Clinical Trials Register

Summary
EudraCT Number:	2017-003989-27
Sponsor's Protocol Code Number:	PROLONGSTEM
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-04-12
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

France - ANSM

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 : Registre sur la sécurité à long terme d’HepaStem
Registre pour les patients qui ont été perfusés avec 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 est une étude de suivi à long terme de tous les patients qui ont reçu au moins une perfusion d'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	Welcome desk
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	regulatory@promethera.com

D. IMP Identification

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

Cette étude enrollera tous les patients ayant reçu au moins une infusion du médicament expérimental (ME) HepaStem (cellules souches allogéniques isolées du foie humain adulte), au cours d’une précédente étude clinique interventionnelle menée par Promethera Biosciences.

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

Cette étude est un suivi de la sécurité à long terme pour tous les patients ayant reçu au moins une dose d'HepaStem: patients souffrant d'UCD, de CN et de maladies hépatiques fibro-inflammatoires

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.

Évaluation longitudinale de la sécurité à long terme d’HepaStem après son administration.

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- Tous les patients ayant reçu au moins une infusion d’HepaStem au cours d’une précédente étude clinique interventionnelle menée par Promethera Biosciences.
2- Signature du consentement éclairé.
Patients mineurs (conformément à la réglementation nationale) et adultes incapables : signature du formulaire de consentement éclairé par les parents ou le représentant légal avant l’inclusion. Si le patient est en capacité de signer, il devra signer un consentement en parallèle.
Patients adultes (capables) : signature du consentement éclairé avant l’inclusion.

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- Patients ayant bénéficié d’une transplantation hépatique orthotopique et d’un suivi de 6 mois (documenté) avant le début de PROLONGSTEM
2- Patients ayant reçu des cellules hépatiques matures ou des cellules souches autres qu’HepaStem avant le début de 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.

Survenue d’effets indésirables d’intérêt spécifique (AESI) :
- Événement d’issue fatale (décès)
- Transplantation hépatique orthotopique et issue
- Développement d’un cancer ou de tissu indésirable dans différents organes (tumeur maligne ou non)
- Maladie liée à la transmission d’agents fortuits ou réactivation de pathogènes latents
- Tout EI qui, de l’avis de l’investigateur, pourrait avoir un lien de causalité avec HepaStem

Ces AESI devront être considérés comme médicalement significatifs et être déclarés en tant qu’EIG.

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.

Dans le cadre cette étude PROLONGSTEM, les patients ayant reçu de l'HepaStem lors d’une étude interventionnelle portant sur ce ME feront l’objet d’un suivi de sécurité à long terme de 5 ans maximum.

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

LVLP

dernière visite du dernier patient

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 2018-04-12.

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

Patients pédiatriques (<18 ans)
Sujets adultes légalement incapables

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

Non applicable:
Cette étude est un suivi à long terme de tous les patients ayant reçu au moins une perfusion du médicament expérimental (ME) HepaStem HHALPC lors d'une étude clinique interventionnelle précédente dirigé par 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

2018-06-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-09-05

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

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