Behçet`s Disease MedDRA version: 14.0 Level: PT Classification code 10004213 Term: Behcet's syndrome System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: Ilaris
Product Name: Ilaris
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2
Sponsors
University Hospital of Tübingen
Eligibility
Sex/Gender
All
Inclusion 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
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 50%) and Uveitis Scoring system (defined as posterior uveitis score improving by > 50%) is to be evaluated.;Timepoint(s) of evaluation of this end point: At week 24 (close-out) | — |
Secondary
| Measure | Time frame |
|---|---|
| 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) | — |
Countries
Germany
Outcome results
None listed