Clinical Trials Register

Summary
EudraCT Number:	2011-006058-94
Sponsor's Protocol Code Number:	CAIN457F2311
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:	2012-09-13
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

2011-006058-94

A.3

Full title of the trial

A Phase III randomized, double-blind, placebo-controlled multicenter study of subcutaneous secukinumab in prefilled syringes to demonstrate the efficacy at 24 weeks and to assess the long term efficacy, safety, tolerability and usability up to 5 years in patients with active rheumatoid arthritis who have an inadequate response to anti-TNFα agents

Studio multicentrico di fase III, randomizzato, in doppio cieco, controllato verso placebo per dimostrare l efficacia a 24 settimane di secukinumab, somministrato sottocute mediante siringhe pre-riempite, e per valutare l efficacia, la sicurezza, la tollerabilita e l usabilita a lungo termine fino a 5 anni in pazienti con artrite reumatoide attiva che presentano una risposta inadeguata ai farmaci anti-TNF± Tipo di

A.3.1

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

Secukinumab efficacy and safety study in patients with active Rheumatoid Arthritis (RA) and an Inadequate response to anti-TNFα agents

Secukinumab,studio di efficacia e sicurezza in pazienti con artrite reumatoide attiva che presentano una risposta inadeguata ai farmaci anti-TNFα

A.4.1

Sponsor's protocol code number

CAIN457F2311

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
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
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.studiclinici@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	AIN457F
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	SECUKINUMAB
D.3.9.1	CAS number	1229022-83-6
D.3.9.2	Current sponsor code	AIN457
D.3.9.4	EV Substance Code	SUB33242
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	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.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	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	AIN457F
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	SECUKINUMAB
D.3.9.1	CAS number	1229022-83-6
D.3.9.2	Current sponsor code	AIN457
D.3.9.4	EV Substance Code	SUB33242
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	75
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
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

Rheumatoid arthritis

Artrite Reumatoide

E.1.1.1

Medical condition in easily understood language

Rheumatoid arthritis

Artrite Reumatoide

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	PT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective 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

Measure the proportion of subjects achieving an ACR20 response compared to placebo at week 24.

Dimostrare che l’efficacia di secukinumab 75 mg o 150 mg somministrato alla settimana 24 è superiore a placebo nei pazienti con AR attiva, basata sulla proporzione di pazienti che raggiungono la risposta ACR 20

E.2.2

Secondary objectives of the trial

1) Measure the proportion of subjects achieving an ACR50 response compared to placebo at week 24 2) Measure the disability assessment component of the HAQ (Health Assessment Questionnaire – Disability Index) at week 24 compared to baseline.

1) Dimostrare che l’efficacia di secukinumab 75 mg o 150 mg alla settimana 24 è superiore al placebo in pazienti con AR attiva basata sulla proporzione di soggetti che raggiungono la risposta ACR50; 2) Dimostrare che l’efficacia di secukinumab 75 mg o 150 mg alla settimana 24 è superiore al placebo nel miglioramento (variazione) rispetto al basale del questionario HAQ-DI .

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

PHARMACOGENETIC:
Vers:v00
Date:2012/06/07
Title:Pharmacogenetics/Biomarkers study in the protocol : A Phase III randomized, double-blind, placebo-controlled multicenter study of subcutaneous secukinumab in prefilled syringes to demonstrate the efficacy at 24 weeks and to assess the long term efficacy, safety, tolerability and usability up to 5 years in patients with active rheumatoid arthritis who have an inadequate response to anti-TNFα agents
Objectives:Complementary study of pharmacogenetics The objectives of this exploratory study are 1) to find genetic markers that will identify subjects with rheumatoid arthritis that they will have the best possible answer to secukinumab (AIN457) and 2) to identify the subjects that will have the smaller drawbacks so they give to be able to supply they the maximum the benefit from the administration of secukinumab (AIN457

FARMACOGENETICA:
Vers:v00
Data:2012/06/07
Titolo:Studio complementare di farmacogenetica e biomarcatori inserito nel protocollo: Studio multicentrico di fase III, randomizzato, in doppio cieco, controllato verso placebo per dimostrare l’efficacia a 24 settimane di secukinumab, somministrato sottocute mediante siringhe pre-riempite, e per valutare l’efficacia, la sicurezza, la tollerabilità e l’usabilità a lungo termine fino a 5 anni in pazienti con artrite reumatoide attiva che presentano una risposta inadeguata ai farmaci anti-TNFα
Obiettivi:Studio complementare di farmacogenetica Gli obiettivi di questo studio esploratorio sono 1) trovare marcatori genetici che identificheranno soggetti con artrite reumatoide che avranno la miglior risposta possibile a secukinumab (AIN457) e 2) identificare i soggetti che avranno i minori effetti collaterali così da poter fornire loro il massimo il beneficio dalla somministrazione di secukinumab (AIN457).

E.3

Principal inclusion criteria

1) Presence of Rheumatoid Arthritis classified by ACR 2010 revised criteria for at least 3 months 2) Disease activity defined by ≥6 tender joints out of 68 and ≥ 6 swollen joints out of 66 at baseline and with: either Anti-CCP antibodies positive OR Rheumatoid Factor positive and with either hsCRP ≥ 10 mg/L OR ESR ≥28 mm/1st hr 3) Intake of at least one anti-TNF-α agent such as etanercept, adalimumab, infliximab, certolizumab or golimumab for at least 3 months before entering the study and to have experienced an inadequate response to treatment or to have been intolerant to at least one administration Other protocol-defined inclusion criteria may apply

• Pazienti in grado di comprendere e comunicare con il medico sperimentatore, di ottemperare ai requisiti dello studio e di fornire il proprio consenso informato scritto prima dell’effettuazione di qualsiasi procedura di studio • Maschi, o femmine non gravide nè in allattamento, di almeno 18 anni di età • Diagnosi di artrite reumatoide da almeno 3 mesi prima della visita di screening, classificata in accordo con i criteri revisionati ACR 2010 • Al basale: attività di malattia definita da ≥ 6 articolazioni doloranti (su 68) e ≥ 6 articolazioni gonfie (su 66) con almeno uno dei seguenti parametri allo screening o Anticorpi anti-CCP positivi oppure o Fattore reumatoide positivo e con almeno uno dei seguenti parametri allo screening o hsPCR ≥ 10 mg/L oppure o VES ≥ 28 mm/1° ora • Trattamento con almeno un agente anti-TNFα (quale etanercept, adalimumab, infliximab, certolizumab o golimumab) ad una dose appropriata per almeno 3 mesi prima della randomizzazione, con una risposta terapeutica inadeguata o un’intolleranza ad almeno una somministrazione

E.4

Principal exclusion criteria

1) Current RA functional status class IV according to the ACR 1991 revised criteria 2) Previous use of secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor and/or any history of hypersensitivity to secukinumab or its excipient or to drugs of similar chemical classes 3) Subjects who have ever received biologic immunomodulating agents except for those targeting TNFα Other protocol-defined exclusion criteria may apply

I pazienti che presentano uno qualsiasi dei seguenti criteri non sono eleggibili all’inclusione in questo studio: • Radiografia del torace o risonanza magnetica, eseguite nei 3 mesi precedenti lo screening e valutate da un medico qualificato, con evidenza di processi infettivi o neoplasie in atto • Diagnosi di AR con status funzionale di classe IV in accordo con i criteri ACR 1991 revisionati • assunzione di analgesici oppioidi ad elevata potenza, ad esempio metadone, idromorfone, morfina. • Precedente esposizione a secukinumab o ad altri farmaci diretti contro la interleuchina 17 o il suo recettore • Uso di qualsiasi farmaco sperimentale e/o dispositivi nelle 4 settimane precedenti la randomizzazione o in un periodo pari a 5 emivite del farmaco sperimentale, considerando il periodo più lungo

E.5 End points

E.5.1

Primary end point(s)

ACR20

E.5.1.1

Timepoint(s) of evaluation of this end point

week 24

settimana 24

E.5.2

Secondary end point(s)

1) ACR50 2) Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)

E.5.2.1

Timepoint(s) of evaluation of this end point

1) week 24 2) Week 0 (BSL) and week 24

1) settimana 24 2) settimana 0 (BSL) e settimana 24

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

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

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)

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

Brazil

Colombia

Dominican Republic

Ecuador

Guatemala

India

Korea, Republic of

Panama

South Africa

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 : 31/AUG/2018

LVLS : 31/AGO/2018

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:

187

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

F.4.2.2

In the whole clinical trial

234

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)

The investigator must provide follow-up medical care for all subjects who leave the study, or must refer them for appropriate ongoing care. This care may include initiating another treatment outside of the study as deemed appropriate by the investigator. This treatment may be any non-biologic DMARD. In case of a biologic treatment, a waiting period of 3 months before initiating the treatment is recommended.

Il ricercatore deve fornire l'assistenza medica necessaria a tutti i soggetti che lasciano lo studio, o devono farli riferimento per la cura più appropriata. Questa cura può comprendere l'inizio di un altro trattamento fuori dello studio come meglio ritenuto appropriato dal ricercatore. Questo trattamento può essere DMARD non biologico. Nel caso di un trattamento biologico, un periodo di attesa di 3 mesi prima dell'inizio del nuovo trattamento biologico è fortemente raccomandato.

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

2012-09-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-09-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-05-11

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