Clinical Trials Register

Summary
EudraCT Number:	2010-024152-29
Sponsor's Protocol Code Number:
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-06-21
Trial 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

2010-024152-29

A.3

Full title of the trial

Canakinumab for Behçet`s Disease Resistant to Standard Treatment
(CanBeDisT)

A.3.1

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

An open-label study to evaluate efficacy and tolerability of Canakinumab in patients with Behçet Disease who do not respond to standard treatment (Eine offene Studie zur Wirksamkeit und Verträglichkeit von Canakinumab bei Patienten mit Morbus Behçet, die auf die übliche Behandlung nicht ansprechen)

A.3.2

Name or abbreviated title of the trial where available

CanBeDisT

A.4.1

Sponsor's protocol code number

A.5.4

Other Identifiers

Name:	Active ingredient	Number:	Canakinumab
Name:	Brand name	Number:	Ilaris

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	University Hospital of Tübingen
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	STZ eyetrial
B.5.2	Functional name of contact point
B.5.3	Address:
B.5.3.1	Street Address	Schleichstr. 12-16
B.5.3.2	Town/ city	Tübingen
B.5.3.3	Post code	72076
B.5.3.4	Country	Germany
B.5.4	Telephone number	49 7071298 4898
B.5.5	Fax number	49707129 50 21
B.5.6	E-mail	barbara.wilhelm@stz-eyetrial.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 Pharma GmbH
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	Ilaris
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.3.9.4	EV Substance Code	SUB30137
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	No
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

Behçet`s Disease

E.1.1.1

Medical condition in easily understood language

Behçet`s Disease is an inflammatory disease involving mainly blood vessels. Its main symptoms are oral and genital ulcerations, skin lesions and CNS manifestations.

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10004213
E.1.2	Term	Behcet's syndrome
E.1.2	System Organ Class	10021428 - Immune system 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

The objective of this clinical pilot study is to evaluate the efficacy, safety and tolerability of canakinumab in treatment resistant Behçet`s disease.
The primary endpoint is to evaluate the percentage of patients achieving Major Response according to BDCAFadapted (Behçet`s Disease Current Activity Form (adapted from observation period of 4 weeks in the past to one week in the past)), defined as improvement by >50%) and Uveitis Scoring system (defined as posterior uveitis score improving by > 50%)- the latter to be used in case of uveitis only. The primary endpoint will be determined at week 24 (close out)).

E.2.2

Secondary objectives of the trial

Percentage of patients achieving remission according to BDCAFadapted (becoming <1)
• Percentage of patients achieving remission according to Uveitis Scoring System (score becoming < 1)
• Reduction in Birmingham Vasculitis Score (BVAS)
• Reduction in visual analog scale for disease activity (patient/physician)
• Reduction in number and size of oral and cutaneous lesions
• Reduction of DAS44 (in case of arthritis)
• Improvement of visual acuity (in case of ocular disease)
• Quality of life as recorded by HAQ and FfbH, EuroQuol
• Dose reduction of concomitant glucocorticosteroids (GC)
• Time to remission/major response
• Duration of remission/major response – time to relapse
• Improvement of laboratory activity markers (ESR, CRP, IL-18, SAA, S100 A12 and A9)
• reduction of gamma delta T cells

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients with BD fulfilling the international study group criteria (ISBD) from 1990 with active disease defined as BDCAF >3 and/or posterior uveitis score >2
• Treatment resistant to standard treatment according to EULAR guidelines (colchicine, azathioprine, methotrexate (plus glucocorticosteroids), in case of ocular disease also TNF-antagonists or interferon-alpha.
• Age ≥ 18 years ≤ 65 years
• Capable of understanding the purposes and risks of the study, able to give informed consent and to comply with the study requirements
• Women of childbearing age must have a negative urine pregnancy test (UPT) within 48 hours prior to starting study drug and at the end of the trial and must not be lactating.
• Female subjects of non-childbearing potential must meet at least one of the
following criteria:
Postmenopausal females, defined as:
Females over the age of 60 years.
Females who are 45 to 60 years of age must be amenorrhoic for at least 2 years.
Females who had a hysterectomy and/or bilateral oophorectomy.
Protocol: CanBeDisT Version 1.0 29.04.2011
18
• Subjects of both genders with reproductive potential who are sexually active
agree to use contraception throughout the course of the study and for at least
3 months after completion of their study participation.
• Women of childbearing potential have to use a highly effective method of birth control defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, hormonal IUDs combined with barrier methods (e.g. condom, diaphragm or spermicide), sexual abstinence or vasectomised partner.
• Negative PPD or Quantiferon test and uneventful chest X ray from last 12
months (negative for tuberculosis)
• Negative serology for HIV, hepatitis ABC
• Prior Medication:
Patients with non-ocular, non-severe disease (mucocutaneuous, arthritis,
thrombophlebitis) must have had colchicine and/or azathioprine without
sufficient efficacy before entering the study.
Patients with ocular BD must have been treated at least with azathioprine,
and/or cyclosporin A plus glucocorticosteroids without effect before entering
the study. Interferon-alpha and TNF antagonists may have also been
ineffective before entering the study.

E.4

Principal exclusion criteria

Patients under 18 years
• Severe, life threatening BD manifestations (pulmonary arterial aneurysms,
CNS)
• Female patients not willing to use contraceptives
• Signs of tuberculosis in chest x-ray during the past 12 months before study
entry
• Hemoglobin < 8 g/dl, WBC < 3000/ul, platelet count < 100.000/ul, GFR/MDRD
< 50 ml/min/1,73m2, AST/ALT > 2x upper normal limit, alkaline phosphatase >
2x upper normal limit
• Known HIV antibody, hepatitis B surface antigen, and/or hepatitis C antibody
History of malignancy within 5 years prior to study entry other than carcinoma
in situ of the cervix, or adequately treated, non-metastatic squamous or basal
cell carcinoma of the skin
• History of severe allergic reaction to humanized or murine monoclonal
antibodies
• Fever or infection requiring antibiotic treatment within 3 weeks prior to
screening, history of recurrent infection or predisposition to infections
• Immunodeficiency
• Demyelinating disease
• Known presence or suspicion of active or recurrent bacterial, fungal or viral
infection at the time of enrollment, where an IL-1 blocker might have an impact
on underlying severe immunocompromising diseases as e.g. evidence of
Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C
infections (based on history and/or clinical findings).
• One of the risk factors for TB such as but not limited or exclusive to:
a. History of any of the following: residence in a congregate setting (e.g.
jail or prison, homeless shelter, or chronic care facility), substance
abuse (e.g. injection or noninjection); health-care workers with
unprotected exposure to patients who are at high risk of TB or patients
with TB disease before the identification and correct airborne
precautions of the patient, or
b. Close contact (i.e. share the same air space in a household or other
enclosed environment for a prolonged period (days or weeks, not
minutes or hours)) with a person with active pulmonary TB disease
within the last 12 months.
History of ongoing, chronic or recurrent infectious disease or evidence of
tuberculosis infection determined as defined by local guidelines/ local medical
practice. If presence of tuberculosis is established then treatment (according
to local guidelines) must have been completed prior to randomization.
• Significant medical problems, including but not limited to the following:
uncontrolled hypertension (= 200/105 mmHg), congestive heart failure [New
York Heart Association Stage D], uncontrolled diabetes type I and II (recent
blood glucose > 300 mg/dl), thyroid disease (unless the patient is taking a
stable dose of thyroid hormone or anti-thyroid medications (hyperthyroidism)
for at least 12 weeks), which in the opinion of the Investigator will exclude the
patient from the study (can be discussed on a case by case basis with
Novartis).
• Life vaccine within 3 months prior to screening. Live seasonal flu /H1N1
vaccines are permitted > 2 weeks prior to screening
Major surgery within 4 weeks prior to week 1 (injection of canakinumab)
• Participation in an investigational drug trial within 4 weeks prior to screening
• Presence of absolute contraindications for canakinumab as mentioned in the
product information (Appendix 1)
• Presence of relative contraindications for canakinumab as mentioned in the
product information (Appendix) if the disorder leading to the relative
contraindication can not sufficiently managed by concomitant medication.
• Subjects with medically significant co-morbid conditions that impair normal
activities, require systemic corticosteroids or immunosuppressives, or any
medical condition that would likely have an impact on the participant´s ability
to comply with the study visit schedule
• Any current or history of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication

E.5 End points

E.5.1

Primary end point(s)

The efficacy of the investigational drug will be assessed by established scoring systems for Behçet`s disease (Behçet`s disease current activity form, BDCAF) and the Uveitis scoring system (in case of ocular manifestation).
The percentage of patients achieving Major Response according to BDCAFadapted (Behçet`s Disease Current Activity Form (adapted from observation period of 4 weeks in the past to one week in the past), defined as either improvement by >50%) and Uveitis Scoring system (defined as posterior uveitis score improving by > 50%) is to be evaluated.

E.5.1.1

Timepoint(s) of evaluation of this end point

At week 24 (close-out)

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

At week 24 (close-out)

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

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

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

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

Premature termination of this clinical study may occur because of a regulatory authority decision, drug safety as well as at the discretion of the Sponsor or Novartis Pharma GmbH.

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.1.3

Elderly (>=65 years)

Yes

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

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

F.4.2.2

In the whole clinical trial

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)

Treatment of subjects after the end of the study will be at the discretion of the investigator.

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

2011-09-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-08-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-07-14

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IMP with orphan designation in the indication
Orphan Designation Number:
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