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
- Conditions
- inflammation of the jointsrheumatism10003816
- Registration Number
- NL-OMON35648
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
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 (Petty, et al 2004) 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) (Not
required for CACZ885G2305 roll-over patients)
* Documented spiking, intermittent fever (body temperature > 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 < 10 mg/L) (Patients rolling-over
from the CACZ885A2203 or CACZ885G2305 study will not be
required to have a CRP > 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 (< 5 mm induration) or negative
QuantiFERON 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). If the patient has a history of Bacillus Calmette-
Guérin (BCG) vaccination, then a QuantiFERON test should be performed in place of a
PPD test. (Not required for CACZ885G2305 roll-over patients)
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.
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy variable for Part I is the proportion of patients who were<br /><br>on steroids at entry into Part I and who were able to taper steroid as per<br /><br>protocol.<br /><br>The primary efficacy variable is the time to flare in Part II.</p><br>
- Secondary Outcome Measures
Name Time Method