Clinical Trials Register

Summary
EudraCT Number:	2012-000046-35
Sponsor's Protocol Code Number:	CAIN457F2310
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-26
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

Spain - AEMPS

A.2

EudraCT number

2012-000046-35

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled phase III multicenter study of subcutaneous secukinumab in prefilled syringes to demonstrate the efficacy at 16 weeks and to assess the long term efficacy, safety and tolerability up to 5 years in patients with active Ankylosing Spondylitis

Estudio de fase III, multicéntrico, aleatorizado, doble ciego, controlado con placebo de secukinumab subcutáneo en jeringas precargadas para demostrar la eficacia a las 16 semanas y evaluar la eficacia, seguridad y tolerabilidad a largo plazo, hasta 5 años, en pacientes con Espondilitis Anquilosante activa

A.3.1

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

Efficacy at 16 Weeks and Long Term Efficacy, Safety and Tolerability up to 5 years of Secukinumab (AIN457) in Patients With Active Ankylosing Spondylitis (AS)

Estudio de evaluación de eficacia a las 16 semanas y de eficacia, seguridad y tolerabilidad a largo plazo, hasta 5 años, de Secukinumab (AIN457) en pacientes con Espondilitis Anquilosante activa (EA)

A.4.1

Sponsor's protocol code number

CAIN457F2310

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 Farmacéutica, S.A.
B.1.3.4	Country	Spain
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 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 Farmacéutica, S.A.
B.5.2	Functional name of contact point	Inma Bosch
B.5.3	Address:
B.5.3.1	Street Address	Gran Vía Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34933064342
B.5.5	Fax number	+34933064290
B.5.6	E-mail	eecc.novartis@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 in pre-filled syringe
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	AIN457
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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 in pre-filled syringe
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 in pre-filled syringe
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

Espondilits Anquilosante

E.1.1.1

Medical condition in easily understood language

Bechterev syndrome, Marie-Strümpell disease

Síndrome de Bechterev, enfermedad de 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	15.0
E.1.2	Level	LLT
E.1.2	Classification code	10002557
E.1.2	Term	Ankylosing spondylitis and other inflammatory spondylopathies
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 ASAS 20 (Assessment of SpondyloArthritis International Society criteria) response at week 16 in subgroup of patients who are TNF? inhibitor naïve compared to placebo

Medir la proporción de sujetos que alcanzan una respuesta ASAS 20 (Criterios de la Assessment of SpondyloArthritis International Society) een la semana 16 en el subgrupo de sujetos que no han recibido tratamiento previo con un inhibidor del TNF?.

E.2.2

Secondary objectives of the trial

1) Measure the proportion of subjects achieving an ASAS 20 response in the whole study population compared to placebo at week 16

2) Measure the proportion of subjects achieving an ASAS 40 response at week 16 in subgroup of patients who are TNF? inhibitor naïve compared to placebo

3) Measure the proportion of subjects achieving an ASAS 40 response in the whole study population compared to placebo at week 16

1. Demostrar que la eficacia de al menos una pauta posológica de secukinumab (75 mg s.c. o 150 mg s.c.) en la semana 16 es superior a la de placebo en sujetos con EA activa basándose en la proporción de sujetos que alcanzan una respuesta ASAS 20 en toda la población del estudio.
2. Demostrar que la eficacia de al menos una pauta posológica de secukinumab (75 mg s.c. o 150 mg s.c.) en la semana 16 es superior a la de placebo en sujetos con EA activa basándose en la proporción de sujetos que alcanzan una respuesta ASAS 40 en sujetos que no han recibido tratamiento previo con un inhibidor del TNF?.
3. Demostrar que la eficacia de al menos una pauta posológica de secukinumab (75 mg s.c. o 150 mg s.c.) en la semana 16 es superior a la de placebo en sujetos con EA activa basándose en la proporción de sujetos que alcanzan una respuesta ASAS 40 en toda la población del estudio.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed.
2. Male or non-pregnant, non-lactating female patients at least 18 years of age.
3. Diagnosis of moderate to severe AS with prior documented radiologic evidence (x-ray or radiologist?s report) fulfilling the Modified New York criteria for AS (Appendix 3) with active AS assessed by BASDAI ?4 (0-10) and spinal pain as measured by VAS?4 cm at Baseline.
4. Patients should have been on NSAIDs at the highest recommended dose for at least 3 months prior to randomization with an inadequate response or failure to respond, or less
than 3 months if therapy had to be withdrawn due to intolerance, toxicity or contraindications.
5. Patients who are regularly taking NSAIDs (including COX-1 or COX-2 inhibitors) as part of their AS therapy are required to be on a stable dose for at least 2 weeks before randomisation.

Other protocol-defined inclusion criteria may apply.

1. El paciente debe ser capaz de entender y comunicarse con el investigador y cumplir con los requisitos del estudio y debe dar un consentimiento informado firmado y fechado por escrito antes de realizar cualquier evaluación del estudio.
2. Pacientes hombres o mujeres que no estén embarazadas ni en periodo de lactancia de al menos 18 años de edad.
3. Diagnósticos de EA de moderada grave con pruebas radiológicas documentadas previas (radiografía o informe del radiólogo) que cumplan los criterios de New York modificados para EA (Anexo 3) con EA activa evaluada según un BASDAI ?4 (0-10) y dolor en la columna vertebral medido según una EVA ?4 cm en la basal.
4. Pacientes que estén tomando AINE en la dosis más alta recomendada durante al menos 3 meses antes de la aleatorización con una respuesta inadecuada o que no respondan, o menos de 3 meses si el tratamiento se ha tenido que retirar debido a intolerancia, toxicidad o contraindicaciones.
5. Los pacientes que estén tomando regularmente AINE (incluidos los inhibidores de COX-1 o COX-2)como parte de su tratamiento para la EA es necesario que estén con una dosis estable durante al menos 2 semanas antes de la aleatorización

Otros criterios de inclusión definidos en el protocolo.

E.4

Principal exclusion criteria

1. Chest x-ray or MRI with evidence of ongoing infectious or malignant process, obtained within 3 months of screening and evaluated by a qualified physician.
2. Patients with total ankylosis of the spine.
3. Patients taking high potency opioid analgesics (e.g., methadone, hydromorphone, morphine)
4. Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor.

Other protocol-defined exclusion criteria may apply.

1. Radiografía de tórax o IRM que muestre infección o proceso maligno en curso, obtenida durante los 3 meses anteriores a la selección y evaluada por un médico cualificado.
2. Pacientes con anquilosis total de la columna vertebral.
3. Pacientes que estén tomando analgésicos opioides de elevada potencia (p. ej., metadona, hidromorfona o morfina).
4. Exposición previa a secukinumab u otro fármaco biológico que actúe directamente contra IL-17 o el receptor IL-17.

Otros criterios de exclusión definidos en el protocolo.

E.5 End points

E.5.1

Primary end point(s)

ASAS 20 in subgroup of patients who are TNF? inhibitor naïve

Respuesta ASAS 40 en sujetos que no han recibido tratamiento previo con un inhibidor del TNF?

E.5.1.1

Timepoint(s) of evaluation of this end point

week 16

Semana 16

E.5.2

Secondary end point(s)

1) ASAS 20 in whole study population

2) ASAS 40 in subgroup of patients who are TNF? inhibitor naïve

3) ASAS 40 in whole study population

1) ASAS 20 en la población total de estudio
2) ASAS 40 en un subgrupo de pacientes que no han recibido tratamiento previo con un inhibidor del TNF?
3) ASAS 40 en la población total de estudio

E.5.2.1

Timepoint(s) of evaluation of this end point

week 16

Semana 16

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

Austria

Canada

Czech Republic

Finland

Germany

Italy

Netherlands

Russian Federation

Singapore

Spain

Switzerland

United Kingdom

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

Ultmia visita del ultimo paciente

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:

210

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

130

F.4.2.2

In the whole clinical trial

222

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.

El investigador deberá proporcionar un seguimiento en la asistencia médica de todos los sujetos que se hayan retirado prematuramente del estudio, o deberá remitirlos para que reciban un tratamiento continuado apropiado. Este cuidado puede incluir iniciar otro tratamiento aparte del estudio considerado como adecuado por el investigador. Este tratamiento puede ser cualquier FAME no biológico. En caso de un tratamiento biológico, se recomienda un periodo de espera de 3 meses antes de iniciar el tra

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

2012-11-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-09-18

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