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SYNOPSIS
Name of Sponsor/ Company
Chugai Pharmaceutical Co., Ltd.
Name of Finished Product
ACTEMRA
Name of Active Ingredient
tocilizumab
Title of Study
Investigators
Long-term Treatment Study of MRA in Patients with
Systemic Juvenile Idiopathic Arthritis
9 in total including Daiki Abukawa
9 in total including Dept. of General Paediatrics, Local
Study centre(s)
Incorporated Administrative Agency, Miyagi Children's
Hospital
Yokota S, Imagawa T, Mori M, Miyamae T, Aihara Y, Takei
Publication
（reference）
S, et al. 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.
Studied Period
（date of first enrolment）
8 July 2004 - 16 September 2008
(date of last complete)
Phase of development
Phase 3
Conducted as a Phase 4 study after marketing approval
To investigate the safety, efficacy and pharmacokinetics of
MRA when
administered
long-term in
the patients
investigated in the Early Phase II Study of MRA for
Objectives
Systemic Juvenile Idiopathic Arthritis (hereinafter "the
previous study: MRA011JP") and the Phase III Study of
MRA for Systemic Juvenile Idiopathic Arthritis (hereinafter
"the previous study: MRA316JP").
Methodology
MRA is administered at a dose of 8 mg/kg at two-week
intervals by intravenous infusion.
Number of patients
Planned number of patients: 55 patients
（planned and analysed ）
Full analysis set (FAS): 67 patients
Main inclusion criteria
MRA011JP patients
Diagnosis and main criteria
Of the patients who completed the previous study and were
for inclusion
currently in the extended treatment period, needed
continued treatment with MRA
MRA316JP patients
Patients to whom either of the following applied and who
required continued treatment with MRA
Patients who proceeded to the blind period and in whom the
last observations were performed after study completion or
withdrawal
Patients who received three infusions in the open-label
period and did not meet the criteria for transition to the
blind period but in whom CRP was lower than before the
start of the study as a result of treatment with MRA
Main exclusion criteria
Patients who had been treated with infliximab or etanercept
Other patients who are unsuitable for safety reasons
MRA Injection 200 mg (10 mL)
Lot Nos.: MR3K02, MR3K02A, MR5C05, MR5J02, MR6F01,
MR7G03
After marketing approval, the following postmarketing
Test product, dose and mode of
study drug is used.
administration, batch number
Actemra 200 mg for intravenous infusion
Lot Nos.: M8C23
Dose and Method of Administration: 8 mg/kg dose at each
infusion The interval between infusions was to be two
weeks.
Duration of treatment
The target is at least one year from the first infusion in
study
Reference therapy, dose and
mode of administration, batch
Not applicable
number
Efficacy:
Percentage of patients showing 30% improvement in the JIA
core set
Criteria for evaluation
Time course of percentage of patients showing 30%, 50%
and 70% improvement in the JIA core set
Time course of corticosteroid dose
Safety:
Efficacy
Statistical method
The percentage of patients showing 30% improvement in
the JIA core set
The time courses of the percentages of patients showing
30%, 50% and 70% improvement in the JIA core set
Time course of corticosteroid dose
Safety
Median age (range) was 8 years (2 to 19) and median
disease duration (range) was 3.8 years (0.4 to 16.2). Nine
patients discontinued tocilizumab treatment; 4 due to SAEs,
4 due to development of anti-tocilizumab antibodies, and
one due to lack of efficacy. Eight of the 9 patients
discontinued tocilizumab within 9 weeks of original study
starting. Median duration of tocilizumab treatment was 185
weeks (max. 324 weeks).
MRA treatment improved the JCR core set and the effects
were continued. The JCR core set30, 50, 70 and 90 were
achieved by 100%, 98%, 93%, and 64% of patients at Week
96 (N=58), and by 96%, 96%, 88%, and 73% of patients at
Summary - Conclusions
Week 168 (N=51), respectively.
At enrollment of the trials, all patients were under the
treatment with oral corticosteroids (median 11.6 mg
PSL-equivalent dose). During the long-term treatment, 77%
of them had reduced doses (< 50%) of corticosteroids at
Week 168. In the long-term therapy administration of
tocilizumab was ceased in 8 patients because of continuous
remission. Although 2 of the 8 patients sustained remission,
6 patients flared 7 to 82 weeks after the last infusion, and
resumed tocilizumab treatment.
Common adverse events were nasopharyngitis, upper
respiratory tract infection and gastroenteritis. No cases of
opportunistic
infections,
malignancies,
diseases, or death were reported.
Date of report
8 July 2011
autoimmune