Clinical Trials Register

Summary
EudraCT Number:	2015-002394-38
Sponsor's Protocol Code Number:	CAIN457F2354
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:	2021-09-10
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

2015-002394-38

A.3

Full title of the trial

A 52-week, multicenter study to assess the time course of response to secukinumab on joint inflammation using Power Doppler ultrasonography in patients with active psoriatic arthritis

A.3.1

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

Study of application of Power Doppler ultrasonography (PDUS) to measure response to secukinumab treatment in patients with active psoriatic arthritis (PsA)

Studio multicentrico di 52 settimane volto a valutare, mediante ecografia
Power Doppler, l'andamento temporale della risposta a secukinumab
sull'infiammazione articolare in pazienti affetti da artrite psoriasica attiva.

A.3.2

Name or abbreviated title of the trial where available

Study of application of Power Doppler ultrasonography (PDUS) to measure response to secukinumab trea

Studio sull'impiego dell'ecografia Power Doppler (PDUS) per la misurazione della risposta al trattam

A.4.1

Sponsor's protocol code number

CAIN457F2354

A.5.4

Other Identifiers

Name:

AIN457/Secukinumab

Number:

CAIN457F2354

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 PHARMA SERVICES AG
B.1.3.4	Country	Switzerland
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 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	TFS UK Limited
B.5.2	Functional name of contact point	Clinical Operation
B.5.3	Address:
B.5.3.1	Street Address	54A Cowley Mill Road
B.5.3.2	Town/ city	Uxbridge, Middlesex,
B.5.3.3	Post code	UB8 2QE – UK
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00442034054908
B.5.5	Fax number	00442034054908
B.5.6	E-mail	jody.whitehead@tfscro.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	Yes
D.2.1.1.1	Trade name	COSENTYX
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.11 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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Psoriatic Arthritis

Artrite psoriasica

E.1.1.1

Medical condition in easily understood language

Psoriatic Arthritis

Artrite psoriasica

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10037160
E.1.2	Term	Psoriatic arthritis
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 there is a difference between secukinumab and placebo in terms of joint synovitis response over 12 weeks as measured by the PDUS Global OMERACT-EULAR Synovitis Score (GLOESS) of the affected joints (out of 48 joints) in PsA patients with an inadequate response (IR) to non biologic DMARDs.

Dimostrare che esiste una differenza tra secukinumab e il placebo in
termini di risposta dell'artrosinovite nell'arco di 12 settimane, sulla
base del punteggio OMERACT-EULAR globale per la sinovite
ottenuto mediante PDUS (GLOESS) delle articolazioni colpite (su 48
articolazioni) in pazienti affetti da APs che presentano una risposta
inadeguata a DMARD non biologici

E.2.2

Secondary objectives of the trial

Key secondary objectives:
•To demonstrate that the efficacy of secukinumab at Week 12 is superior to placebo based on the proportion of patients achieving:
- an ACR 20 response
- an ACR 50 response
•To demonstrate that the clinical response of secukinumab at Week 12 is superior to placebo based on the change in SPARCC enthesitis index from Baseline to Week 12.

Obiettivi secondari chiave:
Dimostrare che l'efficacia di secukinumab alla Settimana 12 è superiore a quella del placebo, sulla base della percentuale di pazienti che raggiungono: - una risposta ACR pari a 20
- una risposta ACR pari a 50
• Dimostrare che la risposta clinica di secukinumab alla Settimana 12 è superiore a quella del placebo, sulla base della variazione, dal
Basale alla Settimana 12, dell'indice SPARCC (Spondyloarthritis Research Consortium of Canada) per l'entesite.

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

Other types of substudies
Specify title, date and version of each substudy with relative objectives: Optional PDUS Sub-study 2015-11-20
• Explore early signs of response in the skin and nails of patients with concomitant moderate-to-severe psoriasis or nail psoriasis, based on the change from Baseline of Power Doppler signal, at each evaluation time, using a semi quantitative score (0 = absence or up to 2 spots, 1 = < 25% vascularization of the plaque/nail bed, 2 = > 25% and < 50% vascularization of the plaque/nail bed, 3 = > 50% vascularization of the plaque/nail bed).
• Explore time course of response to secukinumab on PDUS dactylitis in patients with concomitant dactylitis will be evaluated based on the change from Baseline at each evaluation time of the elementary components involved: synovitis (using the OMERACT-EULAR scoring system), flexor tendon tenosynovitis (using the OMERACT scoring system for evaluating the presence or absence of tenosynovitis) (Naredo et al 2013), and subcutaneous involvement (using the decrease of the thickness and the disappearance of the power Doppler signal if present (Gutierrez et al 2012)).
• Explore the rate of response with secukinumab between Week 4 and Week 12 assessed by clinical evaluation using dactylitis count by Leeds Dactylitis Index (LDI) and by the PDUS of dactylitis.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Sottostudio PDUS opzionale data 20-11-2015
Esplora i primi segni di risposta nella pelle e le unghie dei pazienti con concomitante moderata-grave della psoriasi o psoriasi unghiale, sulla base del cambiamento dal basale del segnale power Doppler, in ogni tempo di valutazione, con un punteggio quantitativo (0 = assenza o fino a 2 punti, 1 = <25% vascolarizzazione del letto unghiale 2 => 25% e <50% vascolarizzazione del letto unghiale, 3 => 50% vascolarizzazione del letto unghiale).
• Esplora andamento nel tempo della risposta alla secukinumab su PDUS dactilite nei pazienti con dactilite concomitante saranno valutati sulla base del cambiamento dal basale ad ogni tempo di valutazione dei componenti elementari coinvolte: sinovite (utilizzando il sistema di punteggio OMERACT-EULAR), tendine flessore tenosinovite ( utilizzando il sistema di punteggio OMERACT per valutare la presenza o l'assenza di tenosinovite) (Nardo et al 2013), e il coinvolgimento sottocutanea (con la diminuzione dello spessore e la scomparsa del segnale power Doppler se presente (Gutierrez et al 2012)).
• Esplora il tasso di risposta con secukinumab tra Settimana 4 e la settimana 12 valutati da una valutazione clinica utilizzando conteggio dactilite da Leeds Dactylitis Index (LDI) e dalla PDUS di dactilite.

E.3

Principal inclusion criteria

Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1. Patient must be able to understand and communicate with the Investigator and comply with the requirements of the study and must provide written, signed and dated informed consent before any study assessment is performed.
2. Male or female patients at least 18 years of age.
3. Diagnosis of PsA as per CASPAR with active PsA for at least 6 months and a TJC = 3 of 78 and SJC = 3 of 76 at Baseline.
4. Patients must have a total synovitis PDUS score = 2 and inflammation related to PD signal = 2 for at least 2 (affected joints as observed via PDUS) of 48 joints at the Screening visit and at the Baseline visit (before injection).
5. At least 1 clinically-involved enthesitis site at Screening and at the Baseline visit (before injection) defined by SPARCC index different from 0.
6. Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) negative at Screening.
7. Patients with PsA who are taking NSAIDs should be on a stable dose for at least 2 weeks prior to enrollment and remain on a stable dose throughout the 24-week study period.
8. Patients with PsA who are taking steroids must have received steroids at least 3 months prior to the Baseline visit and be on a stable dose of = 10 mg equivalent prednisone for at least 4 weeks prior to Baseline visit and remain on a stable dose throughout the 24-week study period unless tolerance issues.
9. Patients with PsA who are taking MTX or DMARDs must have received them at least 3 months prior to Baseline visit and be on a stable dose of = 25 mg/week of MTX or stable standard doses of other DMARD(s) (according to the Investigator’s judgment) for at least 4 weeks prior to the Baseline visit and remain on a stable dose throughout the 24-week study period.

Ai fini dell'inclusione nello studio, i pazienti devono soddisfare tutti i seguenti criteri:
1. Paziente in grado di comprendere e parlare con lo sperimentatore e di ottemperare ai requisiti dello studio. Fornitura del consenso informato scritto firmato e datato prima dell'esecuzione di qualsiasi valutazione dello studio.
2. Pazienti di sesso maschile o femminile di età =18 anni.
3. Diagnosi di APs secondo i criteri CASPAR con APs attiva da almeno 6 mesi e TJC e SJC al Basale pari a =3 di 78 e =3 di 76 rispettivamente.
4. Pazienti con punteggio totale per la sinovite alla PDUS =2 e infiammazione relativa al segnale PD =2 per almeno 2 articolazioni su 48 (articolazioni interessate come osservato mediante PDSU) alla Visita di screening e alla Visita basale (prima dell'iniezione).
5. Almeno 1 sede clinicamente interessata da entesite allo Screening e alla Visita basale (prima dell'iniezione), definita mediante un indice SPARCC diverso da 0.
6. Risultato negativo allo Screening per il fattore reumatoide e gli anticorpi anti-peptide ciclico citrullinato (anti-CCP).
7. I pazienti con APs in trattamento con FANS devono aver assunto una dose stabile per almeno 2 settimane prima dell'arruolamento e continuare ad assumere una dose stabile per l'intero periodo di studio di 24 settimane.
8. I pazienti con APs in trattamento con steroidi devono aver assunto steroidi per almeno 3 mesi prima della Visita basale e aver assunto una dose stabile =10 mg di prednisone equivalente per almeno 4 settimane prima della Visita basale, nonché continuare ad assumere una dose stabile per l'intero periodo di studio di 24 settimane, eccetto in caso di problemi di tolleranza.
9. I pazienti con APs in trattamento con metotrexato o DMARD devono averli assunti per almeno 3 mesi prima della Visita basale, aver assunto una dose stabile =25 mg/settimana di metotrexato o dosi standard stabili di un altro DMARD (secondo il giudizio dello sperimentatore) per almeno 4 settimane prima della visita basale, e continuare ad assumere una dose stabile per l'intero periodo di studio di 24 settimane.

E.4

Principal exclusion criteria

-Chest X-ray or chest MRI with evidence of ongoing infectious or
malignant process obtained within 3 months prior to Screening and
evaluated by a qualified physician.
-Previous exposure to secukinumab or other biologic drug directly
targeting IL-17 or IL-17 receptor.
-Any change in the dose of oral corticosteroids in the last 4 weeks prior
to the Baseline visit or use of i.v. intramuscular or intra-articular
corticosteroid during the last 4 weeks prior to the enrollment visit.
-Patients who have previously been treated with TNFa inhibitors
(investigational or approved).
-History of hypersensitivity to the study drug or its excipients or to drugs
of similar classes.
-Previous treatment with any cell-depleting therapies including but not
limited to anti CD20 investigational agents (e.g. CAMPATH, anti-CD4,
anti-CD5, anti-CD3, anti CD19).
-Prohibited psoriasis treatments/medications with topical
corticosteroids in the last 4 weeks prior to randomization.
-Pregnant or nursing (lactating) women.
Other protocol defined exclusion criteria may apply.

Radiografia o RMI toracica con evidenza di processo infettivo o maligno in corso ottenute nei 3 mesi precedenti allo Screening e valutate da un medico qualificato.
Precedente esposizione a secukinumab o ad un altro farmaco biologico mirato direttamente all'interleuchina 17 (IL-17) o al recettore dell'IL-17.
Qualsiasi cambiamento della dose di corticosteroidi orali nelle 4 settimane precedenti alla Visita basale oppure uso di corticosteroidi per via e.v. intramuscolare o intra-articolare nelle 4 settimane precedenti alla visita di arruolamento.
Pazienti trattati in precedenza con inibitori del TNFa (in fase di sperimentazione o approvati).
Anamnesi di ipersensibilità al farmaco in studio o ai suoi eccipienti oppure a farmaci di classi simili.
Precedente trattamento con qualsiasi terapia di deplezione delle cellule, inclusi, senza pretesa di esaustività, gli agenti sperimentali anti-CD20 (ad es. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19).
Farmaci/trattamenti per la psoriasi vietati con corticosteroidi topici nelle 4 settimane precedenti alla randomizzazione (vedasi la Sezione 5.5.8).
Altri criteri di esclusione definiti nel protocollo, si possono applicare

E.5 End points

E.5.1

Primary end point(s)

Difference between secukinumab and placebo in terms of joint synovitis

Differenza tra secukinumab e placebo in termini di sinovite articolare

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks

12 settimane

E.5.2

Secondary end point(s)

- American College of Rheumatology (ACR)-20 - ACR-50 - Spondyloarthritis Research Consortium of Canada(SPARCC)

- American College of Reumatologia (ACR) -20
- ACR-50
- Consorzio di Ricerca spondiloartrite del Canada (SPARCC)

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline to Week 12

basale a 12 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

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

Information not present in EudraCT

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

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:

193

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

165

F.4.2.2

In the whole clinical trial

218

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 patients 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.

nessuno

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

2016-07-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-19

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

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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