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

Arthritis, Juvenile Rheumatoid Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00426218
• Other study ID #: CACZ885A2203
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 23, 2007
• Last updated: August 8, 2011
• Start date: December 2006

Study information

• Verified date: August 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 20 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Arthritis, Juvenile Rheumatoid

Intervention

Drug:
• ACZ885

Locations

Country	Name	City	State
Italy	Novartis Investigative site	Origgio

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety, tolerability and immunogenicity of subcutaneous (s.c.) ACZ885
Primary	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.
Primary	pharmacokinetics of ACZ885
Primary	To assess pharmacokinetics (PK) / pharmacodynamics (PD) relationships in order to derive a dose and dosing regimen
Secondary	proportion of patients with inactive disease at each dose level.
Secondary	To investigate the possibility of corticosteroid tapering.
Secondary	biomarker and pharmacogenomic characterization of patients at baseline and to evaluate the treatment response to ACZ885.