Clinical Trials Register

Summary
EudraCT Number:	2014-001427-79
Sponsor's Protocol Code Number:	TIRCON2012V1-EXT
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:	2021-06-04
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

2014-001427-79

A.3

Full title of the trial

Long-term Safety and Efficacy Study of Deferiprone in Patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN)

A.3.1

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

An 18-month extension of an international trial of deferiprone in patients with iron storage brain disorders

A.3.2

Name or abbreviated title of the trial where available

Long-term safety and efficacy study of deferiprone in patients with pantothenate kinase-associated n

Studio a lungo termine sulla sicurezza ed efficacia di deferiprone in pazienti con neurodegenerazion

A.4.1

Sponsor's protocol code number

TIRCON2012V1-EXT

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02174848

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	APOTEX EUROPE B.V.
B.1.3.4	Country	Netherlands
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	ApoPharma Inc.
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ApoPharma Inc.
B.5.2	Functional name of contact point	John Connelly
B.5.3	Address:
B.5.3.1	Street Address	200 Barmac Drive
B.5.3.2	Town/ city	Toronto
B.5.3.3	Post code	M9L 2Z7
B.5.3.4	Country	Canada
B.5.4	Telephone number	14164017296
B.5.5	Fax number	14164013869
B.5.6	E-mail	jconnell@apopharma.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	deferiprone 80 mg/mL oral solution
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	Yes
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	DEFERIPRONE
D.3.9.1	CAS number	30652-11-0
D.3.9.2	Current sponsor code	APO-066
D.3.9.3	Other descriptive name	DEFERIPRONE
D.3.9.4	EV Substance Code	SUB06941MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
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	Yes
D.3.11.13.1	Other medicinal product type	Iron chelating Agent

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

Pantothenate Kinase-Associated Neurodegeneration (PKAN)

Pazienti con neurodegenerazione associata a pantotenato chinasi (PKAN)

E.1.1.1

Medical condition in easily understood language

Pantothenate Kinase-Associated Neurodegeneration (PKAN). Patients with PKAN have high levels of iron in certain brain regions, and this extra iron acts to damage brain cells and may be the cause of th

Pazienti con neurodegenerazione associata a pantotenato chinasi (PKAN). I pazienti con PKAN presentano elevati livelli di ferro in determinate regioni cerebrali, e questo accumulo di ferro danneggia l

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10053643
E.1.2	Term	Neurodegenerative disorder
E.1.2	System Organ Class	10029205 - Nervous system disorders

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 long-term safety and tolerability of deferiprone in patients with PKAN.

Valutare la sicurezza e la tollerabilità a lungo termine di deferiprone in pazienti con PKAN.

E.2.2

Secondary objectives of the trial

• To evaluate the change in severity of dystonia over time in patients with PKAN treated with deferiprone.
• To evaluate global improvement over time in patients with PKAN treated with deferiprone.

• Valutare la variazione nella gravità della distonia nel tempo in pazienti con PKAN trattati con deferiprone.
• Valutare il miglioramento globale nel tempo in in pazienti con PKAN trattati con deferiprone.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Completed study TIRCON2012V1

2. Sexually active females of childbearing potential, including those who are peri-menopausal (defined as less than 2 years since last menstrual period) must have a negative pregnancy test result at Visit 1 (if applicable; in cases where the investigator determines there is no reasonable risk of pregnancy because of significant incapacity, pregnancy testing will not be performed). In addition, if applicable, they must meet at least one of the following criteria: Use an effective method of contraception during the study and within 30 days following their last dose of study medication, OR; Participate in a non-heterosexual lifestyle, OR; Have a male sexual partner who has been sterilized (supporting evidence required).

Approved methods of contraception will consist of the following or must follow local requirements: Oral contraceptive used in conjunction with condom, diaphragm, or spermicide; Hormonal implant used in conjunction with condom, diaphragm, or spermicide; Injectable contraceptive used in conjunction with condom, diaphragm, or spermicide; Diaphragm or condom used with spermicide.

If a hormonal contraception is used, it should have a Pearl index <1%.

Female patients who meet any of the following criteria are not of childbearing potential and therefore do not need to practice contraception: Post-menopausal (last menstrual period > 2 years ago); Had a tubal ligation (supporting evidence required); Had a hysterectomy or oophorectomy (supporting evidence required).

3. Fertile heterosexual males and/or their partners must agree to use an effective method of contraception during the study and for 30 days following the last dose of study medication.

4. Patients and/or their authorized legal representatives must provide signed and dated written informed consent prior to the first study intervention, and patients must be able to adhere to study restrictions, appointments, and evaluation schedules. Patients who are minors must sign an assent form as per local regulatory requirements.

E.4

Principal exclusion criteria

1. Withdrew from the study TIRCON2012V1 for reasons of safety.

2. Plan to participate in another clinical trial at any time from the day of enrolment until 30 days post-treatment in the current study.

3. Presence of any medical, psychological, or psychiatric condition which in the opinion of the investigator would cause participation in the study to be unwise.

4. Pregnant, breastfeeding, or planning to become pregnant during the study period.

E.5 End points

E.5.1

Primary end point(s)

• Adverse events (AEs): Frequency, severity, time to onset, duration, and relatedness to study product
• Serious adverse events (SAEs): Frequency, severity, time to onset, duration, and relatedness to study product
• Number of discontinuations due to AEs

• Eventi avversi (AE): Frequenza, gravità, tempo all'insorgenza, durata e correlazione al prodotto in studio
• Eventi avversi seri (SAE): Frequenza, gravità, tempo all'insorgenza, durata e correlazione al prodotto in studio
• Numero di sospensioni a causa degli AE

E.5.1.1

Timepoint(s) of evaluation of this end point

18 months

18 mesi

E.5.2

Secondary end point(s)

• Change in the Barry-Albright Dystonia Scale (BAD) total score from baseline (defined as prior to the start of deferiprone therapy) to Visit 4, as assessed by central evaluation of videotapes; Proportion of patients with improved or unchanged BAD scale total score between baseline and Visit 4 (responder analysis); • Change from baseline to Visit 4 in BAD scale score per body region (eyes, mouth, neck, trunk, and each upper and lower extremity), as assessed by central evaluation of videotapes; Change in score on the Patient Global Impression of Improvement (PGI-I) from Visit 1 to Visit 4; Proportion of patients showing an improvement on PGI-I at Visit 4 (responder analysis)

• Variazione nel punteggio totale della scala Barry-Albright Dystonia Scale (BAD) dal basale (definito come valore anteriore all'avvio della terapia con deferiprone) alla Visita 4, come valutata mediante valutazione centrale di videocassette; Percentuale di pazienti con punteggio totale della scala BAD migliorato o invariato tra il basale e la Visita 4 (analisi dei responder); • Variazione dal basale alla Visita 4 nel punteggio della scala BAD per regione del corpo (occhi, bocca, collo, tronco e ciascun arto superiore e inferiore), come valutata mediante valutazione centrale di videocassette; Variazione nel punteggio della scala Patient Global Impression of Improvement (PGI-I) dalla Visita 1 alla Visita 4; Percentuale di pazienti che mostrano un miglioramento del punteggio della scala PGI-I alla Visita 4 (analisi dei responder)

E.5.2.1

Timepoint(s) of evaluation of this end point

Visits 1, 2, 3, 4; Visits 1, 2, 3, 4; Visits 1, 2, 3, 4; Visits 1, 2, 3, 4; Visit 4

Visita 1, 2, 3, 4; Visita 1, 2, 3, 4; Visita 1, 2, 3, 4; Visita 1, 2, 3, 4; Visita 4

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

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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.8.3

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

Germany

Italy

United Kingdom

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

The last patient last visit is estimated for April 2018. This will be followed by analysis and interpretation of the results.

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)

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)

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

Children > 4 years
Adults with legal representative

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)

If the preliminary evidence indicates that deferiprone is safe and effective for this indication, the drug will be made available as compassionate use until we get approval for the drug. The investigators will have to request for the compassionate use. If the approval is not granted, the investigators will cancel the compassionate use.

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

2015-07-31

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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