Clinical Trials Register

Summary
EudraCT Number:	2016-000186-23
Sponsor's Protocol Code Number:	CICL670AIC04
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-02-09
Trial results	View 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

2016-000186-23

A.3

Full title of the trial

Open-label, multicenter, single arm, phase III study to collect additional safety and efficacy data with deferasirox film-coated tablets in patients completing study CICL670F2201.

Studio in aperto, multicentrico, a braccio singolo, di Fase III, per raccogliere dati di sicurezza d¿impiego e d¿efficacia supplementari con deferasirox in compresse rivestite con film in pazienti che completano lo studio CICL670F2201.

A.3.1

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

Safety and efficacy of deferasirox film-coated tablets in patients completing study CICL670F2201.

Sicurezza ed efficacia di deferasirox in compresse rivestite con film in pazienti che completano lo studio CICL670F2201.

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CICL670AIC04

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	NOVARTIS PHARMA SERVICES AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NOVARTIS FARMA S.P.A.
B.5.2	Functional name of contact point	Drug Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Largo Umberto Boccioni, 1
B.5.3.2	Town/ city	Origgio (VA)
B.5.3.3	Post code	21040
B.5.3.4	Country	Italy
B.5.4	Telephone number	00390296541
B.5.5	Fax number	0039029659066
B.5.6	E-mail	info.studiclinici@novartis.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	Yes
D.2.1.1.1	Trade name	Exjade
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	-
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEFERASIROX
D.3.9.1	CAS number	201530-41-8
D.3.9.2	Current sponsor code	ICL670
D.3.9.3	Other descriptive name	DEFERASIROX
D.3.9.4	EV Substance Code	SUB21981
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	90
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
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	No
D.IMP: 2
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	Yes
D.2.1.1.1	Trade name	Exjade
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	-
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEFERASIROX
D.3.9.1	CAS number	201530-41-8
D.3.9.2	Current sponsor code	ICL670
D.3.9.3	Other descriptive name	DEFERASIROX
D.3.9.4	EV Substance Code	SUB21981
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	180
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
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	No
D.IMP: 3
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	Yes
D.2.1.1.1	Trade name	Exjade
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	-
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEFERASIROX
D.3.9.1	CAS number	201530-41-8
D.3.9.2	Current sponsor code	ICL670
D.3.9.3	Other descriptive name	DEFERASIROX
D.3.9.4	EV Substance Code	SUB21981
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	360
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
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	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

Transfusion-dependent thalassemia or myelodysplastic syndrome at very low, low or intermediate (int-1) risk

Talassemia dipendente dalle trasfusioni o sindrome mielodisplastica (MDS) a rischio molto basso, basso o intermedio

E.1.1.1

Medical condition in easily understood language

Chronic iron overload due to transfusion-dependant anemias

Sovraccarico di ferro dovuto a trasfusioni di sangue

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

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	10054658
E.1.2	Term	Thalassemia
E.1.2	System Organ Class	100000004850

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10028534
E.1.2	Term	Myelodysplastic syndrome NOS
E.1.2	System Organ Class	100000004864

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

To evaluate the overall safety of deferasirox FCT formulation in patients with transfusion-dependent thalassemia or MDS at very low, low or intermediate risk

Valutare la sicurezza d¿impiego complessiva della formulazione FCT di deferasirox in pazienti con talassemia dipendente dalle trasfusioni o sindrome mielodisplastica a rischio molto basso, basso o intermedio.

E.2.2

Secondary objectives of the trial

To evaluate efficacy of deferasirox FCT on serum ferritin levels (decrease or maintenance, according to the individual therapeutic goal)

Valutare l'efficacia di deferasirox FCT sui livelli sierici di ferritina (diminuzione o mantenimento, in base all'obiettivo terapeutico individuale).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Have completed 24-weeks of study treatment as described in protocol (CICL670F2201).
• Are deemed to be tolerating deferasirox treatment by the investigator if continuing directly from protocol CICL670F2201.
• Provided written informed consent/assent before any study-specific procedures are performed. For pediatric patients, consent will be obtained from parent(s) or legal patient's representative. Investigators will also obtain assent of patients according to local, regional or national
guidelines. Additional inclusion criteria as per main body of the protocol may apply

- Completamento delle 24 settimane di trattamento in studio, come descritto nel protocollo (CICL670F2201).
- Lo sperimentatore ritiene che tollerino il trattamento con deferasirox.
- E’ stato fornito il consenso/assenso informato scritto ottenuto prima di qualsiasi procedura specifica per lo studio. Nei pazienti pediatrici il consenso sarà ottenuto dal/i genitore/i o dal rappresentate legale. Gli sperimentatori otterranno anche l’assenso del paziente in base alle linee-guida locali, regionali o nazionali.
- Lo sperimentatore ritiene che possano tollerare il trattamento con deferasirox continuando direttamente dal protocollo CICL670F2201.

E.4

Principal exclusion criteria

The exclusion criteria will follow those described for study CICl670F2201, which were as follows:
- Creatinine clearance below the contraindication limit in the locally approved prescribing information.
- Serum creatinine > 1.5 × upper limit of normal range (ULN) at Screening
- Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) > 5 × ULN,
- Significant proteinuria
Additional exclusion criteria may apply.

I pazienti eleggibili allo studio non devono presentare nessuno dei criteri di esclusione dello studio CICL670F2201, che sono riportati di seguito:
1. Clearance della creatinina inferiore al limite della controindicazione riportato nella scheda tecnica approvata localmente. La clearance della creatinina sarà valutata in base alla creatinina sierica alla Visita 1 di screening e alla Visita 2 di screening (il valore medio sarà utilizzato per i criteri di eleggibilità).
2. Creatinina sierica > 1,5 x ULN allo screening misurata alla Visita 1 di screening e alla Visita 2 di screening (il valore medio sarà utilizzato per i criteri di eleggibilità).
3. ALT (SGPT) > 5 x ULN a meno che la LIC confermi valori > 10 mg Fe/peso secco entro un periodo di 6 mesi prima della Visita 1 di screening.
4. Proteinuria significativa come indicato dal rapporto proteine urinarie/creatinina > 0,5 mg/mg in un campione di urine (non le prime urine del mattino) alla Visita 1 di screening o alla Visita 2 di screening.
5. Pazienti con compromissione significativa della funzionalità gastrointestinale (GI) o gastropatie che possono alterare significativamente l’assorbimento di deferasirox per via orale (ad es: colite ulcerosa, nausea non controllata, vomito, diarrea, sindrome da malassorbimento o resezione dell’intestino tenue).
6. Evidenza clinica o di laboratorio di epatite B o epatite C in fase attiva (HBsAg in assenza di HBsAb OPPURE HCV Ab positivo con HCV RNA positivo).
7. Pazienti con qualsiasi patologia psichiatrica o dipendenze che precludano la possibilità di fornire il proprio consenso informato o sottoporsi a qualsiasi opzione di trattamento o pazienti non disposti o che non possono aderire al protocollo.
8. Pazienti con un’anamnesi positiva di sieropositività HIV (Elisa o Western blot).
9. Anamnesi positiva per patologie neoplastiche a carico di qualsiasi sistema od organo trattate o non trattate, entro gli ultimi 5 anni, indipendentemente dall’evidenza di recidiva locale o metastasi, ad eccezione del carcinoma basocellulare cutaneo localizzato.
10. Pazienti partecipanti ad un altro studio clinico o in trattamento con un farmaco sperimentale.
11. Anamnesi positiva per ipersensibilità al farmaco in studio o agli eccipienti.
12. Condizioni mediche significative che potrebbero interferire con la capacità di partecipare a questo studio (ad es: ipertensione arteriosa sistemica non controllata, cardiopatia instabile non controllata dalla terapia medica standard, malattie sistemiche cardiovascolari, renali, epatiche, ecc.).
13. Donne potenzialmente fertili, definite come tutte le donne che fisiologicamente possono concepire, a meno che non utilizzino un metodo contraccettivo efficace durante la somministrazione del trattamento in studio.
Per gli ulteriori criteri di esclusione fare riferimento al protocollo.

E.5 End points

E.5.1

Primary end point(s)

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Numero dei partecipanti con eventi avversi come misurazione della sicurezza e della tollerabilità

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 24 months or 30 days from last dose.

Fino 24 mesi o 30 giorni dall'ultima dose.

E.5.2

Secondary end point(s)

Absolute and relative change of serum ferritin level overtime

Cambiamenti dei livelli di ferritina sierica

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline, up to 24 months or 7 days of last dose

Baseline, fino a 24 mesi o 7 giorni dall'ultima dose

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

Completion of this study as a whole will occur upon the availability and accuracy verification of the last data point (Visit 28) required for statistical analysis

Lo studio terminerà una volta verificata la disponibilità e la precisione dei dati raccolti alla vista 28 (last data point) necessari per l'analisi statistica.

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)

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)

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

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Paediatric patients aged = 10 years

Pazienti pediatrici con età = 10 anni

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)

After completion of the study, patients will revert to the use of ICL670 dispersible tablets if the FCT is not yet available locally

Dopo il completamento dello studio, se la formulazione in compresse rivestite con film di ICL670 non fosse ancora disponibile a livello locale, i pazienti ritorneranno all'uso di ICL670 nella formulazione di compresse dispersibili.

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

2016-08-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-06-07

P. End of Trial
P.	End of Trial Status	Completed

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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