Clinical Trials Register

Summary
EudraCT Number:	2021-000700-38
Sponsor's Protocol Code Number:	TEM-LT
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:	2021-06-07
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

2021-000700-38

A.3

Full title of the trial

A follow-up study evaluating the long term safety of autologous CD34+-enriched hematopoietic progenitor cells genetically modified with a lentiviral vector encoding for the human interferon-a2 gene previously administered to patients with glioblastoma multiforme

Studio di follow-up atto a valutare la sicurezza a lungo termine delle cellule progenitrici ematopoietiche autologhe CD34+ geneticamente modificate con un vettore lentivirale codificante per il gene umano dell'interferone-a2 precedentemente somministrate in pazienti affetti da glioblastoma multiforme

A.3.1

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

A long-term monitoring study of patients suffering from a malignant neoplasm of the central nervous system previously treated with hematopoietic stem cells

Studio di monitoraggio a lungo termine di pazienti affetti da un tumore maligno del sistema nervoso centrale trattati precedentemente con cellule staminali ematopoietiche

A.3.2

Name or abbreviated title of the trial where available

TEM-LT

A.4.1

Sponsor's protocol code number

TEM-LT

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	GENENTA SCIENCE SRL
B.1.3.4	Country	Italy
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	Genenta Science S.r.l.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Genenta Science
B.5.2	Functional name of contact point	Sportello Informazioni Sperimentazi
B.5.3	Address:
B.5.3.1	Street Address	Via Olgettina 58
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20132
B.5.3.4	Country	Italy
B.5.4	Telephone number	0226435125
B.5.5	Fax number	0226434621
B.5.6	E-mail	info-trial@genenta.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	NA
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Bath additive
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Auricular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	99999
D.3.10	Strength
D.3.10.1	Concentration unit	% (V/V) percent volume/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	999999
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)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	NON viene impiegato nessun IMP

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

Glioblastoma multiforme (GBM)

E.1.1.1

Medical condition in easily understood language

Malignant brain tumor

Tumore maligno al cervello

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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	10018337
E.1.2	Term	Glioblastoma multiforme
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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	10018337
E.1.2	Term	Glioblastoma multiforme
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 objective is to evaluate the long term mutagenic safety of Temferon as determined by the incidence of second malignancies and specifically hematopoietic malignancies.

L'obiettivo primario è valutare la sicurezza mutagenica a lungo termine di Temferon determinata dall'incidenza di tumori secondari e specificatamente di tumori ematologici.

E.2.2

Secondary objectives of the trial

The secondary objectives are:
• To assess the long term mutagenic potential of Temferon as determined by the incidence of insertional mutagenic events in peripheral white blood cells;
• To assess the general long-term safety of Temferon as determined by the incidence of drug reactions attributed to Temferon;
• To assess the presence in the long term of transduced myeloid cells in the peripheral blood;
• To assess disease progression and survival in patients who have received Temferon.

Gli obiettivi secondari sono:
• Valutare il rischio di mutazioni a lungo termine associato a Temferon e determinato dalla potenziale presenza di eventi inserzionali mutageni nei globuli bianchi del sangue periferico;
• Valutare la sicurezza generale a lungo termine di Temferon determinata dall'incidenza delle reazioni al farmaco attribuite a Temferon;
• Valutare la presenza a lungo termine di cellule mieloidi trasdotte nel sangue periferico;
• Valutare la progressione di malattia e la sopravvivenza nei pazienti che hanno ricevuto Temferon.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion Criteria at Entry:
• Patients who have received Temferon and completed 2 years follow-up in the TEM-GBM study.
• Able and willing to provide written informed consent and comply with the study protocol and procedures.

Criteri di Inclusione all’Ingresso:
• I pazienti devono aver ricevuto Temferon e completato il follow-up di 2 anni previsto per lo studio TEM-GBM.
• I pazienti devono essere in grado e disponibili a fornire un consenso informato scritto, a rispettare il protocollo e le procedure dello studio.

E.4

Principal exclusion criteria

There are no exclusion criteria for this study.

Non sono previsti criteri di esclusione per questo studio.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is to assess the mutagenic potential of Temferon over 8 years following administration (the first two years of the monitoring are included in the TEM-GBM_001 study), as evaluated by the incidence of hematopoietic malignancies or potentially life threatening, malignant solid or other hematological tumors.

L’endpoint primario è valutare il potenziale rischio mutageno di Temferon negli 8 anni successivi alla sua somministrazione (i primi due anni di rilevazione sono compresi nello studio TEM-GBM_001), valutato sulla base dell’incidenza di tumori maligni ematopoietici o tumori maligni solidi o altri tumori ematologici che possono essere potenzialmente una minaccia per la vita del paziente.

E.5.1.1

Timepoint(s) of evaluation of this end point

Over 8 years following Temferon administration (the first two years of the monitoring are included in the TEM-GBM_001 study).

Negli 8 anni successivi alla somministrazione di Temferon (i primi due anni di rilevazione sono compresi nello studio TEM-GBM_001).

E.5.2

Secondary end point(s)

Safety
• The incidence of increasingly expanding clone of peripheral white blood cells with evidence of vector genome insertion within or in close proximity to a putative cancer associated gene
• Long-term tolerability and safety of Temferon up to 8 years following Temferon administration, evaluated by:
o Routine clinical and laboratory surveillance;
o Development or exacerbation of non-GBM related neurologic disorders attributed to Temferon exposure;
o Development or exacerbation of hematologic disorders attributed to Temferon exposure;
o Development or exacerbation of rheumatologic disorders attributed to Temferon exposure;
o Development or exacerbation of autoimmune manifestations attributed to Temferon exposure;
o Development of infections that are attributed to Temferon exposure;
Efficacy
• Identify the persistence or progressive exhaustion of transduced myeloid cells in peripheral blood (PB) between Year 2 and Year 8 as determined by VCN>0.01.
• Determine the proportions of patients achieving complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) annually between Year 2 and Year 8 visits using standard iRANO criteria.
• Overall Survival (OS) up to 8 years, will be calculated from the first day following Temferon administration.

Sicurezza
• Verificarsi dell’espansione di cloni di globuli bianchi del sangue periferico con evidenza di inserzione del genoma virale del genoma all’interno o in stretta prossimità di un gene putativo associato al tumore;
• Tollerabilità e sicurezza a lungo termine del Temferon fino a 8 anni dopo la somministrazione dello stesso, valutate attraverso:
o Il monitoraggio clinico ed esami standard di laboratorio;
o Lo sviluppo o l’esacerbazione di disturbi neurologici non correlati al GBM attribuiti all'esposizione a Temferon;
o Lo sviluppo o l’esacerbazione di disturbi ematologici attribuiti all'esposizione a Temferon;
o Lo sviluppo o l’esacerbazione di disturbi reumatologici attribuiti all'esposizione a Temferon;
o Lo sviluppo o l’esacerbazione di manifestazioni autoimmuni attribuite all'esposizione a Temferon;
o Lo sviluppo di infezioni attribuite all'esposizione a Temferon;
Efficacia
• Identificare la persistenza o il progressivo esaurimento delle cellule mieloidi trasdotte nel sangue periferico (PB) tra l'anno 2 e l'anno 8 dalla somministrazione di Temferon, determinati da VCN > 0,01.
• Valutare annualmente la percentuale di pazienti che ottiene una risposta completa (CR), una risposta parziale (PR), malattia stabile (SD) e progressione di malattia (PD) tra l’anno 2 e l’anno 8 dalla somministrazione di Temferon, utilizzando i criteri standard iRANO.
• Calcolare la sopravvivenza globale (OS) fino a 8 anni, partendo dal primo giorno successivo alla somministrazione di Temferon.

E.5.2.1

Timepoint(s) of evaluation of this end point

Over 8 years following Temferon administration.

Negli 8 anni successivi alla somministrazione di Temferon.

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

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

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)

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

Yes

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)

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

2021-07-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-09

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

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