Clinical Trials Register

Summary
EudraCT Number:	2013-005575-41
Sponsor's Protocol Code Number:	CAIN457F2320
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:	2016-03-11
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

2013-005575-41

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled, phase III multicenter study of subcutaneous secukinumab (150 mg) with and without a subcutaneous loading regimen to assess efficacy, safety, and tolerability up to 2 years in patients with active ankylosing spondylitis

A.3.1

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

16-week efficacy and 2-year safety, tolerability and efficacy of secukinumab in participants with active ankylosing spondylitis

Efficacia, sicurezza e tollerabilità di un regime con carico vs. un regime senza carico di secukinumab sottocutaneo a confronto con placebo fino a 2 anni in pazienti con spondilite anchilosante (Ankylosing Spondylitis - AS) attiva

A.3.2

Name or abbreviated title of the trial where available

MEASURE 4

A.4.1

Sponsor's protocol code number

CAIN457F2320

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 S.P.A.
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	Azienda Farmaceutica: Novartis Pharma Services AG
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 S.p.A.
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	21010
B.5.3.4	Country	Italy
B.5.4	Telephone number	0296541
B.5.5	Fax number	029659066
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	AIN457
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.3.9.3	Other descriptive name	SECUKINUMAB
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	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
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 in pre-filled injector
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

Ankylosing Spondylitis

spondilite anchilosante

E.1.1.1

Medical condition in easily understood language

Bechterev syndrom, Marie-Strümpell disea

morbo di Bechterev, Malattia di Marie-Strümpell

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	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10002555
E.1.2	Term	Ankles swollen
E.1.2	System Organ Class	100000004859

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 demonstrate that the efficacy of secukinumab 150 mg at Week 16 with or without a loading regimen is superior to placebo based on the
proportion of subjects achieving an ASAS20 (Assessment of SpondyloArthritis International Society criteria) response.

Dimostrare che l’efficacia di secukinumab 150 mg con o senza regime di carico, alla Settimana 16, sia superiore a placebo in base alla proporzione di soggetti che raggiungono una risposta ASAS20 (criteri della Assessment of SpondyloArthritis International Society).

E.2.2

Secondary objectives of the trial

To demonstrate that the efficacy of secukinumab 150 mg s.c., with or without loading, at Week 16 is superior to placebo based on
•the proportion of subjects achieving an ASAS40 response
•the change from baseline of high sensitivity C-Reactive Protein (hsCRP)
•the proportion of patients meeting the ASAS 5/6 response criteria
•the change from baseline in total Bath Ankylosing Spondylitis Disease Activity (BASDAI)
•the change from baseline in Short Form-36 Physical Component Summary (SF-36 PCS)
•the change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL)
-To demonstrate that the efficacy of secukinumab 150 mg s.c., with or without loading, at
Week 4 is superior to placebo based on:
•the proportion of subjects achieving an ASAS20 response
•the proportion of subjects achieving an ASAS40 response
- Overall safety and tolerability of secukinumab

Dimostrare che l’efficacia di secukinumab 150 mg s.c., con o senza carico, alla Settimana 16 sia superiore a placebo in base: - alla proporzione di pazienti che raggiungono una risposta ASAS40. - alla variazione rispetto al basale della proteina C-reattiva ad alta sensibilità (High Sensitivity C-Reactive Protein – hsCRP). -alla proporzione di pazienti che soddisfa i criteri di risposta ASAS 5/6. - alla variazione rispetto al basale nell’indice totale BASDAI (Bath Ankylosing Spondylitis Disease Activity Index). - alla variazione rispetto al basale nello Short Form-36 Physical Component Summary (SF-36 PCS). - alla variazione rispetto al basale
dell’AnkylosingSpondylitis Quality of Life (ASQoL). Dimostrare che l’efficacia di secukinumab 150 mg s.c., con o
senza carico, alla Settimana 4, sia superiore a placebo in base: - alla proporzione di pazienti che raggiunge una risposta ASAS20, - alla
proporzione di soggetti che raggiunge una risposta ASAS40. Sicurezza e tollerabilità complessive

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

Pharmacogenetics
Exploratory pharmacogenetics research studies are planned as a part of this study with the
objectives of identifying inherited genetic factors which may (1) be related to AS, (2) predict
response to treatment with secukinumab, (3) predict relative susceptibility to drug-drug
interactions, or (4) predict genetic predisposition to side effects.
v00 del 23.10.2014

Indagine di Farmacogenetica
Individuare i fattori genetici ereditari che possono (1) essere legati alla AS, (2) prevedere la risposta al trattamento con secukinumab, (3) prevedere la suscettibilità all'interazione farmaco-farmaco, o (4) prevedere la predisposizione genetica agli effetti collaterali.
basata su protocollo originale v00 del 23.10.2014

E.3

Principal inclusion criteria

- Moderate to severe AS
- Prior radiographic evidence according to the Modified NY Criteria (1984)
- Inadequate response to NSAIDs
Other protocol-definied inclusion criteria may apply.

Pazienti uomini o donne non in gravidanza o in allattamento di almeno 18 anni di età.
Diagnosi di AS da moderata a severa con pregressa evidenza radiologica documentata (radiografia o referto del radiologo) che soddisfano i criteri “Modified New York criteria” per AS
I pazienti devono essere stati in trattamento con FANS alla dose massima raccomandata per almeno 3 mesi con una risposta non adeguata o per meno di 3 mesi se il trattamento è stato sospeso per intolleranza, tossicità o controindicazioni.
Ai pazienti che assumono regolarmente FANS come parte della loro terapia per AS si richiede di essere in trattamento a dose stabile da almeno 2 settimane prima della randomizzazione.
I pazienti che sono stati in trattamento con un inibitore di TNFα (non più di uno) devono aver manifestato una risposta inadeguata o devono essere risultati intolleranti.

E.4

Principal exclusion criteria

- Pregnancy or lactation
- On-going infectious or malignant process on a chest X-ray or MRI
- Previous exposure to IL-17 or IL-17R targeting therapies
- Previous exposure to any biological immunomodulating agent
excluding TNF antagonists
- Previous cell depleting therapy
Other protocol-definied exclusion criteria may apply.

I pazienti che soddisfano uno qualsiasi dei seguenti criteri non sono eleggibili per l’inclusione in questo studio:
Radiografia toracica o risonanza magnetica con evidenza di processo infettivo o maligno in corso.
Precedente esposizione a secukinumab o a qualsiasi altro farmaco biologico avente come target diretto IL-17 o il recettore di IL-17.
Pazienti precedentemente trattati con qualsiasi agente immunomodulatore biologico, ad eccezione degli agenti che hanno come bersaglio TNFα.
Pazienti che hanno assunto più di un agente anti-TNFα.
Pregresso trattamento con qualsiasi terapia di deplezione cellulare.

E.5 End points

E.5.1

Primary end point(s)

Assessment of Spondyloarthritis International Society criteria, ASAS 20

Valutazione secondo i ciriteri della SpondyloArthritis International Society (ASAS).

E.5.1.1

Timepoint(s) of evaluation of this end point

16 weeks

16 settimane

E.5.2

Secondary end point(s)

- ASAS 40 response (a) - Serum hsCRP (a) - ASAS 5/6 response (a) - Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (a) - Short Form-36 Physical Compenent Summary (SF-36 PCS) health survey (a) - Ankylosing Spondylitis Quality of Life (ASQoL) (a) - Overall safety and tolerability (b)

- risposta ASAS40 (a) - hsCRP sierica (a) - risposta ASA5/6 (a) - BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) (a) - Short Form-36 Physical Component Summary (SF-36 PCS) (a) - AnkylosingSpondylitis Quality of Life (ASQoL) (a) - sicurezza e tollerabilità (b)

E.5.2.1

Timepoint(s) of evaluation of this end point

(a) 16 weeks (b) 112 weeks

(a) 16 settimane (b) 112 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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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

Australia

Austria

Bulgaria

Canada

Czech Republic

Denmark

Finland

Germany

Greece

Italy

Mexico

Netherlands

Norway

Poland

E.8.7

Trial has a data monitoring committee

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

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.1.1.1

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:

304

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

297

F.4.2.2

In the whole clinical trial

324

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 are prematurely withdrawn from 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.

L'investigatore deve fornire il follow-up delle cure mediche per tutti i soggetti che abbandonano prematuramente lo studio,o fornire riferimenti per
adeguate cure in corso. Questa cura può rappresentare un altro trat. al di fuori dello studio, come ritenuto opportuno dal
investigatore. Questo trat. può essere qualsiasi DMARD non biologico. Nel caso venga scelto un trat. biologico, si raccomanda di eseguire un periodo di sospensione dei trat. di 3 mesi prima di iniziare il nuovo trattamento.

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

2015-02-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-05

P. End of Trial
P.	End of Trial Status	Completed

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