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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00426218
First received: January 23, 2007
Last updated: August 8, 2011
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Arthritis, Juvenile Rheumatoid
Drug: ACZ885
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety, Efficacy and Pharmacokinetics of Subcutaneous ACZ885 in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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

Secondary Outcome Measures:
  • 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.

Estimated Enrollment: 26
Study Start Date: December 2006
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
ACZ885
Drug: ACZ885

  Eligibility

Ages Eligible for Study:   4 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00426218

Locations
Italy
Novartis Investigative site
Origgio, Italy
Sponsors and Collaborators
Novartis
Investigators
Principal Investigator: Novartis Investigative site
  More Information

No publications provided

Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00426218     History of Changes
Other Study ID Numbers: CACZ885A2203
Study First Received: January 23, 2007
Last Updated: August 8, 2011
Health Authority: Italy: Ministry of Health

Keywords provided by Novartis:
Systemic Juvenile Idiopathic Arthritis
Immunogenicity
Pharmacokinetics
Anti-IL-1ß Monoclonal Antibody
ACZ885
SJIA
Pediatrics

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014