Clinical Trials Register

Summary
EudraCT Number:	2011-006156-37
Sponsor's Protocol Code Number:	FA_BBK_8
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:	2012-07-26
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

2011-006156-37

A.3

Full title of the trial

A double-blind, randomized, placebo-controlled, clinical trial to test the efficacy of Epoetin alfa on physical performance of Friedreich Ataxia patients.

Studio in doppio-cieco, randomizzato, controllato con placebo, per testare efficacia, sicurezza e tollerabilita' dell'Epoetina alfa su parametri funzionali nell'Atassia di Friedreich.

A.3.1

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

Erythropoieitn in Friedreich Ataxia

Eritropoietina nell'Atassia di Friedreich

A.3.2

Name or abbreviated title of the trial where available

FRIEMAX

A.4.1

Sponsor's protocol code number

FA_BBK_8

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01493973

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	UNIVERSITA' DEGLI STUDI DI NAPOLI FEDERICO II
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	FARA
B.4.2	Country	United States
B.4.1	Name of organisation providing support	AISA ONLUS
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	Universita' degli Studi di Napoli ''Federico II''
B.5.2	Functional name of contact point	Dipartimento di Scienze Neurologich
B.5.3	Address:
B.5.3.1	Street Address	Via Pansini, 5
B.5.3.2	Town/ city	Napoli
B.5.3.3	Post code	80131
B.5.3.4	Country	Italy
B.5.4	Telephone number	0817432671
B.5.5	Fax number	0815463663
B.5.6	E-mail	francesco.sacca@unina.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	Yes
D.2.1.1.1	Trade name	EPREX*1SIR 40000UI/ML 1ML
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN CILAG SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	80000
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)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
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	Yes
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	EPREX*1SIR 10000UI 1ML
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN CILAG SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	80000
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)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
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	Yes
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	BINOCRIT*1SIR 40000UI/1ML
D.2.1.1.2	Name of the Marketing Authorisation holder	SANDOZ SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	80000
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)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
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	Yes
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.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

FRIEDREICH ATAXIA

ATASSIA DI FRIEDREICH

E.1.1.1

Medical condition in easily understood language

FRIEDREICH ATAXIA

ATASSIA DI FREIDREICH

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10008025
E.1.2	Term	Cerebellar ataxia
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

efficacy of Epoetin alfa on exercise capacity in patients with Friedreich Ataxia

efficacia dell’Epoetina alfa sulla capacità fisica nei pazienti con Atassia di Friedreich

E.2.2

Secondary objectives of the trial

• Assess the efficacy of the study drug on frataxin levels • Assess the efficacy of the study drug on cardiomyopathy • Assess the efficacy of the study drug on vascular reactivity* • Assess the efficacy of the study drug on clinical progression • Assess the safety and tolerability of the study drug • Quality of life

•Determinare l’efficacia dell’EPO sui livelli di fratassina•Determinare l’efficacia dell’EPO sulla cardiopatia•Determinare l’efficacia dell’EPO sulla reattività vascolare*•Determinare l’efficacia dell’EPO sulla progressione di malattia•Determinare la sicurezza e tollerabilità dell’EPO•Effetto dell'EPO sulla qualità di vita

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

OTHER SUBSTUDIES:
Vascular reactivity

ALTRI SOTTOSTUDI:
Reattività vascolare

E.3

Principal inclusion criteria

• Molecular diagnosis of Friedreich Ataxia • Age ≥12 years • Body weight ≥30 Kg • SARA score ≤30 • Patient able to read and sign the informed consent

• Diagnosi molecolare di Atassia di Friedreich, con espansione GAA omozigote • Età ≥12 anni • Peso corporeo ≥30 Kg • SARA ≤30 • Pazienti in grado di comprendere il consenso informato

E.4

Principal exclusion criteria

• Treatment with Erythropoietin in the previous 12 months • Treatment with Idebenone • Contraindications to cardiopulmonary test: valvulopathies, ischemic cardiomyopathy, atrial fibrillation, asthma, chronic obstructive pulmonary disease, other arrhythmias judged as not compatible with exercise. • Any Cardiac and/or Hepatic and/or Renal disease judged as clinically significant by the investigator (any abnormal and clinically non significant cardiac disease associated with Friedreich Ataxia is not an exclusion criteria) • Any clinically significant ECG abnormalities that may interfere with the study • Any abnormal and clinically significant laboratory exams at screening visit that may interfere with the trial • Anemia with Hemoglobin <10 g/dL • Positive history for venous and/or arterial thrombosis • Drug-resistant arterial hypertension • Positive history for drug-resistant epilepsy • Patients in treatment with not allowed study drugs (starting from 1 month prior to screening) • Any acute/chronic disease that might interfere with the clinical trial, as judged by the investigator • Hypersensitivity to Epoetin alfa or any other component of the study drug • Patients not able to comply to the study • For female patients (Sexually not active, hysterectomized, sterilized, menopause patients are excluded from the following criteria): - Pregnancy, or - Breastfeeding, or - Inadequate contraception

• Trattamento con Eritropoietina nei 12 mesi precedenti • Trattamento con Idebenone • Controindicazioni al test cardiopolmonare: valvulopatie, cardiopatia ischemica, fibrillazione atriale, asma, BPCO, altre condizioni mediche giudicate incompatibili con il test. • Malattia cardiaca e/o epatica e/o renale giudicata come clinicamente significativa da parte dell’investigatore (qualunque anomalia cardiaca non clinicamente significativa associata all’atassia di Friedreich non rappresenta un criterio di esclusione) • Anomalie all’ECG che potrebbero interferire con lo studio • Alterazione nei parametri di laboratorio alla visita di screening che potrebbero interferire con lo studio • Anemia con emoglobina <10 g/dl • Storio clinica di trombosi arteriosa e/o venosa • Ipertensione farmaco resistente • Storia clinica di epilessia farmaco resistente • Pazienti in trattamento con farmaci non permessi (con effetto retrospettivo nei 30 giorni precedenti allo screening) • Malattia acuta o cronica che, a giudizio dello sperimentatore, potrebbe interferire con lo studio • Ipersensibilità all’eritropoietina o ai suoi eccipienti • Pazienti con compliance insufficiente • Per pazienti di sesso femminile (donne sessualmente non attive, isterectomizzate, sterilizzate, in menopausa, sono escluse dai successivi criteri): - gravidanza, o - allattamento, o - contraccezione inadeguata

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint is the peak oxygen consumption (VO2 max) at the cardiopulmonary exercise test (CPET)

Endpoint primario è il picco nel consumo di ossigeno (VO2 max) al test cadiopolmonare (CPET)

E.5.1.1

Timepoint(s) of evaluation of this end point

0, 24, and 48 weeks

0, 24, 48 settimane

E.5.2

Secondary end point(s)

• Secondary outcome variables at the CPET • Difference in frataxin levels in peripheral blood mononuclear cells (PBMCs), at all time points • Difference in the main Echocardiographic parameters at 6, and 12 months • Difference in vascular reactivity measured with FMD at 6, and 12 months* • Difference in the clinical scale SARA at 6, and 12 months • Analysis of serious and non-serious adverse events recorded during the clinical trial • EQ-5D/ADL/IADL • 9HPT

• Variabili secondarie alla CPET • Differenza nei liveli di fratassina nelle cellule mononucleate del sangue (PBMCs) • Differenza nei principali parametri ecocardiografici • Differenza nella reattività vascolare misurata con la FMD* • Differenza nella scala clinica SARA • Eventi seri e non-seri emersi durante la sperimentazione • EQ-5D/ADL/IADL • 9HPT

E.5.2.1

Timepoint(s) of evaluation of this end point

0, 12, 24, 36, and 48 weeks

0, 12, 24, 36, 48 settimane

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

Yes

E.6.7

Pharmacodynamic

Yes

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

Yes

E.8.1.5

Parallel group

Yes

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

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

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

final data analysis

Analisi finale dei dati

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

no program

Nessun programma

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

2012-07-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-05-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-12-16

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