Single Patient Use of Tocilizumab in Systemic Onset Juvenile Idiopathic Arthritis

Single Patient Use of Tocilizumab for Treatment of Steroid Dependent, Active Systemic Onset Juvenile Idiopathic Arthritis

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.

Study Overview

• Status: Terminated
• Conditions: Arthritis, Juvenile Rheumatoid; Still's Disease, Juvenile Onset
• Intervention / Treatment: Biological: tocilizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center/Floating Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: Actemra, RoACTEMRA, MRA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)		At week 12 of treatment versus week 0 (pretreatment)
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		At weeks 12 and 16 of treatment versus week 0 (pretreatment)
Number of Participants With at Least One Adverse Event	To evaluate the safety of tocilizumab administration in this subject	Ongoing, throughout 24 month study period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Laboratory Parameters of Active Disease, Specifically C-reactive Protein, Hemoglobin, Platelets, White Blood Cell Count, Ferritin, Immunoglobulins.	To assess normalization of laboratory parameters of active disease, specifically C-reactive protein, hemoglobin, platelets, white blood cell	At weeks 8, 12, and 16 of treatment, and every 8-12 weeks thereafter
Measurement of Sustained Clinical Response to Tocilizumab, Including Active Joint Count, Joints With Limited Range of Motion, and Absence of Fever or Rash.	To assess sustained clinical response to tocilizumab, including active joint count, joints with limited range of motion, and absence of fever	At weeks 8, 12, 16 of treatment, and every 8 weeks thereafter

Collaborators and Investigators

• Sponsor: Tufts Medical Center
• Collaborators: Hoffmann-La Roche
• Investigators: Principal Investigator: Marc D Natter, MD, Tufts Medical Center

Publications and helpful links

General Publications

• Yokota S, Imagawa T, Mori M, Miyamae T, Aihara Y, Takei S, Iwata N, Umebayashi H, Murata T, Miyoshi M, Tomiita M, Nishimoto N, Kishimoto T. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. 2008 Mar 22;371(9617):998-1006. doi: 10.1016/S0140-6736(08)60454-7.

Helpful Links

• A Study of Tocilizumab in Patients With Active Systemic Juvenile Idiopathic Arthritis

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: March 24, 2009
• First Submitted That Met QC Criteria: March 24, 2009
• First Posted (Estimate): March 25, 2009

Study Record Updates

• Last Update Posted (Actual): May 15, 2017
• Last Update Submitted That Met QC Criteria: May 9, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Interleukin 6; Antibodies, Monoclonal
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Juvenile
• Other Study ID Numbers: TMC-PRHEU-TCZ-01