Clinical Trials Register

Summary
EudraCT Number:	2018-001029-14
Sponsor's Protocol Code Number:	P150949J
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-03-07
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

2018-001029-14

A.3

Full title of the trial

A phase I/II Study evaluating the safety and the efficacy of Human T Lymphoid Progenitor (HTLP) injection to accelerate immune reconstitution after partially HLA compatible allogeneic hematopoietic stem cell transplantation in SCID patients

Studio di fase I/II che valuta la sicurezza e l'efficacia dell'infusione di progenitori linfoidi umani T (HTLP) per accelerare la ricostituzione immunitaria dopo il trapianto di cellule staminali ematopoietiche allogeniche parzialmente HLA compatibili in pazienti con Deficit Immunitario Combinato Severo ( SCID)

A.3.1

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

HTLP

A.3.2

Name or abbreviated title of the trial where available

HTLP NECKER

HTLP Necker

A.4.1

Sponsor's protocol code number

P150949J

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	ASSITANCE PUBLIQUE DES HOPITAUX DE PARIS
B.1.3.4	Country	France
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	DGOS
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
B.5.2	Functional name of contact point	DRCI Hôpital St Louis
B.5.3	Address:
B.5.3.1	Street Address	1 av. Claude Vellefaux
B.5.3.2	Town/ city	PARIS
B.5.3.3	Post code	75010
B.5.3.4	Country	France
B.5.6	E-mail	coralie.villeret@aphp.fr

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	HTLP
D.3.2	Product code	[HTLP]
D.3.4	Pharmaceutical form	Concentrate for solution for injection/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.3.9.2	Current sponsor code	P150949J
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

SCID pediatric patients (n=12 for analysis) requiring an HLA partially compatible allogeneic HSCT.

Pazienti pediatrici SCID (n=12 per l'analisi) che richiedono un HSCT allogenico parzialmente compatibile.

E.1.1.1

Medical condition in easily understood language

severe combined immunodeficiency

immunodeficienza grave e combinata

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10010099
E.1.2	Term	Combined immunodeficiency
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic 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

The main objective is to assess the procedure's efficacy and safety:

1. (= 300/µL total CD3+ TCRaß+ T cells at 3 months)
2. • Dose-limiting toxicity (DLT), including graft versus host disease (GvHD) grade III-IV and Immune reconstitution inflammatory syndrome (IRIS)

Valutare la sicurezza e l'efficacia della procedura.
La valutazione del obbietivo primario sarà realizzata con endpoint co-primari misurati a 3 mesi:
• Efficacia (= 300/µL di cellule T CD3+ TCRaß+ totali).
• Dose-limiting toxicity (DLT), compresa la malattia da trapianto contro l'ospite (GvHD) di grado III-IV e la sindrome infiammatoria da ricostituzione immunitaria (IRIS).

E.2.2

Secondary objectives of the trial

" Time course of reconstitution of the different T cell subpopulations (numbers, functions and repertoires), thymic output and diversity of the T cell receptor repertoire by immunophenotyping, proliferation assays in the presence of mitogens and antigens, TCR repertoire analysis and TRECs values. A complete immunological assessment will be performed at 3, 6, 12 and 24 months and as soon as the number of CD3+ TCR aß cells in the blood reaches > 300/µl with particular attention to the time necessary to reach a normal number of naïve CD4 and CD8 T cells for the patient according to age
" Cumulative incidence of opportunistic infections at 3, 6 and 12 months
" Cumulative incidence of acute and chronic episodes of GVHD and their grade (at 3, 6, 12 and 24 months post-transplantation) according to Glucksgber GVHD staging
" Overall survival at 2 years and EFS

• Tempo necessario alla ricostituzione delle diverse sottopopolazioni di cellule T (numero, fenotipo e repertorio), la riposta proliferativa delle cellule T ai mitogeni e antigeni, analisi del repertorio TCR e valori dei recent thymic emigrants (TRECs). La valutazione immunologica completa sarà eseguita a 3, 6, 12 e 24 mesi e quando il numero di cellule CD3+ TCRaß+ nel sangue raggiunge >300/µL con particolare attenzione al tempo necessario per raggiungere un numero normale di cellule T aß CD4 e CD8 naïve per il paziente secondo l'età.
• Incidenza cumulativa di infezioni opportunistiche a 3, 6 e 12 mesi.
• Incidenza cumulativa di episodi di GvHD acuta e cronica e loro grado (a 3, 6, 12 e 24 mesi dopo il trapianto) secondo la stadiazione GvHD di Glucksgberg.
• Sopravvivenza globale (OS) e sopravvivenza priva di eventi (EFS) a 2 anni.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Pediatric patients affected by any type of SCID confirmed by clinical, immunological and/or molecular diagnosis and eligible for an allogeneic HSCT
• Absence of a matched sibling donor or a matched unrelated donor (MUD) 10/10
• Clinical conditions incompatible with the search of a MUD
• Written, informed consent of parents/ legal representative (child)
• Age = 2 years at the time of screening
• No prior therapy with allogeneic stem cell transplantation
• No treatment with another investigational drug within one month before inclusion
• Patient affiliated to social security

• Pazienti pediatrici affetti da qualsiasi tipo di SCID confermato dalla diagnosi clinica, immunologica e/o molecolare e idonei per un HSCT allogenico.
• Assenza di un donatore familiare HLA-compatibile o di un donatore volontario HLA-compatibile (MUD) 10/10.
• Condizioni cliniche incompatibili con la ricerca di un MUD.
• Consenso scritto e informato dei genitori/rappresentante legale.
• Età = 2 anni allo screening.
• Assenza di terapia con trapianto di cellule staminali allogeniche precedente.
• Nessun trattamento con un altro farmaco sperimentale entro un mese prima dell'inclusione.
• Paziente affiliato al sistema di assicurazione sanitaria nazionale quando applicabile e in conformità con la raccomandazione delle leggi nazionali in vigore relative alla ricerca biomedicale.

E.4

Principal exclusion criteria

" Presence of an HLA genoidentical donor
" Absence of written parental consent
" Treatment with another investigational drug within one month before inclusion
" Positive for HIV infection by genome PCR
" Contra-indication to allogeneic transplantation or conditioning therapy (except SCID patients with DNA repair deficiency)

• Presenza di un donatore HLA genoidentico.
• Assenza di consenso informato firmato dei genitori rappresentante legale.
• Trattamento con un altro farmaco in sperimentazione entro un mese prima dell'inclusione.
• Positivo all'infezione da HIV (tra PCR del genoma).
• Controindicazione al trapianto allogenico o alla terapia di condizionamento (eccetto pazienti SCID con deficit di riparazione del DNA).

E.5 End points

E.5.1

Primary end point(s)

_ Efficacy (= 300/µL total CD3+ TCRaß+ T cells)
_ Dose limiting toxicity (DLT), including graft versus host disease (GvHD) grade III/IV and Immune reconstitution inflammatory syndrome (IRIS)

• Efficacia (= 300/µL di cellule T CD3+ TCRaß+ totali).
• Dose-limiting toxicity (DLT), compresa la malattia da trapianto contro l'ospite (GvHD) di grado III-IV e la sindrome infiammatoria da ricostituzione immunitaria (IRIS).

E.5.1.1

Timepoint(s) of evaluation of this end point

coprimary endpoints measured at 3 months

endpoint co-primari misurati a 3 mesi

E.5.2

Secondary end point(s)

• Time course of reconstitution of the different T cell subpopulations (numbers, functions and repertoires), thymic output and diversity of the T cell receptor repertoire by immunophenotyping, proliferation assays in the presence of mitogens and antigens, TCR repertoire analysis and TRECs values. A complete immunological assessment will be performed at 3, 6, 12 and 24 months and as soon as the number of CD3+ TCRaß+ cells in the blood reaches >300/µL with particular attention to the time necessary to reach a normal number of naïve CD4 and CD8 aß T cells for the patient according to age.
• _Cumulative incidence of opportunistic infections at 3, 6 and 12 months
• _Cumulative incidence of acute and chronic episodes of GvHD and their grade (at 3, 6, 12 and 24 months posttransplantation) according to Glucksgberg GvHD staging
• _ Overall survival at 2 years and EFS

E.5.2.1

Timepoint(s) of evaluation of this end point

-A complete immunological assessment will be performed at 3, 6, 12 and 24 months and as soon as the number of CD3+ TCRaß+ cells in the blood reaches >300/µL with particular attention to the time necessary to reach a normal number of naïve CD4 and CD8 aß T cells for the patient according to age.
-Cumulative incidence of opportunistic infections at 3, 6 and 12 months
-Cumulative incidence of acute and chronic episodes of GvHD and their grade (at 3, 6, 12 and 24 months posttransplantation) according to Glucksgberg GvHD staging
-Overall survival at 2 years and EFS

La valutazione immunologica completa sarà eseguita a 3, 6, 12 e 24 mesi e quando il numero di cellule CD3+ TCRaß+ nel sangue raggiunge >300/µL con particolare attenzione al tempo necessario per raggiungere un numero normale di cellule T aß CD4 e CD8 naïve per il paziente secondo l'età.
• Incidenza cumulativa di infezioni opportunistiche a 3, 6 e 12 mesi.
• Incidenza cumulativa di episodi di GvHD acuta e cronica e loro grado (a 3, 6, 12 e 24 mesi dopo il trapianto) secondo la stadiazione GvHD di Glucksgberg.
• Sopravvivenza globale (OS) e sopravvivenza priva di eventi (EFS) a 2 anni.

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

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)

Yes

E.7.1.1

First administration to humans

Yes

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

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.8.2.4

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.8.4.1

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

Information not present in EudraCT

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

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

Yes

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)

Yes

F.1.1.3.1

Number of subjects for this age range:

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

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)

F.1.2

Adults (18-64 years)

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)

none

nessuna

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

2022-09-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-02-02

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

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