Clinical Trials Register

Summary
EudraCT Number:	2018-002373-22
Sponsor's Protocol Code Number:	hNSCALSII
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2019-01-21
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-002373-22

A.3

Full title of the trial

Neural Stem Cell Treatment for Amyotrophic Lateral Sclerosis: A multicenter, randomized placebo controlled and biological endpoints clinical Trial

Trattamento con cellule staminali neurali per la sclerosi laterale amiotrofica: uno studio clinico multicentrico, randomizzato controllato da placebo e con endpoint biologici

A.3.1

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

Stem Cell intracerebroventricular Transplantation in Amyotrophic Lateral Sclerosis patients

Trapianto intracerebroventricolare di cellule staminali in pazienti affetti da SLA

A.3.2

Name or abbreviated title of the trial where available

STEMALS

A.4.1

Sponsor's protocol code number

hNSCALSII

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	FONDAZIONE CASA SOLLIEVO DELLA SOFFERENZA OPERA DI SAN PIO DA PIETRELCINA OSPEDALE IRCCS
B.1.3.4	Country	Italy
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	MInistero della Salute-PNRR
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fondazione IRCCS Casa Sollievo della Sofferenza
B.5.2	Functional name of contact point	Clinical Trial Office
B.5.3	Address:
B.5.3.1	Street Address	viale Cappuccini
B.5.3.2	Town/ city	San Giovanni Rotondo
B.5.3.3	Post code	71013
B.5.3.4	Country	Italy
B.5.4	Telephone number	0882410925
B.5.6	E-mail	clinicaltrialoffice@operapadrepio.it

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	hNSC
D.3.2	Product code	[hNSC]
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intracerebral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	hNSC
D.3.9.3	Other descriptive name	hNSC
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	50000
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.8.4	Route of administration of the placebo	Intracerebral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Amyotrophic Lateral Sclerosis (ALS)

Sclerosi Laterale Amiotrofica (SLA)

E.1.1.1

Medical condition in easily understood language

Amyotrophic Lateral Sclerosis (ALS)

Sclerosi Laterale Amiotrofica (SLA)

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

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

The primary trial outcome is safety, assessed with respect to the incidence of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) over the whole study period.

L’obiettivo primario dello studio è la sicurezza, misurata attraverso l’incidenza di Eventi Avversi legati al trattamento (TEAEs) e di Eventi Avversi Seri (SAEs) durante l’intero periodo dello studio.

E.2.2

Secondary objectives of the trial

The secondary aim is to measure the effects of the treatment on the progression of the disease

Scopo secondario è quello di misurare gli effetti del trattamento sulla progressione della malattia

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Patient provides written informed consent, informed consent signature collection prior to any study procedure (patient has good acceptance and understanding of the informed consent);
2.Definite, probable diagnosis according to the revised El Escorial criteria;
3.Age: 18-65 years;
4.FVC =70%;
5.Onset = 24 months;
6.Patients with an ALSFRS-R score of at least 26; overall, including a score of at least 2 on each of the 1-9 ALSFRS-R individual component items and of at least 3 of the 10-12 individual components items
7.Evidence of fast progression of the disease. We exclude slow progressors at the time of screening defined as Patient with an ALSFRS-R total score progression between onset of the disease and screening of =0.3 per month. We document the fast progression of the disease defined as ALSFRS-R total score decrease of = 1 point per month during a 12 week run-in period between screening and randomization;
8.Patient should be on a stable dose of Riluzole for > 30 days from pre-screening visit or not taking riluzole at all, nor plan to begin riluzole during the study period.
9.Patient is medically able to tolerate transient immunosuppression regimen;
10.Presence of a willing and able caregiver who understands the need to attend all follow-up visits, even if mobility declines

1. Il paziente deve fornire il consenso informato firmato, quindi l’ottenimento della firma del consenso informato deve avvenire prima di qualunque procedura prevista dallo studio (buona comprensione ed accettazione del consenso informato);
2. Diagnosi di SLA definita o probabile secondo i criteri rivisti di EI Escorial;
3. Età: 18-65 anni;
4. FVC = 70%;
5. Insorgenza = 24 mesi;
6. Paziente con un punteggio ALS-FRS-R di almeno 26 (con score non inferiore a 2 negli item ad 1 a 9 e non inferiore a 3 negli items da 10 a 12);
7. Documentata progressione rapida di malattia. Escludiamo i pazienti slow progressors al momento dello screening definito come Paziente con una progressione del punteggio totale ALSFRS-R tra l'insorgenza della malattia e lo screening di < 0,3 al mese. Documentiamo la rapida progressione della malattia definita come diminuzione del punteggio totale ALSFRS-R di = 1 punto al mese durante un periodo di run-in di 12 settimane tra lo screening e la randomizzazione;
8. Il paziente o deve assumere una dose stabile di Riluzolo per > 30 giorni prima del pre-screening, oppure non deve averlo assunto affatto né dev’essere
pianificato che lo inizi durante il periodo di studio;
9. Il paziente è clinicamente in grado di tollerare un regime di immunosoppressione transitorio;
10. Presenza di un tutore disponibile e capace che comprenda la necessità di presentarsi a tutte le visite di controllo, anche se la mobilità del paziente diminuisce.

E.4

Principal exclusion criteria

1. Psychiatric disease or other neurological diseases different from ALS;
2. Evidence of any concurrent illness or treatments limiting the safety to participate or any condition that the neurosurgeon feels may pose complications for the surgery;
3. Cancer within the previous 10 years;
4.Immunosuppressive therapy within 12 weeks of screening; active autoimmune disease or infection (including hepatitis B, hepatitis C, or HIV);
5.Cognitive impairment;
6.Contraindications to perform MRI scans, CSF withdrawal and Skin biopsy ;
7.Patient unable to understand informed consent form;
8.Pregnancy and breast feeding;
9.Patient has been treated previously with any stem cell or somatic cells therapy;
10.Patient has participated in another clinical treatment trial or received other experimental medications outside of a clinical trial within 1 month prior to start of this study.

1. Malattia psichiatrica o altre malattie neurologiche diverse dalla SLA;
2. Evidenza di eventuali malattie o trattamenti concomitanti che limitano la sicurezza del paziente a partecipare allo studio o qualsiasi altra condizione che, secondo il neurochirurgo, potrebbe rappresentare una complicanza per l’intervento;
3. Diagnosi di cancro nei 10 anni precedenti il reclutamento nello studio;
4. Terapia immunosoppressiva entro le 12 settimane dallo screening; malattia autoimmune attiva o un’infezione (incluse epatite B, epatite C o HIV)
5. Deterioramento cognitivo
6. Controindicazioni alla Risonanza Magnetica Nucleare (RMN), al prelievo di liquido cerebrospinale e alla biopsia cutanea;
7. Incapacità a comprendere il consenso informato;
8. Donne in gravidanza o in allattamento.
9. Paziente che è stato trattato precedentemente con altra terapia a base di cellule staminali o terapia somatica cellulare;
10. Paziente che ha partecipato ad un'altra sperimentazione clinica o ha ricevuto altri farmaci sperimentali al di fuori di una sperimentazione clinica 1 mese prima dell'inizio di questo studio.

E.5 End points

E.5.1

Primary end point(s)

safety (AEs incidence)

sicurezza (incidenza AE)

E.5.1.1

Timepoint(s) of evaluation of this end point

over the whole study period

durante la conduzione dello studio

E.5.2

Secondary end point(s)

To compare the change in slopes from the pre-transplantation period to the post transplantation period in FVC (=25% to =100% change for responders) between the treatment and placebo groups through 3 months post first transplantation.; To compare the slope of the rate of decline in the ALSFRS-R at 3 and 6 months following first transplantation relative to the 3-4 months baseline period before transplantation in all patients (both treatment and placebo groups); To compare the slope of the rate of decline in FVC at 3 and 6 months following first transplantation relative to the 3-4 months baseline period before transplantation in all patients (both treatment and placebo groups).; To collect data on the impact of hNSC transplantation on quality of life as measured by ALSAQ-40 scale.; compare the change in slopes in points per month (=0.5 to =2.5 for responders) from the pre-transplantation period to the post transplantation period in ALSFRS-R between the treatment and placebo groups through 3 months post first transplantation

Confrontare la variazione delle pendenze dal periodo pre-trapianto al periodo post-trapianto della FVC (variazione da =25% a =100% per i responder) tra i gruppi di trattamento e placebo attraverso 3 mesi dopo il primo trapianto.; • Confrontare la pendenza del tasso di declino dell'ALSFRS-R a 3 e 6 mesi dopo il primo trapianto rispetto al periodo basale di 3-4 mesi prima del trapianto in tutti i pazienti (sia il gruppo trattato che il gruppo placebo).; Confrontare la pendenza del tasso di declino della FVC a 3 e 6 mesi dopo il primo trapianto rispetto al periodo basale di 3-4 mesi prima del trapianto in tutti i pazienti (sia il gruppo trattato che il gruppo placebo).; Raccogliere dati sull'impatto del trapianto di cellule staminali neurali hNSC sulla qualità della vita misurata dalla scala ALSAQ-40.; Confrontare la variazione delle pendenze delle curve di progressione in punti al mese (da =0,5 a =2,5 per i responder) dal periodo pre-trapianto al periodo post-trapianto della scala ALSFRS-R tra il gruppo di trattamento e il gruppo placebo fino a 3 mesi dopo il primo trapianto.

E.5.2.1

Timepoint(s) of evaluation of this end point

through 3 months post first transplantation; 3 and 6 months following first transplantation; 3 and 6 months following first transplantation; during the conduct of the study; through 3 months post first transplantation

nei 3 mesi dopo il primo trapianto; 3 e 6 mesi post primo trapianto; 3 e 6 mesi post primo trapianto; durante la conduzione dello studio; nei 3 mesi dopo il primo trapianto

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

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

triplo cieco

triple blind

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

Information not present in EudraCT

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

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

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.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)

Long term Follow up

Contatti di Follow up a lungo termine

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

2023-05-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2024-05-31

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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