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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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9 October 2012 |
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Main ID: |
EUCTR2008-005479-82-DE |
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Date of registration:
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17/04/2009 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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Scientific title:
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A randomized, double-blind, placebo controlled, withdrawal study of flare prevention of canakinumab (ACZ885) in patients with Systemic Juvenile Idiopathic Arthritis (SJIA) and active systemic manifestations - G2301 |
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Date of first enrolment:
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24/11/2009 |
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Target sample size:
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214 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005479-82 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: no
Other: yes
Other trial design description: withdrawal study
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
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Phase:
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Countries of recruitment
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Austria
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Belgium
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Denmark
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France
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Germany
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Greece
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Hungary
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Italy
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Spain
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Sweden
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United Kingdom
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Contacts
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Key inclusion & exclusion criteria
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Inclusion criteria:
1. Parent’s or legal guardian’s written informed consent and child’s assent, if appropriate, or patient’s informed consent for = 18 years of age before any study related activity is performed.
2. Male and female patients aged = 2 to < 20 years at the time of the screening visit
3. 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:
• Evanescent nonfixed erythematous rash,
• Generalized lymph node enlargement,
• Hepatomegaly and/ or splenomegaly,
• Serositis
4. Active disease at the time of enrollment defined as follows:
• At least 2 joints with active arthritis (using ACR definition of active joint)
• Documented spiking, intermittent fever (body temperature > 38°C) for at least 3 days during the screening period (minimum duration of screening 3 days) before first canakinumab/placebo dose
• C-reactive protein (CRP) > 30 mg/L (normal range < 10 mg/L)
5. Patient’s willingness to discontinue anakinra, rilonacept, toclizumab or other experimental drug under close monitoring (Please refer to Exclusion criteria #15 for washout period.)
6. No concomitant use of second line agents such as disease-modifying and/or immunosuppressive drugs will be allowed with the exception of:
• Stable dose of methotrexate (maximum of 20 mg/ m2/ week) for at least 8 weeks prior to the screening visit, and folic/folinic acid supplementation (according to standard medical practice of the center)
• Stable dose of no more than one non-steroidal anti-inflammatory drug (NSAID) for at least 2 weeks prior to the screening visit
• Stable dose of steroid treatment = 1.0 mg/kg/day (maximum 60 mg/day for children over 60 kg) in 1-2 doses of oral prednisone (or equivalent) FOR AT LEAST 3 DAYS PRIOR baseline (Day 1)
7. Negative Purified Protein Derivative (PPD) test (< 5 mm induration) at screening or within 1 month prior to the screening visit, according to the national guidelines. Patients with a positive PPD test (= 5 mm induration) at screening may be enrolled only if they have either a negative chest x-ray or a negative QuantiFERON test (QFT-TB G In-Tube).
8. PATIENTS WHO HAVE COMPLETED STUDY CACZ885A2203 AND FLARED = 6 MONTHS AFTER THEIR LAST CANAKINUMAB DOSE WILL BE CONSIDERED “TREATMENT-NAÏVE” PATIENTS AND WILL BE REQUIRED TO MEET ALL INCLUSION/EXCLUSION CRITERIA OF CACZ885G2301 PROTOCOL.
Are the trial subjects under 18? yes
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) no
F.1.3.1 Number of subjects for this age range
Exclusion criteria:
1. Pregnant or nursing (lactating) female patients, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ mL) at screening visit
2. Female patients having reached sexual maturity, i.e. being physiologically capable of becoming pregnant UNLESS they are:
• female patients whose career, lifestyle, or sexual orientation precludes intercourse with a male partner
• using an acceptable method of contraception with a failure rate (Pearl Index (PI)) < 1. Reliable contraception should be maintained throughout the study and for 2 months after study drug discontinuation.
3. History of hypersensitivity to study drug or to biologics
4. Biologic features of MAS [such as hemorrhages, central nervous system dysfunction, hepatomegaly, plasma fibrinogen level < 2.5 g/L, cytopenia, hypertriglyceridemia, decreased platelet count, increased aspartate transaminase, hyperferritinemia (Ravelli, Magni-Manzoni and Pistorio 2005)] at screening or a history of recurrent pericarditis, myocarditis, serositis and/ or biologic features of MAS over the last 6 months
5. With active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infection
6. Any of the risk factors for tuberculosis (TB) such as:
• 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
• 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 year
7. With 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. In particular, clinical evidence or history of multiple sclerosis or other demyelinating diseases, or Felty’s syndrome.
8. With significant medical conditions, 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)
9. 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
10. History of autonomic dysfunction (e.g. history of fainting, orthostatic hypotension, sinus arrhythmia)
11. Uncontrolled hypertension
12. Long QT syndrome or QTc (calculated using Bazett’s formula) > 450 msec for males and > 470 msec for females at screening or baseline
13. Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests at screening such as AST, ALT, GGT, alkaline phosphatase, or serum bilirubin (must not exceed twice the upper limit value of the normal range for age)
14. Presence of moderate to severe impaired renal function as indicated by clinically significantly abnormal creatinine (= 1.5 x upper normal limit (ULN)) or urea value
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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Active systemic manifestations of Systemic Juvenile Idiopathic Arthritis (SJIA)
MedDRA version: 9.1
Level: LLT
Classification code 10059176
Term: Juvenile idiopathic arthritis
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Intervention(s)
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Product Name: Canakinumab
Product Code: ACZ885
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Canakinumab
Current Sponsor code: ACZ885
Other descriptive name: Recombinant human monoclonal antibody to human IL-1Beta of the IgG1/K class
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Subcutaneous use
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Primary Outcome(s)
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Primary end point(s): Part II: Time to flare in Part II
Part I: the proportion of patients who were on steroids at entry into Part I and who were able to taper steroid as per protocol
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Main Objective: Part II: to demonstrate that the time to flare in Part II is higher with canakinumab than with placebo.
Part I: to assess if canakinumab allows tapering of steroids as per protocol in at least 25% of the patients.
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Secondary Objective: Part II:
• To evaluate the maintenance of efficacy (length of time that patients continuously maintain or improve their adapted ACR Pediatric 30/ 50/ 70/ 90/ 100 criteria reached at entry into Part II) of canakinumab as compared to placebo
Part I:
• To evaluate number of patients who have reached a steroid dose = 0.2 mg/kg at end of Part Ic
• To evaluate the level of steroid tapering achieved at the end of Part Ic
• To evaluate the efficacy (percentage of patients who meet the adapted ACR Pediatric 30/ 50/ 70/ 90/ 100 criteria) of canakinumab in Part I
• To evaluate the efficacy of canakinumab to show clinical signs of response (percentage of patients who have body temperature = 38°C) at Day 3 in Part Ia
• To evaluate time to adapted ACR Pediatric 50 criteria and no fever and normal C-Reactive Protein (CRP <10 mg/L) during Part I
• To evaluate time to adapted ACR Pediatric 70 criteria and no fever and normal CRP (<10 mg/L) during Part I
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Secondary ID(s)
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2008-005479-82-ES
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CACZ885G2301
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Source(s) of Monetary Support
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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