Clinical Trials Register

Summary
EudraCT Number:	2011-001329-26
Sponsor's Protocol Code Number:	EPOSS2010
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:	2011-11-17
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

2011-001329-26

A.3

Full title of the trial

ErythroPOietin in ALS: a Study of dose-finding and Safety

Eritropoietina nella SLA: uno studio di identificazione della dose e sicurezza

A.3.1

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

Erythropoietin in Amyotrophic Lateral Sclerosis: a study to identify the best dose and the optimal route of administration and evaluate the safety

Eritropoietina nella Sclerosi Laterale Amiotrofica: uno studio per identificare la dose e la via di somministrazione ottiminali e valutarne la sicurezza

A.3.2

Name or abbreviated title of the trial where available

EPOSS2010

A.4.1

Sponsor's protocol code number

EPOSS2010

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	ISTITUTO NEUROLOGICO "CARLO BESTA"
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	ARISLA
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	Fondazione IRCCS Istituto Neurologico Carlo Besta
B.5.2	Functional name of contact point	Servizio Ricerca e Sviluppo Clinico
B.5.3	Address:
B.5.3.1	Street Address	Via Celoria, 11
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20133
B.5.3.4	Country	Italy
B.5.4	Telephone number	02/23942321
B.5.5	Fax number	02/23943569
B.5.6	E-mail	crc@istituto-besta.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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ERYTHROPOIETIN
D.3.9.1	CAS number	11096-26-7
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40000
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Amyotrophic Lateral Sclerosis

Sclerosi Laterale Amiotrofica

E.1.1.1

Medical condition in easily understood language

Degenerative motoneuron disease

Malattia degenerativa dei motoneuroni

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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10002026
E.1.2	Term	Amyotrophic lateral sclerosis
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

The project aims to assess: 1) safety and tolerability of rhEPO given at different doses and by different routes; 2) modulation of potential biomarkers involved in the neuroprotective activity of EPO; 3) percentage of rhEPO crossing the BBB in ALS patients. Since ALS patients are at risk for some events included in the primary outcome (e.g. venous thrombosis), a placebo arm will be included.

Il progetto mira a valutare: 1) la sicurezza e la tollerabilità di rhEPO somministrato a dosi diverse e per vie diverse, 2) modulazione dei biomarcatori potenzialmente coinvolte nell'attività neuroprotettivo di EPO, 3) la percentuale di rhEPO che attraversano la BBB nei pazienti con SLA. Poiché i pazienti SLA sono a rischio per alcuni eventi inclusi nel outcome primario (trombosi venosa), un braccio placebo saranno inclusi.

E.2.2

Secondary objectives of the trial

To assess safety and tolerability of rhEPO administered iv for 4 months or sc open in 60 patients with ALS. Patients will be treated fortnightly with 120,000, 80,000, or 40,000 IU / ml. Safety will be analyzed in relation to adverse events associated with the erythropoietic activity of rhEPO and compared to the placebo arm. Biomarkers will be investigated including EPCs, VEGF and rhEPO modulated by NO. It will assess the percentage of rhEPO through the BBB.

Valutare sicurezza e tollerabilità di rhEPO somministrata per 4 mesi i.v. o s.c. in aperto in 60 pazienti affetti da SLA. I pazienti saranno trattati quindicinalmente con 120.000, 80.000, o 40.000 Ul/ml. La sicurezza sarà analizzata in relazione agli eventi avversi connessi con l'attività eritropoietica di rhEPO e rispetto al braccio placebo. Saranno indagati biomarcatori tra cui EPC, VEGF e NO modulati da rhEPO. Si valuterà la percentuale di rhEPO che attraversa la BBB.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

STUDY POPULATION: 60 patients with diagnosis of laboratory-supported probable, probable, or definite ALS according to El Escorial revised criteria. PATIENTE ELIGIBILITY: 1. age 18-75 years 2. diagnosis of sporadic or familial ALS 3. onset of weakness <=36 months prior enrolment 4. willingness to undergo active contraception (excluding estroprogestinic drugs) for fertile female subjects throughout the entire study period 5. written informed consent. All patients will be required to take riluzole 100 mg daily and patients will be considered eligible if on stable dose for at least 60 days. Not following riluzole for any reason (e.g.side effects,etc.) will not be considered an exclusion criteria. Patients on riluzole at the randomization will be asked to remain on stable dose for the whole study. Patients not on riluzole will not take it for the entire study period

Popolazione in studio: 60 pazienti con diagnosi di SLA probabile, probabile supportata da laboratorio o definita secondo i criteri di El Escorial rivisti. CRITERI DI ELEGGIBILITA: 1. età 18-75 anni 2. diagnosi di SLA sporadica o familiare 3. insorgenza <= 36 mesi 4. volontà di sottoporsi a contraccezione attivi (esclusi farmaci estroprogestinic) per i soggetti di sesso femminile fertile per tutto il periodo di studi 5. consenso informato scritto. A tutti i pazienti sarà richiesto di assumere riluzolo 100 mg/die. La non assunzione per qualsiasi motivo (es effetti collaterali) non sarà considerato criterio di esclusione.

E.4

Principal exclusion criteria

EXCLUSION CRITERIA: 1. hematocrit >49% in men and >47% in women, hemoglobin value >15 g/dl in men and >13 g/dl in women 2. tracheotomy 3. clinical diagnosis of frontotemporal dementia, Parkinson or Alzheimer disease 5. history and/or instrumental evidence of previous myocardial infarction or thrombotic vascular events (such as stroke, transient ischemic attack, pulmonary emboli, retinal thrombosis, deep vein or arterial thrombosis including asymptomatic carotid and/or vertebral stenosis >30%) 6. clinically evident cardiac disease (ischemic heart disease, congestive heart failure, arrhythmia) 7. uncontrolled hypertension (systolic blood pressure >160 mmHg and diastolic blood pressure >95 mmHg irrespective of anti-hypertensive treatments at two consecutive evaluations) 8. active malignancy, polycythemia, myeloproliferative disorders 9. hypercoagulable disorders (ref. Deitcher S, in Current Clinical Medicine 2009, Cleveland Clinic ed., Elsevier) 10. porphyria 11. known hypersensitivity to human albumin 12. female subjects pregnant or lactating 13. use of post-menopausal drugs (estrogen, progestinic, or their combination) 14. use of hormonal contraception drugs 15. use of experimental drug or participation in a clinical trial within 3 months prior to screening 16. previous treatment with hematopoietic stem cells

Criteri di esclusione: 1. ematocrito> 49% negli uomini e> 47% nelle donne, il valore di emoglobina> 15 g / dl negli uomini e> 13 g / dl nelle donne 2. tracheotomia 3. diagnosi clinica di demenza frontotemporale, il Parkinson o la malattia di Alzheimer 5. storia e / o evidenze strumentali di precedente infarto miocardico o eventi trombotici vascolari (come ictus, attacco ischemico transitorio, embolia polmonare, trombosi retinica, trombosi venosa profonda o arteriosa compresa carotidea asintomatica e / o stenosi vertebrale> 30%) 6. clinicamente evidente malattia cardiaca (cardiopatia ischemica, scompenso cardiaco congestizio, aritmie) 7. ipertensione non controllata (pressione sistolica> 160 mmHg e pressione diastolica> 95 mmHg a prescindere dal trattamento antipertensivo a due valutazioni consecutive) 8. tumore maligno in atto, policitemia, malattie mieloproliferative 9. Disturbi di ipercoagulabilità (rif. Deitcher S, in corrente Medicina Clinica 2009, Cleveland Clinic ed., Elsevier) 10. porfiria 11. ipersensibilità nota alla albumina umana 12. soggetti di sesso femminile in gravidanza o allattamento 13. uso di farmaci post-menopausa (estrogeni, progestinici, o loro combinazione) 14. uso di farmaci contraccettivi ormonali 15. uso del farmaco sperimentale o la partecipazione ad un trial clinico nei 3 mesi precedenti allo screening 16. precedente trattamento con cellule staminali ematopoietiche

E.5 End points

E.5.1

Primary end point(s)

Discontinuation of treatment because of hematocrit or haemoglobin values, adverse events, or death

L'interruzione del trattamento a causa di valori di ematocrito o emoglobina, gli eventi avversi, o morte

E.5.1.1

Timepoint(s) of evaluation of this end point

4 months

4 mesi

E.5.2

Secondary end point(s)

Changes in biomarkers analyzed between treatment groups

Variazioni dei biomarkers analizzati tra gruppi di trattamento

E.5.2.1

Timepoint(s) of evaluation of this end point

4 months

4 mesi

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

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)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

- Stesso farmaco ad altro dosaggio

- same IMP used at different dosage

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

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

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)

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

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)

CLINICAL FOLLOW-UP PLANNED PROGRAM (FIRST VISIT TO 1 MONTH AFTER THE END OF THE STUDY, AFTER EVERY 3 MONTHS)

PROSECUZIONE DEI CONTROLLLI CLINICI DI FOLLOW-UP CON PROGRAMMAZIONE PIANIFICATA (PRIMA VISITA 1 MESE DOPO IL TERMINE DELLO STUDIO, SUCCESSIVE OGNI 3 MESI)

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

2011-08-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-06-08

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

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