Clinical Trials Register

Summary
EudraCT Number:	2010-022884-36
Sponsor's Protocol Code Number:	EPOANE3021
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:	2012-01-23
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2010-022884-36

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating Epoetin Alfa Versus Placebo in Anemic Patients With IPSS Low- or Intermediate 1 Risk Myelodysplastic Syndromes

Uno studio randomizzato, in doppio cieco, multicentrico, controllato da placebo, per valutare l'effetto di epoetina alfa rispetto al placebo in pazienti anemici con sindromi mielodisplastiche con rischio IPSS basso o intermedio-1

A.3.1

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

A clinical study comparing Epoetin Alfa with Placebo in Anaemic patients with MDS

Studio clinico per confrontare l'effetto di Epoetina Alfa verso l'effetto del placebo in pazienti anemici con sindromi mielodisplastiche

A.4.1

Sponsor's protocol code number

EPOANE3021

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	JANSSEN-CILAG INTERNATIONAL N.V.
B.1.3.4	Country	Belgium
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	JANSSEN CILAG SPA
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	JANSSEN CILAG SPA
B.5.2	Functional name of contact point	CGO
B.5.3	Address:
B.5.3.1	Street Address	VIA M. BUONARROTI 23
B.5.3.2	Town/ city	COLOGNO MONZESE
B.5.3.3	Post code	20093
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39 022510 569
B.5.5	Fax number	+39 02 2510 537
B.5.6	E-mail	scazzani@its.jnj.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	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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.9.1	CAS number	113427-24-0
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international 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
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

Anemia due to IPSS Low- or Intermediate-1-Risk Myelodysplastic Syndromes

Anemia causata da sindromi mielodisplastiche con rischio IPSS basso o intermedio-1

E.1.1.1

Medical condition in easily understood language

Anemia due to Myelodysplastic Syndromes

Anemia dovuta a malattie 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	LLT
E.1.2	Classification code	10002272
E.1.2	Term	Anemia
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is:  To demonstrate that epoetin alfa treatment is better at improving anemia outcome (as evaluated by Erythroid response – International Working Group [IWG] 2006) in subjects with International Prognostic Scoring Systems (IPSS) Low- or Intermediate-1-risk myelodysplastic syndromes (MDS), compared with placebo, through Week 24.

L'obiettivo principale è il seguente: • Dimostrare che, nell’arco di 24 settimane, il trattamento con epoetina alfa, rispetto al placebo, è migliore nel correggere l'anemia (valutazione che verrà effettuata in base alla risposta eritroide - International Working Group [IWG] 2006) in soggetti con sindromi mielodisplastiche (SMD) con rischio IPSS (International Prognostic Scoring Systems, sistema internazionale di punteggio prognostico) Basso o Intermedio-1.

E.2.2

Secondary objectives of the trial

The secondary objectives include: • For responders at Week 24, observe the duration of the response through Week 48. • To assess the proportion of responders at Week 24 maintaining response through Week 48 (as measured by Erythroid response – IWG 2006). • To compare time to first RBC transfusion, transfusion-free intervals, and number of RBC units transfused. • To measure and compare changes in patient-reported outcome (PRO)/quality of life from baseline via the Functional Assessment of Cancer Therapy  Anemia/Fatigue (FACT-An) and EuroQol 5 dimension (EQ-5D) questionnaires. • To collect medical resource utilization data that may be used in future economic modeling (the construction and reporting of the economic model will be conducted separately from this study). Overall safety will also be assessed.

• Per i responder alla settimana 24, osservazione della durata della risposta fino alla settimana 48. • Valutazione della proporzione di responder alla settimana 24 che mantengono la risposta fino alla settimana 48 (la valutazione verrà effettuata in base alla risposta eritroide - IWG 2006). • Confronto dei tempi alla prima trasfusione di globuli rossi (RBC), intervallo libero da trasfusioni, e numero di unità di RBC trasfuse. • Misura e confronto delle variazioni, dalla visita basale, dei risultati riportati dal paziente (PRO, patient-reported outcome) e della qualità della vita mediante i questionari Functional Assessment of Cancer Therapy  Anemia/Fatigue (FACT-An) e EuroQol 5 dimension (EQ-5D). • Raccolta di dati sull'utilizzo delle risorse mediche, da impiegare per la creazione di futuri modelli economici. Verrà valutata anche la sicurezza generale.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male or female subjects at least18 years of age; • diagnosis of MDS at screening, according to World Health Organization (WHO) or French-American-British (FAB) Cooperative Group pathologic classification and confirmed via bone marrow aspirate; • documentation of an IPSS score indicating Low- or Intermediate 1 risk disease; • hemoglobin concentration at screening and baseline (before the first dose of study drug) of 10.0 g/dL or less, based on untransfused hemoglobin (ie, the subject did not receive an RBC transfusion within the previous week); • screening serum erythropoietin concentration of less than 500 mU/mL; • RBC transfusion requirement of less than 4 RBC units over the last 8 weeks before randomization; • screening Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2; • adequate iron stores, defined as serum ferritin greater than 100 ng/mL, transferrin saturation greater than 20%, or both, measured within the 2-week screening period, or adequate iron stores as demonstrated by recent (within 12 weeks) bone marrow examination with iron stain; • documentation of adequate vitamin B12 and folate levels (above the lower limit of the reference range for the laboratory performing the assay), measured at screening and baseline.

• soggetti maschi o femmine di almeno 18 anni d'età; • diagnosi di SMD allo screening, secondo la classificazione patologica dell'Organizzazione Mondiale della Sanità (WHO) o del gruppo cooperativo Franco-Americano-Britannico (FAB) e confermato tramite agoaspirato del midollo osseo; • documentazione di un punteggio IPSS che indica una malattia a rischio basso o intermedio-1; • concentrazione di emoglobina alla visita di screening e basale (precedentemente alla prima dose del farmaco dello studio) di 10,0 g/dL o inferiore, sulla base dell'emoglobina non trasfusa (ovvero il soggetto non ha ricevuto una trasfusione di RBC nella precedente settimana); • concentrazione di eritropoietina nel siero alla visita di screening inferiore a 500 mU/mL; • necessità trasfusionale di RBC inferiore a 4 unità di RBC nelle 8 settimane precedenti la randomizzazione; • performance status ECOG (Eastern Cooperative Oncology Group) allo screening pari a 0, 1 o 2; • riserve di ferro adeguate, definite come ferritina nel siero superiore a 100 mg/mL o saturazione della transferrina superiore al 20% o entrambe, con valutazione effettuata nel periodo di 2 settimane dello screening oppure riserve di ferro adeguate come dimostrato da un recente esame del midollo osseo (entro 12 settimane) con colorazione per il ferro; • documentazione di livelli adeguati di vitamina B12 e folato (al di sopra del limite inferiore del range di riferimento per il laboratorio, che esegue la valutazione), in base alla valutazione effettuata allo screening e alla visita basale.

E.4

Principal exclusion criteria

• Anemia attributed to factors other than MDS; • secondary MDS (ie, MDS arising after chemotherapy, immunotherapy, or radiation therapy/exposure; • active malignancy within the past year, except basal cell or carcinoma in situ of the cervix or breast; • prior therapy with epoetin alfa or any other approved or experimental ESA for more than 8 weeks before randomization; • prior use of approved or experimental agents for the treatment of MDS; • history (within 6 months) of deep vein thrombosis (including proximal and distal), pulmonary embolism, or other venous thrombosis.

• anemia attribuita a fattori diversi da SMD; • SMD secondaria (ovvero SMD che si manifesta in seguito a chemioterapia, immunoterapia o radioterapia/esposizione a radiazioni); • patologia maligna attiva nell’anno precedente, esclusi il carcinoma basocellulare o il carcinoma in situ della cervice o del seno; • precedente terapia con epoetina alfa o qualsiasi altro ESA, approvato o sperimentale, per più di 8 settimane prima della randomizzazione; • precedente utilizzo di agenti approvati o sperimentali per il trattamento della SMD; • storia (nei 6 mesi precedenti) di trombosi venosa profonda (sia prossimale che distale), embolia polmonare o altra trombosi venosa.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the proportion of subjects at Week 24 with improved anemia outcome, defined as Erythroid response according to the IWG 2006 criteria.

L'endpoint primario di efficacia è la proporzione di soggetti che alla settimana 24 registrano un miglioramento dell'anemia, definito come risposta eritroide secondo i criteri IWG 2006.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks

24 settimane

E.5.2

Secondary end point(s)

• For responders at Week 24, the duration of the response through Week 48 • The proportion of responders at Week 24 maintaining response through Week 48 (as measured by Erythroid response – IWG 2006). • Time to first RBC transfusion, transfusion-free intervals, and number of RBC units transfused. • Change from baseline in PRO/quality of life (as assessed with the FACT-An and EQ-5D).

• Per i responder alla settimana 24, la durata della risposta fino alla settimana 48. • La proporzione di responder alla settimana 24 che mantengono la risposta fino alla settimana 48 (valutato in base alla risposta eritroide - IWG 2006). • Il tempo alla prima trasfusione di globuli rossi (RBC), gli intervalli liberi da trasfusioni ed il numero di unità di RBC trasfuse. • La variazione dalla visita basale nei questionari PRO/qualità della vita (valutata con i questionari FACT-An e EQ-5D).

E.5.2.1

Timepoint(s) of evaluation of this end point

48 weeks

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

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

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

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

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

Russian Federation

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

last visit of last subject

ultima visita dell'ultimo paziente arruolato

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:

111

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.4.2

For a multinational trial

F.4.2.1

In the EEA

147

F.4.2.2

In the whole clinical trial

159

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)

standard care

pratica clinica standard

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

2011-06-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-01-06

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials