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

Primary Purpose

Arthritis, Juvenile Rheumatoid

Status
Completed
Phase
Phase 1
Locations
Italy
Study Type
Interventional
Intervention
ACZ885
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Arthritis, Juvenile Rheumatoid focused on measuring Systemic Juvenile Idiopathic Arthritis, Immunogenicity, Pharmacokinetics, Anti-IL-1ß Monoclonal Antibody, ACZ885, SJIA, Pediatrics

Eligibility Criteria

4 Years - 20 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

ACZ885

Outcomes

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.

Full Information

First Posted
January 23, 2007
Last Updated
August 8, 2011
Sponsor
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00426218
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Novartis

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Juvenile Rheumatoid
Keywords
Systemic Juvenile Idiopathic Arthritis, Immunogenicity, Pharmacokinetics, Anti-IL-1ß Monoclonal Antibody, ACZ885, SJIA, Pediatrics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
26 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
ACZ885
Intervention Type
Drug
Intervention Name(s)
ACZ885
Primary Outcome Measure Information:
Title
Safety, tolerability and immunogenicity of subcutaneous (s.c.) ACZ885
Title
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.
Title
pharmacokinetics of ACZ885
Title
To assess pharmacokinetics (PK) / pharmacodynamics (PD) relationships in order to derive a dose and dosing regimen
Secondary Outcome Measure Information:
Title
proportion of patients with inactive disease at each dose level.
Title
To investigate the possibility of corticosteroid tapering.
Title
biomarker and pharmacogenomic characterization of patients at baseline and to evaluate the treatment response to ACZ885.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis
Organizational Affiliation
Investigative site
Official's Role
Principal Investigator
Facility Information:
Facility Name
Novartis Investigative site
City
Origgio
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
30269054
Citation
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.
Results Reference
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Safety, Efficacy and Pharmacokinetics of Subcutaneous ACZ885 in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA)

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