Clinical Trials Register

Summary
EudraCT Number:	2013-004867-29
Sponsor's Protocol Code Number:	CACZ885G2306
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-09-23
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

Netherlands - Competent Authority

A.2

EudraCT number

2013-004867-29

A.3

Full title of the trial

An open-label canakinumab (ACZ885) dose reduction or dose interval prolongation efficacy and safety study in patients with Systemic Juvenile Idiopathic Arthritis (SJIA)

Een open-label studie met canakinumab (ACZ885) bij patiënten met systemische juveniele idiopatische artritis (SJIA) waarbij effectiviteit werkzaamheid en veiligheid wordt onderzocht bij verlaging van de dosering en verlenging van het dosisinterval

A.3.1

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

Study of efficacy and safety of dose reduction or dose interval prolongation of canakinumab in patients with SJIA

Een studie naar werkzaamheid en veiligheid van canakinumab bij patienten met SJIA wanneer de dosis wordt verlaagd of dosisinterval wordt verlengd

A.3.2

Name or abbreviated title of the trial where available

CACZ885G2306

A.4.1

Sponsor's protocol code number

CACZ885G2306

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02296424

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 Pharma Services AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Lichtstrasse 35
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+44613241111
B.5.5	Fax number	+44613248001
B.5.6	E-mail	clinicaltrial.enquiries@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	canakinumab
D.3.2	Product code	ACZ885
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	CANAKINUMAB
D.3.9.1	CAS number	914613-48-2
D.3.9.2	Current sponsor code	ACZ885
D.3.9.4	EV Substance Code	SUB30137
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Active systemic manifestations of Systemic Juvenile Idiopathic Arthritis (SJIA)

Actief manifesterende systemische juveniele idiopatische artritis (SJIA)

E.1.1.1

Medical condition in easily understood language

SJIA is a serious, potentially disabling form of arthritis that causes swelling in the joints and inflammation in other parts of the body.

SJIA is een ernstige, mogelijk invaliderende vorm van artritis dat zwelling van de gewrichten en ontsteking in andere delen van het lichaam geeft.

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	19.1
E.1.2	Level	PT
E.1.2	Classification code	10059176
E.1.2	Term	Juvenile idiopathic arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate if the proportion of patients in clinical remission on canakinumab 4mg/kg (+/- concomitant NSAID only) who are able to remain on a reduced canakinumab dose (2mg/kg every 4 weeks) or prolonged canakinumab dose interval (4mg/kg every 8 weeks) for at least 24 consecutive weeks is at least 40% in either treatment
arm (Part II).

Evalueren of het aantal met canakinumab 4 mg/kg behandelde patiënten in klinsiche remissie (+/- NSAID alleen als co-medicatie) dat in staat is op een lagere dosis canakinumab (2 mg/kg om de 4 weken) of bij een verlengd canakinumab dosisinterval (4 mg/kg elke 8 weken) gedurende ten minste 24 opeenvolgende weken in klinische remissie te blijven, ten minste 40% is in beide behandelgroepen (deel II).

E.2.2

Secondary objectives of the trial

To assess the long-term safety and tolerability of canakinumab
(Parts I and II).

Beoordelen van de veiligheid en verdraagbaarheid van canakinumab op lange termijn (deel I en II).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion Criteria- Cohort 1:
• Parent’s or legal guardian’s written informed consent and child’s assent, if appropriate, or patient’s written informed consent for ≥18 years of age
• Patients who are receiving canakinumab treatment (4 mg/kg every 4 weeks) for SJIA and have inactive disease at the last visit in Study CACZ885G2301E1 .

Inclusion Criteria- Cohort 2:
• Parent’s or legal guardian’s written informed consent and child’s assent, if appropriate, or patient’s written informed consent for ≥ 18 years of age must be obtained before any study related activity or assessment is performed.
• Male and female patients aged ≥ 2 to < 20 years at the time of the screening visit
• Confirmed diagnosis of SJIA as per ILAR definition that must have occurred at least 2 months prior to enrollment with an onset of disease < 16 years of age:
• Arthritis in one or more joints, with or preceded by fever of at least 2 weeks duration that is documented to be daily/quotidian for at least 3 days and accompanied by one or more of the following:
- Evanescent non-fixed erythematous rash
- Generalized lymph node enlargement
- Hepatomegaly and/ or splenomegaly
- Serositis
• Active SJIA at the time of baseline visit defined as having 2 or more of the following:
- Documented spiking, intermittent fever (body temperature > 38°C) for at least 1 day during the screening period and within 1 week before first canakinumab dose,
- At least 2 joints with active arthritis (using ACR definition of active joint)
- C-reactive protein (CRP) > 30 mg/L (normal range < 10 mg/L)
- Rash
- Serositis,
- Lymphadenopathy,
- Hepatosplenomegaly
• Patient’s willingness to discontinue anakinra, rilonacept, tocilizumab, abatacept or other experimental or approved drug under close monitoring (Please refer to Cohort 2 exclusion criteria #16 for washout period.)
• Negative QuantiFERON (QF) test (or, if required by local guidelines, negative Purified Protein Derivative [PPD] test [< 5 mm induration]) at screening or within 1 month prior to the screening visit.

Inclusie criteria - Cohort 1:
• Schriftelijk toestemming ouder/voogd en de instemming van het kind, indien van toepassing, of schriftelijk toestemming patiënt van ≥ 18 jaar
• Patiënten behandeld met canakinumab (4 mg/kg om de 4 weken) voor SJIA en inactieve ziekte op het laatste bezoek in studie CACZ885G2301E1.

Inclusie criteria- Cohort 2:
• Schriftelijk toestemming ouder/voogd en de instemming van het kind, indien van toepassing, of schriftelijk toestemming patiënt van ≥ 18 jaar
• Mannen en vrouwen van 2 tot 20 jaar op het moment van screening
• Bevestigde diagnose van SJIA als per ILAR definitie van ten minste 2 maanden voorafgaand aan de screening en startdatum van deze ziekte voor de leeftijd van 16 jaar
• Artritis in een of meer gewrichten, met koorts of voorafgegaand door koorts, minstens 2 weken lang en ten minste 3 dagen lang dagelijks vergezeld met een of meer van de volgende:
- Voorbijgaande en afwrijfbare erythemateuze huiduitslag
- Vergrote lymfeklieren
- Hepatomegalie en / of splenomegalie
- Serositis
• Actieve SJIA op moment van baseline gedefinieerd als hebbende 2 of meer van de volgende:
- Gedocumenteerde stekelige, intermitterende koorts (lichaamstemperatuur> 38 ° C) gedurende ten minste 1 dag tijdens de screening en binnen 1 week voor de eerste canakinumab dosis
- Ten minste 2 gewrichten met actieve artritis (volgens ACR definitie)
- C-reactief proteïne (CRP) > 30 mg/ L (normaalwaarde <10 mg / L)
- Huiduitslag
- Serositis
- Lymphadenopathie
- Hepatosplenomegalie
• De bereidheid van de patiënt om evt. behandeling met anakinra, rilonacept, tocilizumab, abatacept of andere experimentele of geregistreerde geneesmiddelen te stoppen
• Negatieve QuantiFERON (QF)-test of een negatieve Mantoux huidtest (<5 mm induratie) op moment van screening of binnen 1 maand voorafgaand aan de screening

E.4

Principal exclusion criteria

Exclusion criteria – Cohort 1 and 2:
• Pregnant or nursing (lactating) female patients, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Female patients of child-bearing potential, defined as all females physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. Effective contraception methods defined in protocol.
• With active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infection.
• History or evidence of tuberculosis (TB) (active or latent) infection or one of the risk factors for tuberculosis (TB) as defined in protocol.
• With underlying metabolic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and €/ or places the patient at unacceptable risk for participation in an immunomodulatory therapy. In particular, clinical evidence or history of multiple sclerosis or other demyelinating diseases, or Felty’s syndrome.
• With neutropenia (absolute neutrophil count < 1500/mm3) at screening

Exclusie criteria - Cohort 1 en 2:
• Zwangere of zogende patiënten, waarbij de zwangerschap wordt gedefinieerd als de toestand van een vrouw vanaf de conceptie en tot de beëindiging van de zwangerschap, bevestigd door een positieve hCG laboratoriumtest.
• Vrouwelijke patiënten van vruchtbare leeftijd, gedefinieerd als alle vrouwen fysiologisch in staat om zwanger te worden, tenzij zij effectieve methoden van anticonceptiegebruiken tijdens de studie behandeling. Effectieve anticonceptie methoden zijn gedefinieerd in het protocol.
• Actieve of terugkerende bacteriële, fungale of virale infectie op het moment van screening, waaronder patiënten met tekenen van Human Immunodeficiency Virus (HIV), hepatitis B en hepatitis C infectie.
• Voorgeschiedenis of tekenen van tuberculose (tbc) (actieve of latente) infectie of 1 van de risicofactoren voor tuberculose (tbc) zoals gedefinieerd in het protocol.
• Onderliggende metabole, renale, hepatische, infectieuze of gastro-intestinale aandoeningen die naar het oordeel van de onderzoeker immunosuppressief werken en voor de patiënt een onaanvaardbaar risico met zich meebrengen bij deelname aan een munomodulerende therapie. In het bijzonder, klinisch bewijs of voorgeschiedenis van multiple sclerose of andere demyeliniserende ziekten, of het syndroom van Felty.
• Neutropenie (absoluut aantal neutrofielen <1500/mm3) op moment van screening

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients in clinical remission on canakinumab 4 mg/kg (+/- concomitant NSAID only) who are able to remain at a reduced canakinumab dose (2mg/kg every 4 weeks) or prolonged canakinumab dose interval (4mg/kg every 8 weeks) for at least 24 consecutive weeks

Aantal met canakinumab 4 mg/kg behandelde patiënten in klinsiche remissie (+/- NSAID alleen als co-medicatie) dat in staat is op een lagere dosis canakinumab (2 mg/kg om de 4 weken) of bij een verlengd canakinumab dosisinterval (4 mg/kg elke 8 weken) gedurende ten minste 24 opeenvolgende weken in klinische remissie te blijven

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks from randomization

24 weken na randomisatie

E.5.2

Secondary end point(s)

long-term safety and tolerability of canakinumab

veiligheid en verdraagbaarheid van canakinumab op lange termijn

E.5.2.1

Timepoint(s) of evaluation of this end point

Duration of trial

Gedurende de gehele studie

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

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

• Immunogenicity
• Antibodies against vaccine antigen
• Soluble and cellular biomarkers

•Immunogeniciteit
• Antistoffen tegen vaccin
• Oplosbare en cellulaire 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)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

Argentina

Austria

Belgium

Brazil

Canada

France

Germany

Hong Kong

Hungary

Israel

Italy

Mexico

Netherlands

Peru

Poland

Russian Federation

Spain

Sweden

Turkey

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

This study is planned to run until all randomized patients fall into one of the following categories:
1. Patient completed Part II
2. Patient has met criteria for maintenance regimen failure
3. Patient has been being prematurely withdrawn / discontinued from the study
4. Patient has been lost to follow-up.

Deze studie duurt totdat alle gerandomiseerde patiënten vallen in een van de volgende categorieën:
1 Patiënt heeft deel II voltooid
2 Patiënt voldoet aan criteria lack of efficay
3 Patiënt is vroegtijdig gestopt met de studie
4 Patiënt is lost to follow-up

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

163

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

103

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients below 18 years old for which Parent’s or legal guardian’s written informed consent will be collected in addition to the child’s assent

Voor patiënten jonger dan 18 jaar wordt schriftelijk toestemming gevraagd van ouder of voogd in aanvulling op de instemming van het kind (indien mogelijk)

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

F.4.2.2

In the whole clinical trial

180

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)

Patients who are discontinued from the study prematurely will be expected to complete an EOS visit and will treated as per local standard medical practice. If a patient who fully completes the study and whose disease relapses within 12 months from discontinuation of canakinumab, the patient will be allowed to receive canakinumab at 4 mg/kg/q4weeks or until the drug is marketed for SJIA in the participating country.

Patiënten die vroegtijdig stoppen met de studie worden gevraagd terug te komen voor een EOS (End of Study) visite en zullen worden behandeld volgens de lokale behandel richtlijnen. Patiënten die deze studie volledig hebben doorlopen en een terugval krijgen binnen 12 maanden na laatste canakinumab dosis mogen worden behandeld met canakinumab 4mg/kg om de 4 weken totdat het regulier is te verkrijgen.

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

2014-09-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-12-23

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

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