Clinical Trials Register

Summary
EudraCT Number:	2006-006482-16
Sponsor's Protocol Code Number:	EPO2006-AISSM04
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:	2007-05-15
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

2006-006482-16

A.3

Full title of the trial

COMPARISON BETWEEN EPOYETIN ALONE ET EPOYETIN ASSOCIATED TO DIFFERENTIATING TERAPY WITH ACID 13-CIS-RETINOICO AND VITAMIN D3 DIIDROXILATED IN MYELODISPLASTIC SYNDROMES WITHOUT BLASTS EXCESS.

CONFRONTO TRA ERITROPOIETINA DA SOLA ED ERITROPOIETINA ASSOCIATA A TERAPIA DIFFERENZIANTE CON ACIDO 13-CIS-RETINOICO E VITAMINA D3 DIIDROSSILATA NELLE SINDROMI MIELODISPLASTICHE SENZA ECCESSO DI BLASTI.

A.3.2

Name or abbreviated title of the trial where available

EPO2006-AISSM04

A.4.1

Sponsor's protocol code number

EPO2006-AISSM04

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	FISM ONLUS
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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*IV FL 4000UI 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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Erythropoietin
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
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	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 Applicabile
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	DIBASE*OS GTT 10ML 10000UI/ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ABIOGEN PHARMA 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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Colecalciferol
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.3	Concentration number	1
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	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	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 Applicabile
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	ROACCUTAN 20*30CPS 20MG
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE 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	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oromucosal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Isotretinoin
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	40
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	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	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 Applicabile

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

MYELODISPLASTIC SYNDROME

SINDROMI MIELODISPLASTICHE

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10028533
E.1.2	Term	Myelodysplastic syndrome
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

To confront after 4 months of therapy the obtained eritroide RESPONSE with the conventional therapy with single rEPO to 40.000 U/week doses with that one obtained with the therapy of association between the same doses of rEPO and the therapy differentiating with acidio 13-cis-retinoico + DIIDROXILATE D3 vitamin.

Confrontare dopo 4 mesi di terapia la risposta eritroide ottenuta con la terapia convenzionale con sola rEPO a dosi di 40.000 unita'/settimana con quella ottenuta con la terapia di associazione tra le stesse dosi di rEPO e la terapia differenziante con acidio 13-cis-retinoico + vitamina D3 diidrossilata.

E.2.2

Secondary objectives of the trial

TO EVALUATED if, in the patients who have not obtained a eritroide RESPONSE to the 4ST month of therapy, the increase of dose of rEPO to 80.000 U/settimana allows to obtain an increment of RESPONSE estimated to the 8ST month. • TO EVALUATED THE difference of duration of the obtained eritroide RESPONSE with therapy rEPO ALONE regarding that one obtained with rEPO associated to therapy differentiating with 13-cis-retinoico acid + diidroXilatED D3 vitamin. • TO EVALUATED the existing relations between eritroide RESPONSE and clinician-biological parameters of debut which AMOUNT of the anemia, TYPE of MDS, SIERIC dosage of EPO etc • TO EVALUATED the induced improvement of the quality of life from the answer to the therapy. •TO EVALUATED the percentage of leucemica evolution.

• Valutare se,nei pazienti che non hanno ottenuto una risposta eritroide al termine del 4° mese di terapia,l'aumento di dose di rEPO a 80.000 U/settimana permette di ottenere un incremento di risposte valutate al termine dell'8° mese.• Valutare se esiste una differenza di durata della risposta eritroide ottenuta con terapia con sola rEPO rispetto a quella ottenuta con rEPO associata a terapia differenziante con acido 13-cis-retinoico + vitamina D3 diidrossilata.• Valutare le relazioni esistenti tra risposta eritroide e parametri clinico-biologici d'esordio quali entita' dell'anemia,sottoclasse di MDS,dosaggio serico dell'EPO ecc.• Valutare il miglioramento della quality of life indotto dalla risposta alla terapia.• Valutare la percentuale di evoluzione leucemica.

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

LIFE QUALITY:
Vers:
Date:
Title:
Objectives:

QUALITA DELLA VITA:
Vers:
Data:
Titolo:QOLQ-C30
Obiettivi:

E.3

Principal inclusion criteria

• OVER 18 years • Diagnosis confirmed from BONE MARROW biopsy AND ASPIRATE MEDULLARY • IPSS I OR II • INFERIOR value OF Hb to 11 g/dl. • Seric Value of rEPO < 500 mU/L • SIGNED informed Consent

• Eta' superiore a 18 anni • Diagnosi confermata da biopsia ossea e aspirato midollare di sindrome mielodisplastica senza eccesso di blasti: 'anemia refrattaria', 'anemia refrattaria con sideroblasti ad anello', 'citopenia refrattaria con displasia multilineare', 'citopenia refrattaria con displasia multilineare e sideroblasti ad anello' o 'sindrome del 5q-' senza eccesso di blasti, secondo la classificazione WHO (appendice ). • Score prognostico low o intermedio-1 secondo l'IPSS (appendice ) • Anemia con valore di Hb inferiore a 11 g/dl. • Valore di rEPO serica < 500 mU/L • Consenso informato alla partecipazione al protocollo.

E.4

Principal exclusion criteria

• Myelodisplastic Syndrome with excess of blasts (RAEB). • IPSS Intermediate-2 or high • Forecast of allogenic bone marrow transplant within 1 year from the diagnosis • Renal Insufficiency with advanced value of creatininemia to 3 times the normal limit. • Chronic Epatopatia with advanced value of bilirubinemia to 3 times the normal limit and/or advanced values of AST or STOP or ALP to 5 times the normal limit. • Other serious pathology or Presence neoplasia with life expectancy of inferior to 1 year . • Presence of neurological or psychiatric disorder • Allergy/intolerance to drugs employs. • Pregnant Women. • age < 18 years. • HIV+.

• Sindrome mielodisplastica con eccesso di blasti (RAEB). • Score IPSS intermedio-2 o alto (appendice ). • Previsione di trapianto di midollo allogenico entro 1 anno dalla diagnosi (pazienti di eta' inferiore a 60 anni, trasfusione - dipendenti o con grave leuco/piastrinopenia e con donatore famigliare HLA compatibile). L'indicazione a trapianto da donatore non-consanguineo, considerati i tempi comunemente necessari ad effettuare tale procedura, non costituisce controindicazione all'eventuale inserimento in questo protocollo di valutazione della risposta ad rEPO ; terapia differenziante. • Insufficienza renale con valore di creatininemia superiore a 3 volte il limite normale. • Epatopatia cronica con valore di bilirubinemia superiore a 3 volte il limite normale e/o valori di AST o ALT o ALP superiori a 5 volte il limite normale. • Presenza di seconda neoplasia o altra grave patologia con aspettativa di vita inferiore a 1 anno. • Presenza di patologie neurologiche o psichiatriche che rendano il paziente inaffidabile nell'assunzione dei farmaci. • Allergia / intolleranza nota ai farmaci impiegati. • Donne gravide. • Eta' < 18 anni. • Positivita' HIV.

E.5 End points

E.5.1

Primary end point(s)

ERYTROID RESPONSE

RISPOSTA ERITROIDE

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

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

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

E IN ASSOCIAZIONE CON ALTRI FARMACI - 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

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	No
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
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	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	136

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

2007-05-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-03-27

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

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