Clinical Trials Register

Summary
EudraCT Number:	2017-003989-27
Sponsor's Protocol Code Number:	PROLONGSTEM
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:	2018-10-25
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

2017-003989-27

A.3

Full title of the trial

PROLONGSTEM: HepaStem Long-Term Safety Registry
Registry for patients who have been administered HepaStem

PROLONGSTEM: Registro de seguridad a largo plazo de HepaStem
Registro para pacientes a los que se administró HepaStem

A.3.1

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

PROLONGSTEM is a long term follow-up study of all the patients who have received at least one infusion of HepaStem

PROLONGSTEM es un estudio de seguimiento a largo plazo de todos los pacientes que han recibido al menos una inyección de HepaStem

A.4.1

Sponsor's protocol code number

PROLONGSTEM

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/313/2013

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Promethera Biosciences
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Promethera Biosciences
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Promethera Biosciences
B.5.2	Functional name of contact point	Clinical Research Department
B.5.3	Address:
B.5.3.1	Street Address	Rue Granbonpré, 11
B.5.3.2	Town/ city	Mont-Saint-Guibert
B.5.3.3	Post code	B-1435
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+32 10 394300
B.5.5	Fax number	+32 10 394301
B.5.6	E-mail	clinic@promethera.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	Yes
D.2.5.1	Orphan drug designation number	OD/101/07-039/07-057-058- 059-060-061-062-063/13
D.3 Description of the IMP
D.3.1	Product name	HepaStem
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	Yes
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	heterologous human adult liver-derived progenitor cells
D.3.9.2	Current sponsor code	HHALPC
D.3.9.3	Other descriptive name	HHALPC
D.3.9.4	EV Substance Code	SUB122824
D.3.10	Strength
D.3.10.1	Concentration unit	million organisms/ml million organisms/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	10 to 50
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	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	Yes
D.3.11.3.5.1	CAT classification and reference number	Somatic Cell Therapy Product (EMA/CAT/243155/2011) - Treatment of inborn errors of liver metabolism Tissue engineered product (EMA/CAT/391889/2016) - treatment of fibroinflammatory liver diseases.
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

This study will include all patients having received at least one infusion of the Investigational Medicinal Product (IMP) HepaStem HHALPC during a previous interventional clinical study conducted by Promethera Biosciences including patients suffering from urea cycle disorders (UCD), Crigler-Najjar (CN) and Fibro-inflammatory liver diseases

Este estudio incluirá a todos los pacientes que hayan recibido al menos una inyección del producto en fase de investigación clínica (PEI), HepaStem HHALPC, durante un estudio clínico de intervención previo realizado por Promethera Biosciences incluyendo pacientes con trastornos del ciclo de la urea (UCD), Crigler-Najjar (CN) y Enfermedades hepáticas fibroinflamatorias

E.1.1.1

Medical condition in easily understood language

This study is a long term safety follow-up for all the patients that have received at least one dose of HepaStem: patients suffering from UCD, CN and fibro-inflammatory liver diseases

Este estudio es un seguimiento de seguridad a largo plazo para todos los pacientes que han recibido al menos una dosis de HepaStem: pacientes con UCD, CN y enfermedades hepáticas fibroinflamatorias

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10021601
E.1.2	Term	Inborn error of metabolism NOS
E.1.2	System Organ Class	100000004850

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10008954
E.1.2	Term	Chronic liver disease and cirrhosis
E.1.2	System Organ Class	100000004871

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10049844
E.1.2	Term	Acute liver failure
E.1.2	System Organ Class	100000004871

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10013373
E.1.2	Term	Disorders of urea cycle metabolism
E.1.2	System Organ Class	200000003094

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Longitudinal evaluation of the long-term safety post-HepaStem administration.

Evaluación longitudinal de la seguridad a largo plazo después de la administración de HepaStem.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. All patients having received at least one infusion of HepaStem during a previous interventional clinical study conducted by Promethera Biosciences.
2. Written Informed Consent.
For a patient who is a minor (according to the national regulations), and for adult patients legally incapable: the parents or legal representative have provided a signed informed consent before enrolment. If the patient is capable of signing, he/she is required to sign an assent in parallel.
For adult patient (legally capable): patient has provided a written informed consent before enrolment.

1. Todos los pacientes que recibieron al menos una inyección de HepaStem durante un estudio clínico de intervención previo realizado por Promethera Biosciences.
2. Consentimiento informado escrito.
Para un paciente que es menor de edad (de acuerdo con las reglamentaciones nacionales) y para pacientes adultos legalmente incapaces: los padres o representante legal han proporcionado un consentimiento informado firmado antes de la inscripción. Si el paciente es capaz de firmar, se requiere que firme un consentimiento en paralelo.
Para pacientes adultos (con capacidad legal): el paciente ha proporcionado un consentimiento informado por escrito antes de la inscripción.

E.4

Principal exclusion criteria

1. Patients who received an OLT and completed 6-month FU documentation prior to the start of the PROLONGSTEM study.
2. Patients who have received mature liver cells or stem cells other than HepaStem prior to the start of the PROLONGSTEM study.

1. Pacientes que recibieron un transplante de hígado y documentación completa de estudio de seguimiento de 6 meses antes del inicio del estudio PROLONGSTEM.
2. Pacientes que hayan recibido células hepáticas maduras o células madre distintas de HepaStem antes del inicio del estudio PROLONGSTEM.

E.5 End points

E.5.1

Primary end point(s)

Occurrence of Adverse Events of Specific Interest (AESI):
- Event with fatal outcome (Death)
- Orthotopic Liver Transplantation (OLT) and Outcome.
- Development of Malignancy or unwanted tissue formation in different organs (tumor malignant or not).
- Disease linked to transmission of adventitious agents or reactivation of latent pathogens.
- Any AE which in the opinion of the investigator has a plausible causal relationship to HepaStem.
These AESI should be considered as medically important and reported as SAE.

Ocurrencia de acontecimientos adversos de interés específico (AESI):
- Evento con resultado fatal (Muerte)
- Trasplante de hígado y resultado.
- Desarrollo de tumores malignos o formación de tejido no deseado en diferentes órganos (tumores malignos o no).
- Enfermedad relacionada con la transmisión de agentes adventicios o la reactivación de patógenos latentes.

E.5.1.1

Timepoint(s) of evaluation of this end point

Patients who previously received the IMP HepaStem in the context of an interventional study with HepaStem administration will be followed-up for long-term safety surveillance up to 5 years in this PROLONGSTEM study.

Los pacientes que recibieron previamente el PEI HepaStem en el contexto de un estudio de intervención con administración de HepaStem serán objeto de seguimiento para la vigilancia de la seguridad a largo plazo hasta 5 años en este estudio PROLONGSTEM.

E.5.2

Secondary end point(s)

Not applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable

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

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

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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

LPLV

Ultimo paciente Última visita

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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 2018-10-25.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

Yes

F.3.3.4

Nursing women

Yes

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Paediatric patients (<18 years old)
Adult subjects legally incapable

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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:
This study is a long term follow-up of all patients having received at least one infusion of the Investigational Medicinal Product (IMP) HepaStem HHALPC during a previous interventional clinical study conducted by Promethera Biosciences

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

2018-11-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-10-26

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

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