inflammation of the joints rheumatism
Conditions
Interventions
Investigational and reference therapy:
Patients will be dosed every 4 weeks:
* Part I: a single dose of canakinumab (4 mg/kg)
* Part II: canakinumab (4 mg/kg) or placebo in a 1:1 ratio
The maximal to
Sponsors
Novartis
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
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 38°C) for at least 1 day during the screening period within 1 week before first canakinumab/placebo dose (Patients rolling-over from the CACZ885A2203 or CACZ885G2305 study will not be required to have fever for study entry) * C-reactive protein (CRP) > 30 mg/L (normal range 30 mg/L) 5. Patient*s willingness to discontinue anakinra, rilonacept, tocilizumab or other experimental drug under close monitoring (Please refer to Section 5.2 - Exclusion criteria #12 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 per day of oral prednisone (or equivalent) for at least 3 days prior to baseline (Day 1) 7. Negative Purified Protein Derivative (PPD) test (
Exclusion criteria
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 (e.g. Tanner stage 2 or above), 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 and/or * 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. Diagnosis of active macrophage-activation syndrome (MAS) (Ravelli, Magni-Manzoni and Pistorio 2005) within 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. 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) 11. Presence of moderate to severe impaired renal function as indicated by clinically significantly abnormal creatinine (* 1.5 x upper normal limit (ULN)) or urea values or abnormal urinary constituents (e.g., albuminuria) at screening. Evidence of urinary obstruction or difficulty in voiding at screening. 12. Use of the following therapies: * Anakinra within 24 hours prior to Baseline visit * Rilonacept within 1 week prior to Baseline visit * Tocilizumab within 3 weeks prior to Baseline visit * Etanercept
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy variable for Part I is the proportion of patients who were on steroids at entry into Part I and who were able to taper steroid as per protocol. The primary efficacy variable is the time to flare in Part II. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Maintenance of adapted ACR Pediatric 30/ 50/ 70/ 90/ 100 criteria during Part II 2. Change in disability over time by CHAQ© 3. Change in HRQoL over time by CHQ-PF50© 4. Proportion of patients who reached a steroid dose * 0.2 mg/kg at end of Part Ic 5. Steroid level at end of Part Ic and change from baseline to end of Part Ic 6. Proportion of patients achieving the adapted ACR Pediatric 30/50/70/90/100 criteria in Part I 7. proportion of patients who have body temperature *38°C at Day 3 in Part I 8. Time to adapted ACR Pediatric 50 criteria and normal CRP ( | — |
Countries
Netherlands
Outcome results
None listed