.3

Full title of the trial

Double-blind, randomized, parallel, placebo-controlled pilot clinical trial, nested in a prospective cohort observational study, for the evaluation of the efficacy and safetyof two doses of WJ-MSC in patients with acute respiratory distress syndrome secondary to infection by COVID-19

Ensayo clínico piloto anidado en un estudio observacional de cohorte prospectivo, doble ciego, randomizado, paralelo y controlado con placebo para la evaluación de la eficacia y seguridad de dos dosis de MSC,WJ en pacientes con síndrome de distrés respiratorio agudo secundario a infección por COVID-19

A.3.1

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

Efficacy and safety evaluation of umbilical cord mesenchymal stem cells for the treatment of patients with respiratory failure due to coronavirus (COVID-19)

Evaluación de eficacia y seguridad de las células madre mesenquimales de cordón umbilical para el tratamiento de pacientes con insuficiencia respiratoria por coronavirus (COVID-19)

A.3.2

Name or abbreviated title of the trial where available

COVIDMES

A.4.1

Sponsor's protocol code number

BST-COVID-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.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	Banc de Sang i Teixits
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	349355735006707
B.5.5	Fax number	34935573503
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	XCEL-UMC-BETA
D.3.4	Pharmaceutical form	Solution for infusion
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	EX VIVO EXPANDED WHARTON'S JELLY DERIVED MESENCHYMAL STEM CELLS
D.3.9.2	Current sponsor code	XCEL-UMC-BETA
D.3.9.3	Other descriptive name	EX VIVO EXPANDED WHARTON'S JELLY DERIVED MESENCHYMAL STEM CELLS
D.3.9.4	EV Substance Code	SUB190865
D.3.10	Strength
D.3.10.1	Concentration unit	IU/kg international unit(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	700000 to 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)	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
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 respiratory distress syndrome

Síndrome de distrés respiratorio agudo

E.1.1.1

Medical condition in easily understood language

Acute respiratory distress

Dificultad respiratoria aguda

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10001052
E.1.2	Term	Acute respiratory distress syndrome
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal 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

All-cause mortality at day 28

Mortalidad por cualquier causa a día 28

E.2.2

Secondary objectives of the trial

1- To assess the safety and feasibility of WJ-MSC administration compared to placebo in the treatment of patients with SARS-CoV-2 infection and ARDS
2- Need for treatment with rescue medication
3- Need and duration of mechanical ventilation
4- Ventilator free days
5- Evolution of PaO2 / FiO2 ratio at 3, 5, 7, 14, 21 and 28 days after starting treatment
6- Evolution of the SOFA index at 3, 5, 7, 14, 21 and 28 days after starting treatment
7- Evolution of the APACHE II score at 3, 5, 7, 14, 21 and 28 days after starting treatment
8- Duration of hospitalization
9- Evolution of disease biomarkers: RT-PCR, LDH, D-dimer and Ferritin at 3, 5, 7, 14, 21 y 28 after starting treatment
10- Evolution of markers of immune response (leucocyte count, neutrophils) at 3, 5, 7, 14, 21 y 28 days after starting treatment

1- Seguridad y factibilidad de la administración de WJ-MSC en comparación con placebo en el tratamiento de pacientes con infección por SARS-CoV-2 y SDRA.
2- Necesidad de uso de medicación de rescate
3- Necesidad y duración de ventilación mecánica
4- Días libres de ventilación mecánica
5- Índice de oxigenación (PaO2/FiO2) basal y al día 3, 5, 7, 14, 21 y 28 post inicio del tratamiento
6- Evaluación del índice SOFA basal y al día 3, 5, 7, 14, 21 y 28 post inicio del tratamiento
7- Evaluación de la puntuación APACHE II basal y al día 3, 5, 7, 14, 21 y 28 post inicio del tratamiento
8- Duración de la hospitalización en la UCI
9- Marcadores de la evolución de la enfermedad: RT-PCR, LDH, Dímero D y ferritina basal y al día 3, 5, 7, 14, 21 y 28 post inicio del tratamiento
10- Respuesta inmune (recuento leucocitos y neutrófilos,) basal y al día 3, 5, 7, 14, 21 y 28 post inicio del tratamiento

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Additional Objectives
1- Analysis of subpopulations of lymphocytes and immunogobulins
2- Evaluation of the in vitro response of the receptor lymphocytes at different periods using commercial viral antigens (Miltenyi Botech)
3- Study of reactivity against SARS-CoV-2 peptides using ELISPOT
4- Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides
5- Study of the effect of the genetic variability of patients and the SARS-CoV-2 genotype on the evolution of the disease and response to treatment

Objetivos adicionales (siempre que la situación permita obtener las muestras necesarias)
1- Análisis de subpoblaciones de linfocitos e inmunogobulinas
2- Evaluación de la respuesta in vitro de los linfocitos del receptor a diferentes periodos utilizando antígenos virales comerciales (Miltenyi Botech).
3- Estudio de reactividad frente a péptidos de SARS-CoV-2 mediante ELISPOT
4- Estudio inmunofenotípico de células de memoria en respuesta a péptidos de SARS-CoV-2
5- Estudio del efecto de la variabilidad genética de los pacientes y el genotipo del SARS-CoV-2 sobre la evolución de la enfermedad y respuesta al tratamiento

E.3

Principal inclusion criteria

1. Participation in the prospective observational epidemiological study CIBERESUCICOVID (PCR for SARS-CoV-2 positive, ICU admission)
2. Moderate acute respiratory distress (Berlin criteria definition with 100 mmHg < PaO2/FiO2 ≤ 200 mmHg)
3. Male or female, aged 18 to 70 years old
4. Signed informed consent by the patient or by a legal representative

1. Participación en el estudio epidemiológico observacional prospectivo CIBERESUCICOVID (PCR para SARS-CoV-2 positivo, ingreso en UCI)
2. Distrés respiratorio agudo moderado (definición de Berlín con 100 mmHg < PaO2/FiO2 ≤ 200 mmHg)
3. Paciente de 18 a 70 años, ambos sexos
4. Firma del consentimiento informado por parte del paciente o por un representante válido

E.4

Principal exclusion criteria

1. Expected survival less than 3 days
2. Treatment with immunosuppressive drugs (tocilizumab, sarilumab) with corticosteroids being allowed
3. Neoplastic disease either active or without complete remission
4. Immunosuppressed patients (except treatment with corticosteroids for respiratory distress)
5. Pregnant or lactating women
6. Participation in another clinical trial with an experimental drug in the last 30 days
7. Other pathologies that, in medical judgment, contraindicate participation in the study

1. Supervivencia esperada menor de 3 días
2. Tratamiento con fármacos inmunosupresores (tocilizumab, sarilumab) estando permitidos los corticosteroides
3. Enfermedad neoplásica activa o sin remisión completa
4. Pacientes inmunodeprimidos (excepto tratamiento con corticoides para el distrés respiratorio)
5. Mujeres embarazadas o lactantes
6. Participación en otro estudio clínico con un fármaco experimental en los últimos 30 días
7. Otras patologías que, a criterio médico, contraindiquen la participación en el estudio

E.5 End points

E.5.1

Primary end point(s)

Number of patients who died on day +28, by treatment group

Número de pacientes fallecidos a día +28, por grupo de tratamiento

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 28

Día 28

E.5.2

Secondary end point(s)

1- Safety and feasibility. Safety will be assessed by physical examination, vital signs, laboratory data, and adverse events throughout the study, by treatment group. Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date and the number of patients that can be treated within 2 days of the request for treatment.
2- Number and percentage of patients who, after the start of treatment, required rescue medication at day +28
3- Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28
4- Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, up to day +28
5- Variation of the oxygenation index (PaO2 / FiO2)
6- Variation of the score of the SOFA Index
7- Variation of APACHE II score
8- Days of stay in the ICU from the day of admission until discharge to day 28, or date of death if earlier, by treatment group.
9- Variation in the values of the markers of evolution of the disease (RT-PCR, LDH, D-dimer and Ferritin)
10- Variation in the count and percentage of leukocytes and neutrophils

1. Seguridad y eficacia. La seguridad se evaluará mediante exploración física, constantes vitales, datos de laboratorio y acontecimientos adversos a lo largo del estudio, por grupo de tratamiento. La factibilidad se evaluará mediante el tiempo transcurrido desde la solicitud del tratamiento por parte del centro hospitalario hasta la fecha de entrega y el número de pacientes que pueden tratarse dentro de los 2 días siguientes a la solicitud del tratamiento.
2. Número y porcentaje de pacientes que, tras el inicio del tratamiento, han requerido medicación de recate a día +28, por grupo de tratamiento
3. Número de días que el paciente requiere ventilación mecánica invasiva desde el inicio del tratamiento hasta día +28, por grupo de tratamiento.
4. Días posteriores al tratamiento en el que el paciente permanece vivo y libre de ventilación mecánica invasiva, hasta día +28, por grupo de tratamiento.
5. Variación del Índice de oxigenación (PaO2/FiO2)
6. Variación de la puntuación del Índice SOFA
7. Variación de la puntuación APACHE II
8. Días de estancia en la UCI desde el día de ingreso hasta el alta a día 28, o fecha de la muerte si es antes, por grupo de tratamiento.
9. Variación en los valores de los marcadores de evolución de la enfermedad
10. Variación en el recuento y porcentaje de leucocitos y neutrófilos

E.5.2.1

Timepoint(s) of evaluation of this end point

At day 3, 5, 7, 14, 21 and 28 after starting treatment with respect to the baseline value, by treatment group

A día 3, 5, 7, 14, 21 y 28 post inicio del tratamiento respecto al valor basal, por grupo de tratamiento.

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

Yes

E.6.13.1

Other scope of the trial description

Nested trial in a prospective cohort observational study

Ensayo clínico piloto anidado en un estudio observacional de cohorte prospectivo

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

New indication (ARDS)

Nueva indicación (SDRA)

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Ensayo clínico piloto anidado en un estudio observacional de cohorte prospectivo

Nested in a prospective cohort observational study

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

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

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

LVLS

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

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-04-27.

Yes

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

The patients will be admitted to the ICU. If needed,consent will be requested from their legal representative, but if at any point in the follow-up the patient is able to give his consent, he will be asked to reconsider his participation in the study

Los pacientes estarán ingresados en la UCI. Puede requerirse consentimiento a su representante legal, pero si en algún momento del seguimiento el paciente es capaz de dar su consentimiento, se le pedirá que reconsienta su participación en el estudio

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)

After day 28 (end of the trial) patients willl be followed-up to month 12 as part of the long-term safety and efficacy follow-up.

Después de la finalización del estudio a dís 28, se seguirá a los pacientes hasta el mes 12 como parte de 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

2020-04-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-22

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