Clinical Trials Register

Summary
EudraCT Number:	2011-000102-21
Sponsor's Protocol Code Number:	CAIN457F2309
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:	2012-01-09
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

2011-000102-21

A.3

Full title of the trial

A randomized, double-blind, placebo- and active-controlled study of secukinumab to demonstrate the efficacy at 24 weeks and to assess the safety, tolerability and long term efficacy up to 1 year in patients with active rheumatoid arthritis who have an inadequate response to anti-TNFα agents

[Studio randomizzato, in doppio cieco, controllato verso placebo e farmaco attivo per dimostrare l'efficacia di secukinumab a 24 settimane e valutarne la sicurezza, la tollerabilita' e l'efficacia prolungata ad un anno in pazienti con artrite reumatoide attiva con risposta inadeguata ad agenti anti-TNF]

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 placebo and abatacept in patients with active rheumatoid arthritis who did not respond to anti- TNFα agents

La sicurezza e l'efficacia di secukinumab in confronto a placebo e a abatacept in pazienti con l'artrite reumatoide attiva che non ha risposto ad anti- Agenti di TNFα

A.4.1

Sponsor's protocol code number

CAIN457F2309

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.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	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Secukinumab
D.3.9.2	Current sponsor code	AIN457
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	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	ORENCIA*IV 2FL 250MG+2SIR
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL-MYERS SQUIBB Srl
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	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ABATACEPT
D.3.9.1	CAS number	332348-12-6
D.3.9.4	EV Substance Code	SUB20635
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	250
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	Intravenous 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	14.1
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

Demonstrate the efficacy of secukinumab (75 or 150 mg) versus placebo (measured with ACR 20) after 24 weeks of treatment

Dimostrare, sulla base della proporzione di pazienti che raggiunge una risposta ACR20 alla settimana 24, che l’efficacia di secukinumab 75 mg o 150 mg è superiore a placebo in pazienti con AR attiva

E.2.2

Secondary objectives of the trial

- Change of the HAQ-DI from baseline on secukinumab 75 mg or 150 mg compared to placebo after 24 weeks of treatment - Proportion of patients achieving major clinical response on secukinumab 75 mg or 150 mg compared to placebo after 1 year of treatment - Proportion of patients achieving an ACR 20 response on secukinumab 75 mg or 150 mg compared to abatacept after 24 weeks of treatment - Change of the HAQ-DI from baseline on secukinumab 75 mg or 150 mg compared to abatacept after 24 weeks of treatment - Proportion of patients achieving major clinical response on secukinumab 75 mg or 150 mg compared to abatacept after 1 year of treatment

• dimostrare che a 24 settimane di trattamento, secukinumab 75 o 150 mg è in grado di apportare un miglioramento superiore a placebo rispetto al basale sulla base del questionario di valutazione della malattia (HAQ-DI) • dimostrare che secukinumab 75 o 150 mg è superiore a placebo (seguendo la randomizzazione iniziale) nei confronti della popolazione percentuale che raggiunge una risposta clinica rilevante (risposta ACR70 mantenuta per 6 mesi) ad un anno di trattamento • dimostrare che secukinumab 75 o 150 mg è superiore ad abatacept nei confronti della popolazione percentuale che raggiunge una risposta ACR20 a 24 settimane • dimostrare che a 24 settimane di trattamento, secukinumab 75 o 150 mg è in grado di apportare un miglioramento superiore ad abatacept rispetto al basale sulla base del questionario HAQ-DI • Per favore ved. protoc.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or non-pregnant, non-lactating female patients - Presence of rheumatoid arthritis classified by ACR 2010 revised criteria for at least 3 months before screening - At Baseline : disease activity criteria defined by ≥ 6 tender joints out of 68 and ≥ 6 swollen joints out of 66 WITH at least 1 of the following at screening: Anti-CCP antibodies positive OR Rheumatoid Factor positive AND WITH at least 1 of the following at screening: hsCRP ≥ 10mg/L ESR ≥ 28 mm/1st hr - Patients must have been taking at least one anti-TNFα agents given at an approved dose for at least 3 months before randomization and have experienced an inadequate response to treatment or have been intolerant to at least one administration of an anti-TNFα agent - Patients must be taking Methotrexate or any other DMARD (but not more than 1 DMARD) for at least 3 months before randomization and have to be on a stable dose at least 4 weeks before randomization (7,5 to 25mg/week for Methotrexate or other DMARD at maximum tolerated dose) Other protocol-defined inclusion criteria may apply.

• 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-TNF-α (quale etanercept, adalimumab, infliximab, certolizumab o golimumab) a dose appropriata per almeno 3 mesi prima della randomizzazione, con una risposta terapeutica inadeguata o un’intolleranza ad almeno una somministrazione • Trattamento con MTX o altro farmaco DMARD (non più di uno) per almeno 3 mesi prima della randomizzazione, con una dose stabile mantenuta per almeno 4 settimane prima della randomizzazione (MTX range da 7.5 a 25 mg/settimana, o DMARD alla dose massima tollerata)

E.4

Principal exclusion criteria

- Chest x-ray with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician - Rheumatoid arthritis patients functional status class IV according to the ACR 1991 revised criteria - Patients who have ever received biologic immunomodulating agents except for those targeting TNFα - Previous treatment with any cell-depleting therapies Other protocol-defined exclusion criteria may apply.

• Evidenza all’indagine radiografica del torace effettuata entro 3 mesi dallo screening, e validata da personale qualificato, di infezioni attive o processi neoplastici • Diagnosi di AR con status funzionale di classe IV in accordo con i criteri revisionati ACR 1992 • Trattamento pregresso con agenti biologici immunomodulanti ad eccezione dei tarmaci mirati all’inibizione del TNF • Trattamento pregresso con terapie di deplezione cellulare quali, ma non solo, anti CD20, o farmaci in sperimentazione (CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19)

E.5 End points

E.5.1

Primary end point(s)

ACR 20

L’endpoint primario di efficacia del presente studio è il raggiungimento dell’ACR20 alla settimana 24.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

settimana 24

E.5.2

Secondary end point(s)

HAQ-DI, major clinical response

HAQ-DI, risposta clinica principale

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 24 and 1 year

Settimana 24 e 1 anno

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

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity, Serum biomarkers analysis

immunogenicità, biomarkers

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

Brazil

Canada

Colombia

Mexico

Russian Federation

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 : 02/08/2013

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:

439

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

109

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

263

F.4.2.2

In the whole clinical trial

548

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

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

2011-06-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-06-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-02-03

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