Clinical Trials Register

Summary
EudraCT Number:	2012-003054-92
Sponsor's Protocol Code Number:	CACZ885G2402
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-12-18
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

Czechia - SUKL

A.2

EudraCT number

2012-003054-92

A.3

Full title of the trial

An open-label, multi-arm, non-comparative safety and tolerability study of canakinumab (ACZ885) in patients with active Systemic Juvenile Idiopathic Arthritis (SJIA)

Otevřené, mnohoramenné, nekomparativní klinické hodnocení bezpečnosti a snášenlivosti kanakinumabu (ACZ885) u pacientů s aktivní systémovou juvenilní idiopatickou artritidou (SJIA)

A.3.1

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

A study to check how safe, beneficial and tolerable the drug canakinumab is for patients with systemic juvenile idiopathic arthritis (SJIA)

Studie určená k ověření bezpečnosti, prospěšnosti a snášenlivosti kanakinumabu u pacientů se systémovou juvenilní idiopatickou artritidou (SJIA)

A.3.2

Name or abbreviated title of the trial where available

β-SPECIFIC 4 Patients

A.4.1

Sponsor's protocol code number

CACZ885G2402

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 s.r.o.
B.5.2	Functional name of contact point	Informační služba - klin. hodnocení
B.5.3	Address:
B.5.3.1	Street Address	Na Pankráci 1724/129
B.5.3.2	Town/ city	Praha 4
B.5.3.3	Post code	140 00
B.5.3.4	Country	Czech Republic
B.5.4	Telephone number	+420225 775 207
B.5.5	Fax number	+420 225 775 205
B.5.6	E-mail	dotazy.klinickehodnoceni@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	ILARIS
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Powder for 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 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.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	Lyophilisate for 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

Active systemic manifestations of Systemic Juvenile Idiopathic Arthritis (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. Symptoms include fever, rash, anemia and joint pain.

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10059176
E.1.2	Term	Juvenile idiopathic arthritis
E.1.2	System Organ Class	100000004859

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

Part I: To evaluate the long-term safety and tolerability of canakinumab and to assess the retention rate of canakinumab treated patients

Part II: To assess the long-term safety and tolerability of canakinumab

E.2.2

Secondary objectives of the trial

Part I: - To assess efficacy as a percentage of patients who meet the adapted pediatric ACR, its individual components, and the Juvenile Arthritis Disease Activity Score [JADAS] over time
- To assess efficacy in the percentage of patients who reported failure to anakinra and tocilizumab using the adapted pediatric ACR
- To evaluate the level of systemic corticosteroid tapering achieved
- To assess change in disability over time by use of the cross culturally adapted and validated version of the CHAQ©
Part II: - To assess time to treatment failure
- To assess efficacy as a percentage of patients who meet the adapted pediatric ACR, its individual components, and the Juvenile Arthritis Disease Activity Score [JADAS] over time
- To evaluate the level of canakinumab tapering achieved after randomization to the dose reduction or dose interval prolongation treatment arm
- To assess change in disability over time by use of the cross culturally adapted and validated version of the CHAQ©

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Cohort 1:
1. All patients currently enrolled in study CACZ885G2301E1, including patients who discontinued canakinumab therapy for inactive disease in CACZ885G2301E1 as per physician discretion and who are now currently in a flare and require canakinumab therapy again

Cohort 2:
1. Male and female patients aged ≥ 2 to < 20 years at the time of the screening visit
2. 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:
o Evanescent non-fixed erythematous rash,
o Generalized lymph node enlargement,
o Hepatomegaly and/ or splenomegaly,
o Serositis
3. Active systemic disease 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
4. Patient’s willingness to discontinue anakinra, rilonacept, tocilizumab or other experimental drug under close monitoring
5. Patients who are scheduled to receive an immunization, according to their local vaccination guidelines, with an inactivated vaccine and willing to participate in the assessment schedule for vaccinated patients

Other protocol-defined inclusion criteria may apply.

E.4

Principal exclusion criteria

Cohort 1 and Cohort 2:
1. Active or recurrent bacterial, fungal or viral infection at the time of enrollment
2. 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
3. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
4. Live vaccinations within 3 months prior to the start of the study

Cohort 2:
The following additional key exclusion criteria apply for Cohort 2.
1. Presence of moderate to severe impaired renal function
2. Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests at screening
3. History/evidence of macrophage activation syndrome within the previous 6 months

Other protocol-defined exclusion criteria may apply.

E.5 End points

E.5.1

Primary end point(s)

Long-term safety and tolerability of canakinumab and the retention rate of canakinumab-treated patients will be evaluated by monitoring of serious adverse events and adverse events leading to discontinuation of study drug

E.5.1.1

Timepoint(s) of evaluation of this end point

Days 1 to 533

E.5.2

Secondary end point(s)

1.The percentage of patients who meet the adapted pediatric ACR, its individual components, and the Juvenile Arthritis Disease Activity Score [JADAS] over time
2. The level of systemic corticosteroid tapering achieved in Part I
3. The level of canakinumab tapering achieved after randomization to the dose reduction arm or dose interval prolongation treatment arm in Part II
4. The time to treatment failure in Part II

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Days 1 to 533
2. Day 1 to start of Part II
3. From start of Part II to Day 533
4. From start of Part II to Day 533

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

Yes

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

Tolerability and immunogenicity, Cellular 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)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

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

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

Argentina

Austria

Belgium

Brazil

Canada

Czech Republic

France

Germany

Greece

Hungary

Israel

Italy

Netherlands

Peru

Poland

Russian Federation

Spain

Sweden

Switzerland

Turkey

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

LPLV

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

Yes

F.1.1

Number of subjects for this age range:

220

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:

100

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

100

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

paediatric patients

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

170

F.4.2.2

In the whole clinical trial

220

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)

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

2013-03-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-04-18

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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