Study of Efficacy and Safety of Canakinumab in Japanese Patients With SJIA

An Open-label, Single-arm, Active-treatment, Efficacy and Safety Study of Canakinumab (ACZ885) Administered for at Least 48 Weeks in Japanese Patients With Systemic Juvenile Idiopathic Arthritis (SJIA)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02396212

Enrollment

Registered

2015-03-24

Start date

2015-05-07

Completion date

2018-08-01

Last updated

2019-09-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Systemic Juvenile Idiopathic Arthritis

Keywords

ACZ885, canakinumab, Juvenile Rheumatoid arthritis (JRA) chronic, systemic inflammatory disorder, painful joints, inflammation of the synovial membrane, auto-immune rheumatoid disease, reactive rheumatoid arthritis, Systemic Juvenile Rheumatoid arthritis (SJRA), Japanese patients

Brief summary

This was a phase III study designed to provide efficacy and safety data for canakinumab administered for at least 48 weeks as subcutaneous (s.c.) injection every 4 weeks (q4wk) in Japanese patients with Systemic Juvenile Idiopathic Arthritis (SJIA). Interim analysis (IA) data at Week 28 and 48 from this study supported a registration submission of canakinumab in the indication of SJIA in Japan.

Interventions

BIOLOGICALCanakinumab

canakinumab was provided as a 150 mg/1 mL solution for subcutaneous injection and administered at 4mg/kg every 4 weeks.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

2 Years to 19 Years

Healthy volunteers

Inclusion criteria

\- Confirmed diagnosis of SJIA as per International League Against Rheumatism (ILAR) definition (Petty, et al. 2004) that must have occurred at least 3 months prior to enrollment with an onset of disease \< 16 years of age: Arthritis in one or more joints, with or preceded by fever of at least 2 weeks duration that is documented to be daily/quotidian for at least 3 days and accompanied by one or more of the following: Rash due to SJIA, lymphadenopathy, Hepatomegaly/Splenomegaly, Serositis * Active disease at the time of baseline defined as follows: * At least 2 joints with active arthritis * Documented spiking, intermittent fever (body temperature \> 38°C) for at least 1 day during the screening epoch and within 1 week before first canakinumab dose * C-Reactive Protein (CRP) \> 30 mg/L(3 mg/dL) (normal range \< 10 mg/L(1 mg/dL)) * Negative TB screen (Chest X-ray and T-SPOT test)

Exclusion criteria

* With active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infection. Patients with resolved/previous hepatitis B infection (a negative HBs antigen, but a positive anti-HBs antibody and/or anti-HBc antibody). * With underlying metabolic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and /or places the patient at unacceptable risk for participation. * With neutropenia (absolute neutrophil count \< 1500/mm3) at screening.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Achieved a Minimum Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria	Week 8	Minimum Adapted ACR Pediatric 30 criteria is defined as improvement from baseline at least 30% in at least 3 of response variables 1 to 6 in Adapted ACR Pediatric response variables and no intermittent fever (i.e. axillary, oral, or rectal body temperature ≤ 38°C) in the preceding week (variable 7), with no more than one variable 1-6 worsening by more than 30%. Adapted ACR Pediatric response variables consists of following 7 variables: 1. Physician's Global Assessment of disease activity on a 0-100 mm VAS; 2. Parent's or Patient's (if appropriate in age) Global Assessment of Patient's overall wellbeing based upon the 0-100 mm VAS in the Child Health Assessment Questionnaire (CHAQ); 3. Functional ability: CHAQ; 4. Number of joints with active arthritis; 5. Number of joints with limitation of motion; 6. Laboratory measure of inflammation: CRP (mg/L); 7. Absence of intermittent fever due to SJIA during the preceding week.
Percentage of Participants With Canakinumab Treatment Who Were Able to Taper Corticosteroids Successfully	Week 28	To evaluate the percentage of participants with canakinumab treatment who were able to taper corticosteroids successfully at Week 28

Secondary

Measure	Time frame	Description
Serum Concentration of Canakinumab	Baseline, Weeks 4, 24, 48, 72, 96, EOS (up to Week 164)	To evaluate serum concentration (mean, standard deviation) of canakinumab.
Pharmacodynamics (PD) Assessment: Total IL-1 Beta	Baseline, Weeks 4, 24, 48, 72, 96, EOS (up to Week 164)	To evaluate serum total IL-1 Beta concentration by visit.
Percentage of Participants Who Met the Adapted ACR Pediatric 30/50/70/90/100 Criteria of Canakinumab Over Time	Weeks 4, 8, 28, 48, 96, 144, end of study (EOS) (up to Week 164)	Adapted ACR Pediatric 30/50/70/90/100 criteria was assessed based on the following 7 variables: 1. Physician's Global Assessment of disease activity on a 0-100 mm VAS; 2. Parent's or Patient's (if appropriate in age) Global Assessment of Patient's overall wellbeing based upon the 0-100 mm VAS in the CHAQ; 3. Functional ability: CHAQ; 4. Number of joints with active arthritis; 5. Number of joints with limitation of motion; 6. Laboratory measure of inflammation: CRP (mg/L); 7. Absence of intermittent fever due to SJIA during the preceding week. Response was defined as more than or equal to (≥) 30%/50%/70%/90% or 100% improvement in at least 3 of 6 response variables and no intermittent fever in the preceding week (variable 7) with no more than one variable 1-6 worsening by more than 30%.
Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Physician's Global Assessment of Disease Activity	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)	ACR component, Physician's Global Assessment of disease activity on a 0 - 100 mm VAS by visit is the first response ACR variable in the ACR pediatric criteria. The VAS scale ranges from no disease activity (0 mm) to very severe disease activity (100 mm). Lower scale indicates decreased disease activity. Change from baseline was calculated by subtracting baseline value from post baseline value.
Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: CHAQ: Parent's or Patient's Global Assessment of Patient's Overall Well-being as Part of CHAQ	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS up to Week 164	ACR component, Parent's or Patient's (if appropriate in age)Global Assessment of patient's overall well-being as part of CHAQ on a 0 - 100 mm VAS by visit is the second response variable in the ACR pediatric criteria. The VAS scale ranges from 0-100 mm, from very well (0 mm) to very poor (100 mm). Lower scale indicates improvement of patient's overall well-being. Absolute change is calculated by subtracting baseline value from post baseline value.
Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: CHAQ: Functional Ability Score	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)	Disability Score as part of CHAQ per functional ability score (range from 0 to 3) is one of the variable in the ACR ped criteria. The CHAQ was used to assess physical ability & functional status of patients as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activity categories of daily living: dressing & grooming, arising, eating, walking, reaching, personal hygiene, gripping & other activities. Subjects choose from 4 responses, ranging from 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) & 3 (unable to do). Standard Disability Index (SDI) was computed by summing up the computed scores for each activity category and dividing by the number of categories answered. The lower the response the more positive the results & the higher the response, the less positive the results. Change from baseline was calculated by subtracting baseline value from post baseline value.
Percentage of Participants With Canakinumab Treatment Who Were Able to Taper Corticosteroids Successfully Over Time	Weeks 28, 48, 96, 144, EOS (up to Week 164)	To evaluate the percentage of participants with canakinumab treatment who were able to taper corticosteroids successfully over time
Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Number of Joints With Limitation of Motion	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)	ACR component, Number of joints with limitation of motion is the fifth response variable in the ACR ped criteria.
Number of Participants Having Fever in the Adapted ACR Pediatric Criteria of Canakinumab Over Time	Baseline, Day 3, Weeks 2, 8, 28, 48, 56, 96, 124, 144, EOS (up to Week 164)	ACR component, Number of participants having fever is the seventh response variable in the ACR ped criteria.
Percentage Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Standardized C-Reactive Protein (CRP)	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)	ACR component, Standardized CRP is the sixth response variable in the ACR ped criteria. CRP values were standardized to a normal range of 0 to 10 mg/L.
Percentage of Participants Who Had Flares With Canakinumab Treatment Over Time	> Day3, to <= Week 124	Flare was defined by at least 1 of the following: Reappearance of SJIA-related (e.g., not due to infection) fever (\> 38°C) lasting for at least 2 consecutive days &/OR Flare according to the JIA pediatric criteria for flare (all criteria must be met): ≥ 30% worsening in at least 3 of the 6 response variables and ≥ 30% improvement in at not more than 1 of the 6 response variables if the physician's or parent's global assessment is 1of 3 response variables used to define flare, worsening of ≥ 20 mm must be present, if the number of active joints or joints with limitation of motion is one of 3 response variables used to define flare, worsening in ≥ 2 joints must be present if CRP is used to define flare, CRP must be \> 30 mg/L
Percentage of Participants Who Achieved Inactive Disease (With and Without Duration of Morning Stiffness) With Canakinumab Treatment Over Time	Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)	Inactive disease was defined as meeting all of the following: No joints with active arthritis; No fever (body temperature ≤ 38°C); No rheumatoid rash, serositis, splenomegaly, hepatomegaly or generalized lymphadenopathy attributable to JIA; Normal CRP; Physician's global assessment of disease activity score ≤ 10 mm
Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Number of Joints With Active Arthritis	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)	ACR component, Number of joints with active arthritis was assessed as the forth response variables of ACR Pediatric Criteria.
Absolute Change From Baseline of Corticosteroids Dose Reduction With Canakinumab Treatment Over Time	Baseline, Weeks 28, 48, 96, 144, EOS (up to Week 164)	To evaluate the change from baseline of corticosteroids dose reduction with canakinumab treatment over time

Countries

Japan

Participant flow

Recruitment details

It was planned to enroll approximately 20 patients in this study. There were19 patients enrolled and data from all patients were analyzed.

Participants by arm

Arm	Count
Canakinumab 4 mg/kg Every 4 Weeks All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.	19
Total	19

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Lack of Efficacy	2

Baseline characteristics

Characteristic	Canakinumab 4 mg/kg Every 4 Weeks
Age, Continuous	9.9 Years STANDARD_DEVIATION 4.47
Race/Ethnicity, Customized Asian	19 Participants
Sex: Female, Male Female	13 Participants
Sex: Female, Male Male	6 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 19
other Total, other adverse events	19 / 19
serious Total, serious adverse events	10 / 19

Outcome results

Primary

Percentage of Participants Who Achieved a Minimum Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria

Minimum Adapted ACR Pediatric 30 criteria is defined as improvement from baseline at least 30% in at least 3 of response variables 1 to 6 in Adapted ACR Pediatric response variables and no intermittent fever (i.e. axillary, oral, or rectal body temperature ≤ 38°C) in the preceding week (variable 7), with no more than one variable 1-6 worsening by more than 30%. Adapted ACR Pediatric response variables consists of following 7 variables: 1. Physician's Global Assessment of disease activity on a 0-100 mm VAS; 2. Parent's or Patient's (if appropriate in age) Global Assessment of Patient's overall wellbeing based upon the 0-100 mm VAS in the Child Health Assessment Questionnaire (CHAQ); 3. Functional ability: CHAQ; 4. Number of joints with active arthritis; 5. Number of joints with limitation of motion; 6. Laboratory measure of inflammation: CRP (mg/L); 7. Absence of intermittent fever due to SJIA during the preceding week.

Time frame: Week 8

Population: The Full Analysis Set (FAS) consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm	Measure	Value (NUMBER)
Canakinumab 4 mg/kg Every 4 Weeks	Percentage of Participants Who Achieved a Minimum Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria	100.0 Percentage of Participants

Primary

Percentage of Participants With Canakinumab Treatment Who Were Able to Taper Corticosteroids Successfully

To evaluate the percentage of participants with canakinumab treatment who were able to taper corticosteroids successfully at Week 28

Time frame: Week 28