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Single Patient Use of Tocilizumab in Systemic Onset Juvenile Idiopathic Arthritis

This study has been terminated.
(Hyperintensities of unclear etiology on brain MRI. Follow up revealed no progression.)
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT00868751
First received: March 24, 2009
Last updated: December 6, 2012
Last verified: December 2012
History of Changes
  Purpose

The purpose of this study is to see if tocilizumab is safe and effective for treating systemic onset Juvenile Idiopathic Arthritis (soJIA). Another purpose is to see if tocilizumab helps reduce the amount of steroids (prednisone) needed to control symptoms of soJIA.


Condition Intervention
Arthritis, Juvenile Rheumatoid
Still's Disease, Juvenile Onset
 Biological: tocilizumab

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Single Patient Use of Tocilizumab for Treatment of Steroid Dependent, Active Systemic Onset Juvenile Idiopathic Arthritis

Resource links provided by NLM:

Drug Information available for: Tocilizumab
U.S. FDA Resources

Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:
  • Efficacy of tocilizumab as defined by presence of an equal to or greater than 30% improvement in JIA core set (i.e. ACR JIA30 response) [ Time Frame: At week 12 of treatment versus week 0 (pretreatment) ] [ Designated as safety issue: No ]
  • Efficacy of tocilizumab as defined by reduction of oral prednisone dose by at least 20%, or to less than 0.5mg/kg/day, whichever is of lesser daily dose, while maintaining an ACR JIA30 response [ Time Frame: At weeks 12 and 16 of treatment versus week 0 (pretreatment) ] [ Designated as safety issue: No ]
  • To evaluate the safety of tocilizumab administration in this subject [ Time Frame: Ongoing, throughout 24 month study period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess normalization of laboratory parameters of active disease, specifically C-reactive protein, hemoglobin, platelets, white blood cell count, ferritin, immunoglobulins. [ Time Frame: At weeks 8, 12, and 16 of treatment, and every 8-12 weeks thereafter ] [ Designated as safety issue: Yes ]
  • To assess sustained clinical response to tocilizumab, including active joint count, joints with limited range of motion, and absence of fever or rash. [ Time Frame: At weeks 8, 12, 16 of treatment, and every 8 weeks thereafter ] [ Designated as safety issue: No ]

Enrollment: 1
Study Start Date: March 2009
Study Completion Date: June 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab
Single arm study - treatment only
 Biological: tocilizumab

Initial therapy: Tocilizumab dosed by body weight (8mg/kg based on body weight ≥ 30kg) given by intravenous infusion every two weeks for 12 weeks.

Extension of therapy: Continuation of treatment with tocilizumab at 8mg/kg by body weight given by intravenous infusion every 2 weeks based upon achievement of Primary Objective by week 12, OR continuation of treatment with escalation of tocilizumab dose to 12mg/kg by body weight, given by intravenous infusion every two weeks, for failure to achieve ACR JIA30 at 12 weeks or ACR JIA50 response at any time after week 16.

Other Name: Actemra, RoACTEMRA, MRA

Detailed Description:

Systemic onset Juvenile Idiopathic Arthritis (soJIA) is a type of arthritis (inflammation of the joints) that occurs with other symptoms including fever, swollen lymph nodes (glands), rash, and body aches. Because soJIA can be difficult to treat, children with soJIA can have severe problems from long-term use of steroids (prednisone). These problems include low bone density (weak bones), fractures, failure to grow properly, and large weight gain. The arthritis that occurs in soJIA often causes damage to many joints. This can make it hard to move around or do basic tasks like dressing. Also, a life-threatening illness called Macrophage Activation Syndrome (MAS) can occur when starting, stopping, or changing drugs that are used to treat soJIA.

SoJIA can be hard to treat and many children with soJIA do not respond to drugs that work for other kinds of arthritis. Research doctors have studied a chemical signal called IL-6 that the body uses to manage inflammation. This signal has been found to be very high in patients with active soJIA. A drug called tocilizumab (TCZ) has been designed to block IL-6. For about 6 years, TCZ has been tested in Japan for treating soJIA. It is now being tested in studies in the United States. These studies can have very strict rules for enrolling patients. This trial is a single-patient research study for a subject who otherwise does not meet the rules for enrollment in ongoing trials.

  Eligibility

Ages Eligible for Study:   2 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Systemic Juvenile Idiopathic Arthritis according to ILAR criteria (2001)
  • Duration of disease ≥ 6 months since onset
  • Presence of active disease as determined by the presence of at least 5 active joints, OR at least 2 active joints if receiving prednisone at a dose > 0.2 mg/kg/day or > 10 mg/day (whichever is less)
  • Incomplete prior response to methotrexate treatment for at least 3 months at a minimum dose of 15 mg/M2/week, or intolerance to methotrexate
  • Discontinued treatment with other biologics prior to first tocilizumab infusion, for approximately two pharmacokinetic half-lives as per specific biologic (e.g. 48 hours for anakinra, 7 days for etanercept)
  • Not receiving corticosteroids, OR taking oral corticosteroids and the dose has remained stable for 1 week prior to the first tocilizumab infusion at ≤ 2 mg/kg/day prednisone or prednisolone and no more than 80 mg/day

Exclusion Criteria:

  • Concomitant administration of biologic therapies
  • Serum creatinine >1.5 ULN (upper limits normal)
  • AST or ALT > 1.5 ULN
  • Total bilirubin > 1.3 mg/dL
  • Platelet count < LLN (lower limits normal)
  • Hemoglobin < 6.0 g/dL
  • WBC count < 5,000/mm3
  • Neutrophil count < 2,000/ mm3
  • Fibrinogen < LLN
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00868751

Locations
United States, Massachusetts
Tufts Medical Center/Floating Hospital for Children
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts Medical Center
Hoffmann-La Roche
Investigators
Principal Investigator: Marc D Natter, MD Tufts Medical Center
  More Information

Additional Information:
A Study of Tocilizumab in Patients With Active Systemic Juvenile Idiopathic Arthritis  This link exits the ClinicalTrials.gov site

Publications:

Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT00868751     History of Changes
Other Study ID Numbers: TMC-PRHEU-TCZ-01
Study First Received: March 24, 2009
Last Updated: December 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Tufts Medical Center:
Antibodies, Monoclonal
Interleukin 6

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

ClinicalTrials.gov processed this record on May 19, 2013