Clinical Trials Register

Summary
EudraCT Number:	2016-000972-91
Sponsor's Protocol Code Number:	CAIN457F3301
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:	2020-11-04
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

2016-000972-91

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled multicenter study of subcutaneous secukinumab to demonstrate efficacy in the treatment of enthesitis at the Achilles tendon up to 1 year in adult patients with active Psoriatic Arthritis (PsA) and axial Spondyloarthritis (axSpA) (ACHILLES)

Studio randomizzato, in doppio-cieco, controllato con placebo, multicentrico di secukinumab sottocute per dimostrare l’efficacia ad 1 anno nel trattamento dell’entesite al tendine di Achille nei pazienti adulti affetti da artrite psoriasica attiva (PsA) e spondiloartrite assiale (axSpA) (ACHILLES)

A.3.1

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

Study of efficacy and safety of secukinumab in Psoriatic Arthritis and axial Spondyloarthritis patients with
active enthesitis including one Achilles tendon site (ACHILLES)

Studo di efficacia e sicurezza nel trattamento dell’entesite al tendine di Achille nei pazienti adulti affetti da artrite psoriasica attiva (PsA) e spondiloartrite assiale (axSpA). (ACHILLES)

A.3.2

Name or abbreviated title of the trial where available

ACHILLES

A.4.1

Sponsor's protocol code number

CAIN457F3301

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	Novartis Farma Spa
B.5.2	Functional name of contact point	Drug Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Largo U. Boccioni, 1
B.5.3.2	Town/ city	Origgio - Milano
B.5.3.3	Post code	21040
B.5.3.4	Country	Italy
B.5.4	Telephone number	0296541
B.5.5	Fax number	029659066
B.5.6	E-mail	patrizia.ciavatta@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	Yes
D.2.1.1.1	Trade name	COSENTYX - 150 MG - SOLUZIONE INIETTABILE IN SIRINGA PRERIEMPITA -USO SOTTOCUTANEO - SIRINGA (VETRO) 1 ML (150MG/ML)- 1 SIRINGA PRERIEMPITA
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS EUROPHARM LTD
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.3.1	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	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)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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 - Axial spondyloarthritis

Artrite psoriasica attiva -Spondiloartrite assiale

E.1.1.1

Medical condition in easily understood language

Psoriatic arthritis-Axial spondyloarthritis

Artrite psoriasica attiva
Spondiloartrite assiale

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	10028395 - Musculoskeletal and connective tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10071400
E.1.2	Term	Axial spondyloarthritis
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

To demonstrate that the efficacy of secukinumab is superior to placebo based on the percentage of patients with resolution of Achilles tendon enthesitis as assessed by the respective subcomponent of the Leeds enthesitis index (LEI) at Week 24 in patients with active PsA and axSpA.

Dimostrare che l’efficacia di secukinumab è superiore al placebo in base alla percentuale di pazienti con risoluzione dell’entesite al tendine di Achille attraverso la valutazione del rispettivo sottocomponente dell’indice LEI (Leeds Enthesitis Index) alla settimana 24 nei pazienti affetti da PsA attiva e axSpA.

E.2.2

Secondary objectives of the trial

To demonstrate the efficacy of secukinumab at Week 24 is superior to placebo based on:
-mean change of heel pain measured on a 10-point NRS
-percentage of patients with an improvement of bone marrow edema as assessed by the respective subcomponent of the PsAMRIS in the affected foot at BSL
-percentage of patients with resolution of enthesitis as assessed by the LEI
-mean change in physician's and patient`s global assessment of disease activity
-mean change in physician's and patient`s global assessment of heel enthesiopathy activity
-change from BSL in SF-36 PCS or SF-36v2

To describe (after switching from placebo to secukinumab at Week 24) the increase in:
-percentage of patients with resolution of Achilles tendon enthesitis
-mean change of heel pain in patients

Overall safety and tolerability of secukinumab

Gli obiettivi secondari da valutare sono:
Dimostrare che l’efficacia di Secukinumab alla settimana 24 è superiore al placebo in base a:
• variazione media del dolore al tallone misurato su una scala di valutazione numerica a 10 punti (NRS).
• percentuale di pazienti con un miglioramento dell’edema midollare come valutato dal rispettivo sottocomponente del PsAMRIS score nel piede affetto al basale.
• percentuale di pazienti con risoluzione dell’entesite come valutato con indice LEI.
• variazione media nella valutazione globale del medico e del paziente dell’attività della malattia.
• variazione media nella valutazione globale del medico e del paziente dell’attività dell’entesite del tallone.
• cambiamento rispetto al basale in SF-36 PCS o di SF-36v2.
Descrivere dopo il passaggio da placebo a secukinumab alla settimana 24 l’aumento in:
• percentuale di pazienti con risoluzione dell’entesite del tendine di Achille.
• variazione media del dolore al tallone.
La sicurezza e tollerabilità

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Psoriatic arthritis patients must fulfill the following criteria:
Diagnosis of Psoriatic arthritis classified by Classification criteria for Psoriatic Arthritis (CASPAR criteria) with symptoms for at least 6 months and active Psoriatic arthritis as assessed by > 1 tender joints out of 78 and > 1 swollen joints out of 76 at Baseline (dactylitis of a digit counts as one joint each)
- Axial Spondyloarthritis patients must fulfill the following criteria:
Axial Spondyloarthritis as per the classification of the Assessment of Spondyloarthritis International Society axial Spondyloarthritis (ASAS) criteria with objective signs of inflammation at Screening (magnetic resonance imaging (MRI) with Sacroiliac joint inflammation or definite radiographic sacroilitis according to the modified New York (NY) criteria and/or abnormal high sensitivity C-Reactive Protein (hsCRP)) and active disease assessed by total Bath ankylosing spondylitis disease activity index (BASDAI) = 4 (0–10) at Baseline
- Diagnosis of Achilles tendon enthesitis according to swelling and tenderness at the insertional site of the Achilles tendon into the calcaneus
- Onset of heel pain = 1 month up to 5 years at Baseline
- Heel enthesitis that is magnetic resonance imaging (MRI)-positive according to the investigator`s judgement
- Patients who are Tumor necrosis factor (TNF) inhibitor-naive

Other protocol defined inclusion criteria may apply.

-Pazienti con PsA che soddisfano i seguenti:
• diagnosi secondo i criteri CASPAR con sintomi da almeno 6 mesi
• malattia attiva valutata al basale da un nr. di articolazioni dolenti >1 su 78 e un numero di tumefatte s >1 su 76
-Pazienti con axSpA che soddisfano i seguenti:
• diagnosi secondo i criteri ASAS con segni obiettivi di infiammazione allo screening (infiammazione all’articolazione sacroiliaca evidenziata con MRI o sacroileite definita radiograficamente in base ai criteri NY modificati e/o un valore di hsCRP > del limite superiore di normalità e
• malattia attiva valutata attraverso BASDAI totale = 4 (scala 0 – 10) al basale.
-Diagnosi di entesite del tendine di Achille in base al gonfiore e la dolorabilità al sito di inserzione del tendine di Achille al calcagno.
-Al basale dolore al tallone insorto da 1 mese fino a 5 anni prima
-Entesite al tallone positiva a MRI secondo il giudizio dello sperimentatore.
-Nessun precedente uso di anti-TNF alfa
Vedi Protocollo per ulteriori criteri di inclusione.

E.4

Principal exclusion criteria

- Chest X-ray or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process
- Previous exposure to secukinumab or other biologic drug directly targeting Interleukin (IL)-17 or Interleukin (IL)-17 receptor
- Ongoing use of psoriasis treatments / medications (e.g. topical corticosteroids, ultraviolet (UV) therapy) at randomization
- Patients who have previously been treated with Tumor necrosis factor (TNF) inhibitors (investigational or approved).
- Patients who have ever received biologic immunomodulating agents (investigational or approved)
- Pregnant or nursing (lactating) women
- History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection

Other protocol defined exclusion criteria may apply.

I pazienti che soddisfano uno qualsiasi dei seguenti criteri non sono eleggibili per l’inclusione in questo studio:
1. RX torace o MRI torace con evidenza di infezioni in corso o processo neoplastico.
2. Precedente assunzione di secukinumab o altri farmaci biologici mirati direttamente a IL-17 o a recettore dell’IL-17.
3. Uso concomitante di trattamenti/farmaci per la psoriasi alla randomizzazione (es. corticosteroidi topici, terapia UV).
4. Pazienti che sono stati precedentemente trattati con anti-TNF (sperimentale o approvato).
5. Pazienti che abbiamo ricevuto trattamento con agenti biologici immuonomodulanti (sperimentali o approvati).
6. Donne incinta o in allattamento
7. Storia di patologie infettive in corso, croniche o ricorrenti o evidenza di tubercolosi
Vedi Protocollo per ulteriori criteri di esclusione

E.5 End points

E.5.1

Primary end point(s)

Percentage of patients with resolution of Achilles tendon enthesitis

Percentuali di pazienti con risoluzione dell'entesite al tendine di Achille.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 week

Settimana 24

E.5.2

Secondary end point(s)

1) Heel pain 2) Percentage of patients with an improvement of bone marrow edema 3) Percentage of patients with resolution of enthesitis 4) Physician`s global assessment of disease activity 5) Patient`s global assessment of disease activity 6) Physician`s global assessment of heel enthesiopathy activity 7) Patient`s global assessment of heel enthesiopathy activity 8) Short Form-36 Physical Component Summary (SF-36 PCS) or Short Form-36 (SF-36) v2 9) Percentage of patients with resolution of Achilles tendon enthesitis after switching form placebo 10) Heel pain in patients after switching from placebo 11) Safety and tolerability

1)Dolore al Calcagno 2)Percentuale di pazienti con miglioramento dell’edema midollare 3) Percentuale di pazienti con risoluzione dell’entesite 4) valutazione globale dell’attività di malattia da parte del medico 5) valutazione globale dell’attiva di malattia da parte del paziente 6) valutazione globale dell’attività dell’entesite al tallone da parte del medico 7) ) valutazione globale dell’attività dell’entesite al tallone da parte del paziente 8) Short Form-36 Physical Component Summary (SF-36 PCS) or Short Form-36 (SF-36) v2 9) Percentuali di pazienti con risoluzione dell’entesite al tendine di Achille dopo passaggio da trattamento attivo al placebo 10)dolore al tallone nei pazienti dopo passaggio da trattamento attivo al placebo 11) sicurezza e tollerabilità.

E.5.2.1

Timepoint(s) of evaluation of this end point

1-8: Week 24 9 + 10: Week 52 11: BSL - Week 52

1-8 alla settimana 24
9-10 alla settimana 52
11 dal basale alla settimana 52

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

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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:

180

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

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

200

F.4.2.2

In the whole clinical trial

200

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 NSAID/DMARD. In case of a biologic treatment, a waiting period of 3 months before initiating the treatment is recommended.

Lo Sperimentatore deve fornire cure mediche di follow-up per tutti i pazienti che sono prematuramente ritirati dallo studio o deve indirizzarli alle cure mediche appropriate. Questo può includere iniziare un altro trattamento al di fuori dello studio, come ritenuto opportuno dallo sperimentatore . Questo trattamento può essere qualsiasi tipo di FANS non-biologica/DMARD. In caso di trattamento biologico, si raccomanda un periodo di attesa di 3 mesi prima di iniziare il 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

2016-10-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-10-19

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

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