Clinical Trials Register

Summary
EudraCT Number:	2011-001027-20
Sponsor's Protocol Code Number:	CACZ885GDE01T
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-12-05
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

Germany - PEI

A.2

EudraCT number

2011-001027-20

A.3

Full title of the trial

A Multi-Centre, Placebo-Controlled Phase II Study of Canakinumab for the Treatment of Adult-onset Still's disease (AOSD) including an open-label long term extension.

Eine multizentrische, Plazebo-kontrollierte Phase II-Studie mit Canakinumab zur Behandlung des Still-Syndroms des Erwachsenen inklusive einer Verlängerungsphase ohne Plazebokontrolle.

A.3.1

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

A Multi-Centre, Placebo-Controlled Phase II Study of Canakinumab for the Treatment of Adult-onset Still's disease (AOSD) including an open-label long term extension.

Eine multizentrische, Plazebo-kontrollierte Phase II-Studie mit Canakinumab zur Behandlung des Still-Syndroms des Erwachsenen inklusive einer Verlängerungsphase ohne Plazebokontrolle.

A.3.2

Name or abbreviated title of the trial where available

CONSIDER

A.4.1

Sponsor's protocol code number

CACZ885GDE01T

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	Charité - Universitätsmedizin Berlin
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Charité - Universitätsmedizin Berlin
B.5.2	Functional name of contact point	Jan Zernicke
B.5.3	Address:
B.5.3.1	Street Address	Chariteplatz 1
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	10117
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4930450513227
B.5.5	Fax number	+4930450513986
B.5.6	E-mail	jan.zernicke@charite.de

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 Limited
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	EU/1/09/564/004
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 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	Comparator
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 Limited
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	EU/1/09/564/004
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 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	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

adult onset Still's disease (AOSD)

Still Syndrom des Erwachsenen

E.1.1.1

Medical condition in easily understood language

adult onset Still's disease (AOSD)

Still Syndrom des Erwachsenen

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10042061
E.1.2	Term	Still's disease
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 assess efficacy of Canakinumab treatment for patients with adult onset Still's disease (AOSD) and active joint involvement according to proportion of patients with significant reduction of disease activity (DAS 28 [>1,2]) after 12 week treatment period

Evaluation of the long-term safety of canakinumab in patients with AOSD and articular involvement

E.2.2

Secondary objectives of the trial

evaluation of safety of Canakinumab for patients with adult onset Still's
disease (AOSD)

evaluation of efficacy of Canakinumab for patients with AOSD and joint involvement according ACR response criteria at week 12 and week 24

proportion of patients who achieve a low disease activity (DAS28 < 3,2) or remission (DAS28 < 2,6)

documentation of change in joint mobility

to assess change in general health status using HAQ-DI and SF36-questionaire

improvement of dermal Manifestation

reduction of inflamatory lab values
(CRP, ESR, Ferritin)

Biomarker Analysis

Description of the long-term efficacy of canakinumab in patients with AOSD according to EULAR response criteria (proportion of patients showing prolonged clinically improvement according to DAS28 low-disease activity [< 3.2] and remission [< 2.6], reduction of flares and glucocorticoid intake).

Evaluation if a reduced dosage of canakinumab can be used to control disease activity

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

° sub-study is integrated in main study
protocol but with a seperate patient
information and patient consent form
° title: substudy to analyse Biomarkers
like inflammatory proteins and gene
° main objectives:
- soluble proteins to assess patho-
mechanism like IL-6 and IL-18,
S100 as inflammtory marker
- pharmacogenomic analysis
- mRNA expression to assess
relationship to macrophage
activating syndrome
- pharmacogenetic analyses to identify
Single Nucleotide Polymorphism (SNP)

E.3

Principal inclusion criteria

written informed consent

men and women ≥ 18 years and ≤ 75 years

diagnosis of adult onset Still's disease according Yamaguchi et al. criteria (J Rheumatology 1992)

disease activity (DAS28 >3,2) at Screening

joint involvement defined as minimum 4 painfull and 4 swollen joints at Screening and Baseline (28 joint count)

if treated with NSAID's: stable treatment for a minimum of 2 weeks prior to randomisation

if treated with corticosteroids: stable treatment for a minimum of 1 week prior to randomisation (≤ 10 mg/ day)

if on conventional DMARD therapy: stable treatment for a minimum of 6 weeks prior to randomisation

washout of biologic DMARD's

effective method for contraception

E.4

Principal exclusion criteria

prior treatment with two or more doses of IMP

intraarticular or intravenous injection with corticosteroids 4 weeks before randomisation

treatment with narcotic analgetics (excluding permitted concomitant medications such as Tramadol and Codein)

diagnosis of other, severe, chronic-inflammatory diseases

positive hepatitis B Antigen (HBsAg), hepatitis C antibody and/ or HIV-antibody

relevant active infection

positive screening for latent tuberculosis (if patient is taking adequate/isoniazid prophylaxis for 4 weeks before first IP administration, this patient may be randomized.)

elevated lab results: AST, ALT Bilirubin, Creatinine

non adequate hematologic lab result

history of neoplasm (with exception of curative treated non-melanoma neoplasm of the skin and carcinoma in situ of cervix)

relevant cardial or pulmonary diseases

macrophage activating syndrome (MAS)

vaccination with life vaccine

a history of alcohol or drug abuse within last 12 months

blood donation or blood loss ≥ 400 ml within last 8 weeks

pregnancy or breastfeeding

E.5 End points

E.5.1

Primary end point(s)

Disease activity score 28 Joints (DAS28)

E.5.1.1

Timepoint(s) of evaluation of this end point

at Screening, Baseline and at week 12

E.5.2

Secondary end point(s)

Joint manifestation:
1.DAS28 (Disease activity score)
2.ACR (American College of Rheumatology) Response Criteria and EULAR response criteria for low disease activity (DAS28 < 3.2) and remission (DAS28 < 2,6)

Assessment of the level of disability and of quality of life:
1.Health Assessment Questionnaire Disability Index (HAQ-DI)
2.SF-36 health Survey

Laboratory tests
1.Serological markers for inflammatory reactions (CRP, ESR, ferritin)
2.Immunogenity (anti-canakinumab antibodies) will be established at all visits, in the case of episodes of illness and with MAS. In the event of an anaphylactic reaction occurring, samples will be investigated following the injection and at intervals of 8 weeks.

E.5.2.1

Timepoint(s) of evaluation of this end point

core-study: week 0, 4, 8, 12, 16, 20 and week 24

in long term extension phase (LTE): every 3 months (quarterly) up to visit month 30

safety evaluation (= secondary objective of core study and primary objective of LTE-phase): every month up to month 33

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

rescue therapy with open treatment in non-responders at week 12 and a 2 y. extension phase

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

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

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

normally: LVLS

exceptions: patients withdrawing consent, adverse events wich do not allow continuation of this trial

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

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:

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

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.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)

after early discontinuation or week 24 visit (EOS) patients will get two options: referral to a rheumatologist (outpatient care) or to remain in the hands of treating physician (rheumatologist) during the trial

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

2012-04-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2018-05-04

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