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)

• Register: EUCTR
• Last refreshed on: 19 December 2023
• Main ID: EUCTR2010-024152-29-DE
• Date of registration: 21/06/2011
• Prospective Registration: Yes
• Primary sponsor: University Hospital of Tübingen
• Public title: 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)
• Scientific title: Canakinumab for Behçet`s Disease Resistant to Standard Treatment (CanBeDisT) - CanBeDisT
• Date of first enrolment: 02/09/2011
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024152-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Contacts

• Affiliation: STZ eyetrial

• Affiliation: STZ eyetrial

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
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) yes
F.1.3.1 Number of subjects for this age range

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 m

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Behçet`s Disease
MedDRA version: 14.0 Level: PT Classification code 10004213 Term: Behcet's syndrome System Organ Class: 10021428 - Immune system disorders

Intervention(s)

Trade Name: Ilaris
Product Name: Ilaris
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: At week 24 (close-out)

Main Objective: 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)).

Secondary Objective: 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

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.

Secondary Outcome(s)

Secondary end point(s): 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

Timepoint(s) of evaluation of this end point: At week 24 (close-out)

Secondary ID(s)

Ilaris

Canakinumab

Source(s) of Monetary Support

Novartis Pharma GmbH

Ethics review

Status: Approved
Approval date: 30/08/2011
Contact: