Clinical Trials Register

Summary
EudraCT Number:	2010-022228-66
Sponsor's Protocol Code Number:	CAIN457A2303
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:	2011-12-28
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

2010-022228-66

A.3

Full title of the trial

A randomized, double-blind, double-dummy, placebo controlled, multicenter study of subcutaneous secukinumab to demonstrate efficacy after twelve weeks of treatment, compared to placebo and etanercept, and to assess the safety, tolerability and long-term efficacy up to one year in subjects with moderate to severe chronic plaque-type psoriasis. FIXTURE (Full year Investigative eXamination of secukinumab vs eTanercept Using 2 dosing Regimens to determine Efficacy in psoriasis)

Studio multicentrico, randomizzato, in doppio cieco, double dummy, controllato verso placebo, per dimostrare la efficacia dopo dodici settimane di trattamento con secukinumab sottocute, rispetto a placebo ed etanercept, e per valutare la sicurezza, la tollerabilita' e la efficacia a lungo termine fino ad un anno in soggetti con psoriasi cronica a placche da moderata a severa. Studio FIXTURE

A.3.1

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

Safety and Efficacy of Secukinumab Compared to Etanercept in Subjects with Moderate to Severe, Chronic Plaque-Type Psoriasis

Sicurezza ed efficacia di Secukinumab in confronto a Etarnecerpt in soggetti con psoriasi cronica a placche da moderata a severa.

A.4.1

Sponsor's protocol code number

CAIN457A2303

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	NOVARTIS FARMA
B.1.3.4	Country	Italy
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	Novartis Pharma
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	Novartis Farma
B.5.2	Functional name of contact point	Drug Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Largo Umberto Boccioni, 1
B.5.3.2	Town/ city	Origgio (VA)
B.5.3.3	Post code	21040
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39 02 96541
B.5.5	Fax number	+39 02 9659066
B.5.6	E-mail	info.italia@novartis.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	No
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.3.1	Product name	Secukinumab
D.3.2	Product code	AIN457
D.3.4	Pharmaceutical form	Powder for 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.3.9.2	Current sponsor code	AIN457
D.3.9.3	Other descriptive name	Secukinumab
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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.IMP: 2
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	ENBREL*SC 4SIR 50MG 1ML+8TAMP
D.2.1.1.2	Name of the Marketing Authorisation holder	WYETH LEDERLE 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	ETANERCEPT
D.3.9.1	CAS number	185243690
D.3.9.4	EV Substance Code	SUB01984MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	Powder for solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
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

Moderate to severe chronic plaque-type psoriasis

Psoriasi cronica a placche da moderata a severa

E.1.1.1

Medical condition in easily understood language

Psoriasis looks like red, raised scaly areas of the skin

La psoriasi si presenta con zone arrossate, sollevate, squamose della pelle

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

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	10037153
E.1.2	Term	Psoriasis
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

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	10050577
E.1.2	Term	Psoriatic plaque
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue 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

Efficacy of secukinumab compared to placebo in subjects with moderate to severe chronic plaque-type psoriasis over 12 weeks based on PASI and IGA

Dimostrare la superiorità di secukinumab rispetto al placebo alla Settimana 12, in soggetti con psoriasi cronica a placche da moderata a severa secondo la risposta PASI 75 e la valutazione IGA 0 o 1 (endpoint co-primari) .

E.2.2

Secondary objectives of the trial

- Efficacy of secukinumab compared to etanercept in subjects with moderate to severe chronic plaque-type psoriasis over 12 weeks based on PASI and IGA - Clinical safety and tolerability of secukinumab compared to etanercept and placebo over 12 weeks - Quality of life changes based on patient reported outcomes over 12 and 52 weeks

• Dimostrare la non inferiorità di secukinumab rispetto ad etanercept alla Settimana 12 in soggetti con psoriasi cronica a placche da moderata a severa secondo la risposta PASI 75 • Dimostrare la superiorità di secukinumab rispetto al placebo alla settimana 12 in soggetti con psoriasi cronica a placche da moderata a severa secondo la risposta PASI 90 Dimostrare la superiorità di di secukinumab rispetto ad etanercept alla Settimana 12, in soggetti con psoriasi cronica a placche da moderata a severa secondo la risposta PASI 75 e la valutazione IGA 0 o 1 Dimostrare la superiorità di secukinumab rispetto ad etanercept nel mantenere la risposta PASI 75 alla Settimana 52 per i soggetti che raggiungono il PASI 75 alla Settimana 12 • PER FAVORE VEDERE SINOSSI

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Subjects with chronic, plaque-type psoriasis for at least 6 months • Must have moderate to severe psoriasis based on PASI greater than 12, IGA greater than 3, and greater than 10% body surface area • Must be inadequately controlled by prior treatments (topicals, phototherapy, and/or systemic therapies) Other protocol-defined inclusion criteria may apply.

1. Soggetti in grado di comprendere e di comunicare con lo sperimentatore e in grado di aderire ai requisiti dello studio (compresa la somministrazione di iniezioni s.c. a domicilio) e che hanno dato il proprio consenso informato scritto, firmato e datato prima dell’effettuazione di qualsiasi attività correlata allo studio. 2. Uomini o donne di almeno 18 anni di età al momento dello screening 3. Psoriasi cronica a placche diagnosticata almeno 6 mesi prima della randomizzazione 4. Psoriasi da moderata a severa come definita alla randomizzazione da: • Punteggio PASI di 12 o maggiore e, • Punteggio IGA mod 2011 di 3 o maggiore (sulla base di una scala 0-4) e, • BSA interessata dalla psoriasi a placche del 10% o maggiore 5. Soggetti candidati per la terapia sistemica, definiti come soggetti con psoriasi cronica a placche considerata non adeguatamente controllata tramite: • Trattamento topico e/o • Fototerapia e/o • Precedente terapia sistemica

E.4

Principal exclusion criteria

• Forms of psoriasis other than chronic, plaque-type (such as pustular, erythrodermic and guttate psoriasis) • Drug induced psoriasis • Use of other psoriasis treatments during the study • Prior use of etanercept • Prior use of secukinumab or any other drug that target IL-17 or the IL- 17 receptor • Pregnant or lactating women; women who do not agree to use contraception during the study and for 16 weeks after stopping treatment • Significant medical problems such as uncontrolled high blood pressure, congestive heart failure, etc. • History of an ongoing, chronic or recurrent infection or evidence of tuberculosis • Allergy to rubber or latex Other protocol-defined exclusion criteria may apply.

1. Forme di psoriasi diverse dalla psoriasi cronica a placche (ad esempio psoriasi pustolosa, eritrodermica e guttata) 2. Psoriasi indotta da farmaci (cioè di nuova insorgenza o esacerbazione in atto causata da betabloccanti, inibitori del canale del calcio o litio) 3. Uso corrente di trattamenti proibiti per la psoriasi (ad esempio corticosteroidi per uso topico o sistemico, terapia UV). Devono essere rispettati i periodi di wash-out dettagliati nel protocollo (Tabella 5-1) 4. Uso corrente di altri trattamenti proibiti non per la psoriasi. Devono essere rispettati i periodi di wash-out dettagliati nel protocollo (Tabella 5-1). Tutti gli altri trattamenti precedenti concomitanti non per la psoriasi devono essere a dose stabile da almeno quattro settimane prima della randomizzazione 5. Precedente esposizione a secukinumab o qualsiasi altro farmaco biologico avente come target diretto IL-17 o il recettore di IL-17 6. Precedente esposizione a etanercept 7. Donne in gravidanza o allattamento, dove la gravidanza è definita come lo stato di una donna dopo il concepimento e fino al termine della gestazione, confermato da un test di laboratorio positivo per hCG (> 5 mlU/mL) 8. Donne potenzialmente fertili, definite come tutte le donne fisiologicamente in grado di iniziare una gravidanza a meno che non utilizzino metodi contraccettivi efficaci durante lo studio e per 16 settimane dopo l’interruzione del trattamento. La contraccezione efficace è definita come: • Metodo di barriera: preservativo o cappuccio occlusivo (diaframma o cappuccio cervicale) con spermicida (laddove disponibile). Nota: gli spermicidi da soli non costituiscono un metodo contraccettivo di barriera e non devono essere utilizzati come unico metodo. I seguenti metodi sono considerati più efficaci del metodo di barriera e sono anch’essi accettabili: • Astinenza totale: quando ciò è in linea con lo stile di vita preferito e abituale del soggetto [l’astinenza periodica (ad esempio metodi basati sul calendario, sull’ovulazione, metodi sintotermici e post-ovulazione) e il coito interrotto non sono considerati metodi contraccettivi accettabili] • Sterilizzazione femminile: soggetti che sono stati sottoposti a ooforectomia bilaterale chirurgica (con o senza isterectomia) o legatura delle tube almeno sei settimane prima dell’assunzione del trattamento in studio. In caso di sola ooforectomia, solo quando lo stato riproduttivo della donna è stato confermato da una valutazione del livello ormonale • Sterilizzazione del partner maschile (con appropriata documentazione post-vasectomia di assenza di sperma nell’eiaculato). [Per i soggetti femminili in studio, il partner sottoposto a vasectomia deve essere l’unico partner] • Uso di metodi contraccettivi ormonali orali, iniettabili o impiantabili consolidati, dispositivo intrauterino (IUD) o sistema intrauterino (IUS) Nota: Le donne sono considerate in fase post-menopausa e non potenzialmente fertili se hanno avuto 12 mesi di amenorrea naturale (spontanea) con appropriato profilo clinico (ad esempio età adeguata, storia di sintomi vasomotori) o sei mesi di amenorrea spontanea con livelli sierici FSH > 40 mlU/mL 9. Patologie infiammatorie attive in corso diverse dalla psoriasi che potrebbero mascherare la il beneficio della terapia con secukinumab 10. Condizioni di fondo del paziente (incluso ad esempio condizioni metaboliche, ematologiche, renali, epatiche, polmonari, neurologiche, endocrine, cardiache, infettive o gastrointestinali) che, secondo il parere dello sperimentatore, possono immunocompromettere il soggetto in modo significativo e/o esporlo ad un rischio inaccettabile di ricevere una terapia immunomodulatoria 11. I soggetti con pregressa o recente insorgenza di disordini demielinizzanti del sistema nervoso centrale o periferico saranno valutati a discrezione dello sperimentatore 12. Per favore vedere sinossi

E.5 End points

E.5.1

Primary end point(s)

PASI and IGA

PASI e IGA

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks

12 settimane

E.5.2

Secondary end point(s)

- PASI and IGA - Clinical safety and tolerability of secukinumab - Quality of life changes

- PASI e IGA - Sicurezza e tollerabilità clinica di secukinumab - Qualità della vita

E.5.2.1

Timepoint(s) of evaluation of this end point

Respectively : - 12 weeks - 12 weeks - 12 and 52 weeks

rispettivamente : - 12 settimane - 12 settimane - 12 e 52 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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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

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)

Yes

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

Argentina

Australia

Brazil

Canada

Colombia

Guatemala

India

Korea, Republic of

Peru

Russian Federation

Singapore

Turkey

United States

Venezuela, Bolivarian Republic of

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 : 06/MAY/2013

LVLS : 06/05/2013

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:

1201

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

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

486

F.4.2.2

In the whole clinical trial

1264

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)

When the subject leaves the study, the investigator will discuss the different medications or possible alternatives that are available to treat the subject's psoriasis.

Quando il soggetto lascierÃ lo studio, le verrano proposte dal ricercatore farmaci differenti o alternative possibili che sono disponibili per il trattamento della psoriasi del soggetto.

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

2011-06-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-04-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-07-07

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