Clinical Trials Register

Summary
EudraCT Number:	2011-002732-70
Sponsor's Protocol Code Number:	YV25718
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:	2012-03-02
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

2011-002732-70

A.3

Full title of the trial

A phase IIIb parallel group, open label study of pegylated interferon alfa-2a monotherapy (PEG-IFN, Ro 25-8310) compared to untreated control in children with HBeAg positive chronic hepatitis B.

Studio di fase IIIb, a gruppi paralleli, in aperto, sulla monoterapia con interferone pegilato alfa-2a (PEG-IFN, Ro 25-8310) rispetto al controllo senza trattamento in bambini affetti da epatite B cronica HBeAg-positiva.

A.3.1

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

A Phase IIIb study to openly compare a group treated with only pegylated interferon alfa-2a (PEG-IFN) to an untreated group in children with chronic hepatitis B (CHB) who are HBeAg positive (a marker of their stage of CHB infection).

Uno studio di fase IIIb per confrontare in aperto un gruppo trattato con solo interferone pegilato alfa-2a (PEG-INF) con un gruppo non trattato in bambini con epatite cronica B con HBeAg positivo (un marcatore dello stadio dell'infezione dell'epatite B cronica).

A.3.2

Name or abbreviated title of the trial where available

PEARL

A.4.1

Sponsor's protocol code number

YV25718

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/169/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	F. HOFFMANN - LA ROCHE LTD.
B.1.3.4	Country	Switzerland
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	Hoffmann-La Roche
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Roche S.p.A.
B.5.2	Functional name of contact point	Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	Viale G.B. Stucchi 110
B.5.3.2	Town/ city	Monza
B.5.3.3	Post code	20900
B.5.3.4	Country	Italy
B.5.4	Telephone number	039 247 5070
B.5.5	Fax number	039 247 5084
B.5.6	E-mail	sergio.scaccabarozzi@roche.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	Pegasys
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	PEGINTERFERON ALFA-2A
D.3.9.1	CAS number	198153-51-4
D.3.9.2	Current sponsor code	RO 25-8310
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB16452MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	180
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	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

Treatment of HBeAg positive chronic hepatitis B (CHB) in children.

Trattamento dell'epatite B cronica HBeAg positiva in pazienti pediatrici.

E.1.1.1

Medical condition in easily understood language

HBeAg positive immunoactive Chronic(long-term)HepatitisB.Presence of HBeAg indicates early stage of disease.Immunoactive disease means the liver has started to become damaged by the virus.

Epatite B cronica immunoattiva HBeAg positiva. La presenza di HBeAg indica uno stadio iniziale di malattia. Immunoattiva significa che il fegato ha iniziato a essere danneggiato dal virus.

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

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	10008910
E.1.2	Term	Chronic hepatitis B
E.1.2	System Organ Class	10021881 - Infections and infestations

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 compare HBeAg seroconversion (loss of HBeAg and presence of anti-
HBe) between a group treated with PEG-IFN monotherapy and an
untreated control group.

Confrontare la sieroconversione dell'HBeAg (perdita dell'HBeAg e presenza di anti-HBe) tra un gruppo trattato con interferone pegilato alfa-2a (PEG-IFN) in monoterapia e un gruppo di controllo senza trattamento.

E.2.2

Secondary objectives of the trial

To examine the short and longer term effects on various efficacy and safety measures between a group treated with PEG-IFN monotherapy and an untreated control group, and to evaluate pharmacokinetics (PK) in PEG-IFN treated subjects.

Esaminare gli effetti a breve e lungo termine sulla base di vari parametri di efficacia e sicurezza tra un gruppo trattato con PEG-INF in monoterapia e un gruppo di controllo non trattato, e valutare la farmacocinetica nei pazienti trattati con PEG-INF.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male or female subjects aged 3 to <18 years old at baseline.
• Positive HBsAg for more than 6 months.
• Positive HBeAg and detectable HBV DNA at screening (subjects must have
>10,000 copies/mL [>2,000 IU/mL] as measured by PCR).
• Negative anti-HBs and anti-HBe at screening.
• A liver biopsy obtained within the past 2 years prior to baseline (and more than 6 months after the end of any previous therapy for Hepatitis B) to confirm the presence of advanced fibrosis or exclude cirrhosis
• Compensated liver disease (Child-Pugh Class A clinical classification)
• Elevated serum ALT >ULN but ≤ 10 × ULN as determined by two abnormal values taken ≥14 days apart during the six months before the first dose of study drug with at least one of the determinations obtained ≤35 days prior to the first dose. Reference range at local site should be used.
• Normal thyroid gland function at screening assessed by TSH, FT3, FT4, TPO antibodies and TBG determination.
• Signed informed consent from legal guardian and willingness of legal guardian to abide by the requirements of the study, and signed assent from child if appropriate.

• soggetti di sesso maschile o femminile di età pari o superiore a 3 anni e <18 anni al basale;
• HBsAg positivo per più di 6 mesi;
• HBeAg positivo e HBV DNA rilevabile allo screening (i soggetti devono avere >10.000 copie/ml [>2000 UI/ml] misurate tramite PCR);
• Anti-HBs e anti-HBe negativi allo screening;
• biopsia epatica eseguita nei 2 anni precedenti il basale (e più di 6 mesi dopo la conclusione di qualsiasi terapia precedente per l’epatite B) per confermare la presenza di fibrosi avanzata o per escludere la presenza di cirrosi;
• malattia epatica compensata (Classe A secondo la classificazione clinica Child-Pugh);
• innalzamento delle ALT sieriche a livelli >ULN ma ≤10 x ULN, determinato in base a due valori anormali rilevati a distanza di ≥14 giorni uno dall’altro nei sei mesi precedenti la prima dose di farmaco in studio, con almeno una delle misurazioni ottenute ≤35 giorni prima dell’inizio del trattamento in studio; deve essere utilizzato il range di riferimento adottato localmente dal centro;
• Funzionalità tiroidea nella norma allo screening, valutata mediante determinazione di TSH, FT3, FT4, anticorpi TPO e TBG;
• consenso informato firmato dal tutore legale e volontà del tutore legale di rispettare i requisiti dello studio e, se appropriato, assenso firmato dal bambino.

E.4

Principal exclusion criteria

•Subjects with cirrhosis
•Subjects who have received investigational drugs or licensed treatments with anti-HBV activity within 6 months prior to baseline (e.g. IFNs, systemic corticosteroids,
lamivudine, tenofovir, emtricitabine, adefovir, entecavir, telbivudine, systemic acyclovir, systemic famciclovir). (Exception: subjects who have had a limited (≤7 day) course of acyclovir for herpetic lesions more than 1 month before the study
baseline visit are not excluded.)
• Known hypersensitivity to PEG-IFN.
• Positive test results at screening for HAV IgM Ab, anti-HCV Ab, anti-HDV Ab or anti-HIV Ab.
• History or other evidence of a medical condition associated with chronic liver disease other than CHB.
• History or other evidence of bleeding from esophageal varices.
Decompensated liver disease (e.g. ascites, varices, Child-Pugh Class B or C clinical
classification).
• History or other evidence of metabolic liver disease.
• Suspicion of hepatocellular carcinoma on ultrasound or other liver imaging. (All subjects to have ultrasound during screening.)
• Screening Alfa-fetoprotein (AFP) ≥100 ng/mL.
• Screening neutrophil count <1.5 x 109 cells/L, platelet count <90 x 109 cells/L, or hemoglobin <11 g/dL for females and <12 g/dL for males.
• Screening serum creatinine concentration >1.5 x ULN for age or severe renal disease e.g. glomerulonephritis.
• Autoimmune hepatitis.
• History of immunologically mediated disease to include but not limited to:
inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus
erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, or clinical evidence of rheumatoid arthritis.
• Major depression or history of psychiatric disorder, such as major psychoses, suicidal ideation, and/or suicide attempt, where clinical trial participation would be
inappropriate.
• History or other evidence of chronic pulmonary or cardiac disease associated with clinically significant functional limitation.
• History of thyroid disease poorly controlled on prescribed medications.
• Poorly controlled diabetes.
• History of solid organ or bone marrow transplantation.
• Evidence of an active or suspected cancer or a history of malignancy in which the risk of recurrence was/is >20% within 2 years.
• History of having received any systemic anti-neoplastic (including radiation) or immunomodulatory treatment (including systemic corticosteroids) ≤6 months prior to
the study baseline visit or the expectation that such treatment will be needed at any time during the study. (Exception: Topical corticosteroids, corticosteroids
prescribed as physiological replacement therapies, or short courses [≤ 7 days] of
systemic corticosteroids.)
• Coagulopathy (international normalized ratio >1.5), hemoglobinopathy, hemophilia,
or history of severe illness or other blood disorders that would make subject
unsuitable for the study.
• History of seizure disorder requiring treatment with anticonvulsant medication
(excluding febrile seizures).
• History or other evidence of severe retinopathy.
• History or other evidence of severe illness or any other conditions which would make the subject, in the opinion of the investigator, unsuitable for the study.
• Active substance abuse within the last 6 months before the study.
• Sexually active females of childbearing potential and sexually active males who are not willing to utilize reliable contraception during the treatment/principal observation
period and during the initial 24 week follow-up period.
• Females of child bearing potential who have a positive urine or serum pregnancy test result within 24 hours of baseline, or who are breast-feeding.

• soggetti cirrotici;
• i pazienti che hanno ricevuto farmaci sperimentali o trattamenti autorizzati con attività anti-HBV nei 6 mesi precedenti la visita basale (es. interferoni, corticosteroidi sistemici, lamivudina, tenofovir, emtricitabina, adefovir, entecavir, telbivudina, aciclovir per via sistemica, famciclovir per via sistemica). (Eccezione: i soggetti che hanno ricevuto un ciclo limitato (≤7 giorni) di aciclovir per il trattamento di lesioni erpetiche più di 1 mese prima della visita basale non saranno esclusi);
• ipersensibilità nota a PEG-IFN;
• positività per HAV IgM Ab, anti-HCV Ab, anti-HDV Ab o anti-HIV Ab allo screening;
• storia o altra evidenza di una condizione medica associata a un’epatopatia cronica diversa da CHB;
• storia o altra evidenza di sanguinamento da varici esofagee;
• malattia epatica scompensata (es. asciti, varici, Classe B o C secondo la classificazione clinica Child-Pugh);
• storia o altra evidenza di malattia epatica metabolica;
• sospetto di carcinoma epatocellulare all’ecografia o a un altro esame di imaging del fegato (durante lo screening tutti i soggetti devono essere sottoposti a ecografia);
• alfa-fetoproteina (AFP) ≥100 ng/ml allo screening;
• conta dei neutrofili <1,5 x 109 cellule/l, conta piastrinica <90 x 109 cellule/l, oppure emoglobina <11 g/dl nelle femmine e <12 g/dl nei maschi allo screening;
• concentrazione di creatinina sierica allo screening >1,5 x ULN secondo l’età o grave malattia renale, es. glomerulonefrite;
• epatiti autoimmuni;
• storia di malattia immuno-mediata, incluse ma non solo: malattia infiammatoria intestinale, porpora trombocitopenica idiopatica, lupus eritematoso, anemia emolitica autoimmune, sclerodermia, psoriasi grave o evidenza clinica di artrite reumatoide;
• depressione maggiore o storia di disturbo psichiatrico come psicosi maggiori, ideazione suicidaria e/o tentato suicidio, che renderebbe inappropriata la partecipazione a uno studio clinico;
• storia o altra evidenza di malattia cronica polmonare o cardiaca associata a limitazione funzionale clinicamente significativa;
• storia di malattia tiroidea scarsamente controllata con la terapia farmacologica prescritta;
• diabete scarsamente controllato;
• storia di trapianto di organo solido o di midollo osseo;
• evidenza di un cancro attivo o sospetto o storia di una neoplasia maligna con rischio attuale/pregresso di recidiva >20% entro 2 anni;
• storia di trattamento con qualsiasi terapia sistemica antineoplastica (inclusa radioterapia) o immunomodulatoria (inclusi corticosteroidi sistemici) nel periodo ≤6 mesi precedente la visita basale dello studio o previsione della necessità di una terapia di questo tipo in qualsiasi momento dello studio. (Eccezione: corticosteroidi per via topica, corticosteroidi prescritti come terapia fisiologica sostitutiva, o brevi terapie [≤ 7 giorni] a base di corticosteroidi per via sistemica.);
• coagulopatia (rapporto internazionale normalizzato >1,5), emoglobinopatia, emofilia o storia di malattia grave o di altri disturbi ematologici che renderebbero il soggetto non idoneo per lo studio;
• storia di disturbo convulsivo richiedente il trattamento con farmaci anticonvulsivanti (escluse convulsioni febbrili);
• storia o altra evidenza di retinopatia grave;
• storia o altra evidenza di malattia grave o di qualsiasi altra condizione che, a giudizio dello sperimentatore, renderebbe il soggetto non idoneo per lo studio;
• abuso di qualsiasi sostanza attiva nei 6 mesi precedenti l’inizio dello studio;
• femmine sessualmente attive in età fertile e maschi sessualmente attivi che non acconsentono a utilizzare un metodo anticoncezionale affidabile durante il trattamento/il periodo principale di osservazione e nelle prime 24 settimane di F-U;
• femmine in età fertile positive al test di gravidanza (urine o siero) nelle 24 ore precedenti il basale.

E.5 End points

E.5.1

Primary end point(s)

HBeAg seroconversion (loss of HBeAg and presence of anti-HBe).

Sieroconversione HBeAg (perdita di HBeAg e comparsa di anti-HBe).

E.5.1.1

Timepoint(s) of evaluation of this end point

At the 24 week
post-treatment/principal observation period follow-up visit.

24 settimane dopo il trattamento/periodo principale di osservazione.

E.5.2

Secondary end point(s)

• Loss of HBeAg, HBsAg seroconversion (loss of HBsAg and presence of
anti-HBs), loss of HBsAg, quantitative serum ALT, proportion of normal
ALT, quantitative HBV DNA, suppression of HBV DNA <100,000 copies/mL (<20,000 IU/mL), <10,000 copies/mL (<2,000 IU/mL), undetectable and change from baseline, combined endpoint of HBeAg
seroconversion and HBV DNA <100,000 copies/mL (<20,000 IU/mL),
and combined endpoint of HBeAg seroconversion and HBV DNA <10,000
copies/mL (<2,000 IU/mL).
• Persistence HBeAg seroconversion (loss of HBeAg and presence of
anti-HBe).
• Descriptive change in liver elasticity (in liver elasticity sub-study subjects).
• Descriptive change in histological findings (in Group C advanced
fibrotic subjects only).

• Perdita di HBeAg, sieroconversione HBsAg (perdita di HBsAg e comparsa di anti-HBs), perdita di HBsAg, dosaggio quantitativo delle ALT sieriche, percentuale di ALT normali, determinazione quantitativa dell’HBV DNA, soppressione dell’HBV DNA a valori <100.000 copie/ml (<20.000 UI/ml), <10.000 copie/ml (<2000 UI/ml), a livelli non rilevabili e sua variazione rispetto al basale, endpoint combinato di sieroconversione HBeAg e HBV DNA <100.000 copie/ml (<20.000 UI/ml), ed endpoint combinato di sieroconversione HBeAg e HBV DNA <10.000 copie/ml (<2000 UI/ml)
• Persistenza della sieroconversione HBeAg (perdita di HBeAg e comparsa di anti-HBe).
• Variazione descrittiva dell’elasticità epatica (nei soggetti che partecipano al sottostudio di elasticità epatica centro-specifico).
• Variazione descrittiva dei referti istologici (solo nei soggetti del Gruppo C con fibrosi avanzata).

E.5.2.1

Timepoint(s) of evaluation of this end point

• At the end of treatment/principal observation period, at 24 weeks
after end of treatment/principal observation period, and at 1, 2, 3, 4 and 5 years after end of treatment/principal observation period.
• At the end of treatment/principal observation period, and at 1, 2, 3, 4
and 5 years after end of treatment/principal observation period.
• At 24 weeks and 2 years after end of treatment/principal observation period.
• At 24 weeks after end of treatment.

- Alla fine del trattamento/periodo principale di osservazione, a 24 settimane dopo la fine del trattamento/periodo principale di osservazione e a 1, 2, 3, 4 e 5 anni dopo la fine del trattamento/periodo principale di osservazione.
- alla fine del trattamento/periodo principale di osservazione e a 1, 2, 3, 4 e 5 anni dopo la fine del trattamento/periodo principale di osservazione.
- a 24 settimane e a 2 anni dopo la fine del trattamento/periodo principale di osservazione.
- a 24 settimane dopo la fine del trattamento.

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

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)

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

braccio osservazionale

observational arm

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

Australia

Brazil

China

Israel

Malaysia

Russian Federation

Ukraine

United States

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

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

114

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

Number of subjects for this age range:

160

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)

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 aged 3 to <18 years of age. Signed informed consent from
legal guardian and willingness of legal guardian to abide by the
requirements of the study, and signed assent from child if appropriate.

Bambini di età compresa tra i 3 ai 17 anni. Consenso Informato scritto da parte del legale rappresentante e volantà del legale rappresentante di aderire ai requisiti dello studio, assenso scritto del bambino, se appropriato.

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

160

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)

4,5 years of follow-up.

4,5 anni di follow-up.

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

2012-01-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-10-18

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