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
- Conditions
- Active systemic manifestations of Systemic Juvenile Idiopathic Arthritis (SJIA)MedDRA version: 9.1Level: LLTClassification code 10059176Term: Juvenile idiopathic arthritis
- Registration Number
- EUCTR2008-005479-82-HU
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 214
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) (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 Novartis Confidential Page 13 WP Clean Version No. 2.0 (incorp Amend 1) Protocol No. CACZ885G2301 (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 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 test 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.
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
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
•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-activaton 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 within 4 weeks prior to Baseline visit
•Adalimumab within 8 weeks prior to the Baseline visit
•Infliximab within 12 weeks prior to the Baseline visit
•Rituximab within 26 weeks prior to the B
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method