Safety, Efficacy and Pharmacokinetics of Subcutaneous ACZ885 in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA)

• ClinicalTrials.gov Identifier: NCT00426218
• Recruitment Status: Completed
• First Posted: January 24, 2007
• Last Update Posted: August 9, 2011
• Sponsor: Novartis
• Information provided by: Novartis

Tracking Information

• First Submitted Date: January 23, 2007
• First Posted Date: January 24, 2007
• Last Update Posted Date: August 9, 2011
• Study Start Date: December 2006
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 23, 2007)

• Safety, tolerability and immunogenicity of subcutaneous (s.c.) ACZ885
• To assess the initial efficacy profile of s.c. ACZ885: % responder to treatment and time to relapse and control the systemic manifestations of SJIA such as fever.
• pharmacokinetics of ACZ885
• To assess pharmacokinetics (PK) / pharmacodynamics (PD) relationships in order to derive a dose and dosing regimen

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 23, 2007)

• proportion of patients with inactive disease at each dose level.
• To investigate the possibility of corticosteroid tapering.
• biomarker and pharmacogenomic characterization of patients at baseline and to evaluate the treatment response to ACZ885.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Efficacy and Pharmacokinetics of Subcutaneous ACZ885 in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA)
• Official Title: Safety, Efficacy and Pharmacokinetics of Subcutaneous ACZ885 in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA)
• Brief Summary: This study is a multi-center, open label, repeated dose, range finding study to evaluate the safety, tolerability, immunogenicity, pharmacokinetics and efficacy of ACZ885, a fully human anti-interleukin-1B (anti-IL-1B) monoclonal antibody, given subcutaneously in pediatric subjects with active SJIA.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Arthritis, Juvenile Rheumatoid
• Intervention: Drug: ACZ885

Study Arms

Experimental: 1

ACZ885

Intervention: Drug: ACZ885

• Publications *: Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat NM, Horneff G, Kasapcopur O, Schneider R, Anton J, Barash J, Berner R, Corona F, Cuttica R, Fouillet-Desjonqueres M, Fischbach M, Foster HE, Foell D, Radominski SC, Ramanan AV, Trauzeddel R, Unsal E, Levy J, Vritzali E, Martini A, Lovell DJ; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials. Ann Rheum Dis. 2018 Dec;77(12):1710-1719. doi: 10.1136/annrheumdis-2018-213150. Epub 2018 Sep 29.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: January 23, 2007): 26
• Original Enrollment: Same as current
• Study Completion Date: Not Provided
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female subjects aged 4 to 20 years
• Female subjects of child-bearing potential may participate if they have a negative pregnancy test at screening and prior to dosing, and are willing to use, if adequate for age, an effective method of contraception (e.g. birth control pills, abstinence, double-barrier contraception, etc.) during the study (from the date of screening) and for at least 3 months following the last dose.
• Patient meets the diagnostic criteria for SJIA, has at least 6 months disease duration and has active disease at the time of enrollment defined as follows:

At least 2 joints with active arthritis (using ACR definition of active joint) Spiking, intermittent fever (body temperature > 38°C only for several hours during the day) CRP > 50 mg/L (normal range < 10 mg/L).

• Patients who have not taken Anakinra, who have discontinued or failed anakinra (according to physician's decision) or are willing to discontinue anakinra use under close monitoring (run in phase) until relapse (reappearance of fever and/or CRP increase).
• Willing to discontinue second line agent such as disease-modifying and immunosuppressive drugs, not including methotrexate and corticosteroids.
• Body weight of at least 12 kg.

Exclusion Criteria:

-Use of: Etanercept in the four weeks prior to the Baseline visit Adalimumab in the eight weeks prior to the Baseline visit Infliximab in the eight weeks prior to the Baseline visit Any other investigational biologics in the eight weeks prior to the Baseline visit Leflunomide in the four weeks prior to the Baseline visit. Documentation of a completion of a full cholestyramine elimination procedure after most recent leflunomide use will be required Thalidomide in the four weeks prior to the baseline visit Growth hormone in the four weeks prior to the baseline visit Cyclosporine in the four weeks prior to the Baseline visit Sulfasalazine or hydroxychloroquine in the eight weeks prior to the Baseline visit i.v. immunoglobulin (i.v. Ig) in the eight weeks prior to the Baseline visit 6-Merceptopurine, azathioprine, cyclophosphamide, or chlorambucil, in the 24 weeks prior to the Baseline visit Wash-out period may be longer according to local requirements.

• History of recurrent bacterial, fungal or viral infection.
• Evidence of currently active bacterial, fungal or viral infection.
• Administration of live attenuated vaccine in the 3 months prior to the screening visit .
• Uncontrolled severe systemic symptoms and/or biologic features of Macrophage Activation Syndrome (hemorrhages, central nervous system dysfunction, hepatomegaly, serum fibrinogen level < 2.5 g/L, cytopenia, hypertriglyceridemia, decreased platelet count, increased aspartate transaminase, hyperferritinemia) (Ravelli, et al 2005).

Other protocol-defined inclusion/exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Years to 20 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT00426218
• Other Study ID Numbers: CACZ885A2203
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: External Affairs, Novartis
• Study Sponsor: Novartis
• Collaborators: Not Provided

Investigators

• Principal Investigator: Novartis; Investigative site

• PRS Account: Novartis
• Verification Date: August 2011