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

Systemic Juvenile Idiopathic Arthritis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02396212
• Other study ID #: CACZ885G1301
• Secondary ID: 2018-002355-15
• Status: Completed
• Phase: Phase 3
• Start date: May 7, 2015
• Est. completion date: August 1, 2018

Study information

• Verified date: August 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: August 1, 2018
• Est. primary completion date: March 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 19 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Systemic Juvenile Idiopathic Arthritis

Intervention

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

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Chiba-city	Chiba
Japan	Novartis Investigative Site	Kagoshima city	Kagoshima
Japan	Novartis Investigative Site	Kanazawa-city	Ishikawa
Japan	Novartis Investigative Site	Obu	Aichi
Japan	Novartis Investigative Site	Sendai-city	Miyagi
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Week 8
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	Week 28
Secondary	Percentage of Participants Who Met the Adapted ACR Pediatric 30/50/70/90/100 Criteria of Canakinumab Over Time	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%.	Weeks 4, 8, 28, 48, 96, 144, end of study (EOS) (up to Week 164)
Secondary	Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Physician's Global Assessment of Disease Activity	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.	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)
Secondary	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	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.	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS up to Week 164
Secondary	Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: CHAQ: Functional Ability Score	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.	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)
Secondary	Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Number of Joints With Active Arthritis	ACR component, Number of joints with active arthritis was assessed as the forth response variables of ACR Pediatric Criteria.	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)
Secondary	Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Number of Joints With Limitation of Motion	ACR component, Number of joints with limitation of motion is the fifth response variable in the ACR ped criteria.	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)
Secondary	Number of Participants Having Fever in the Adapted ACR Pediatric Criteria of Canakinumab Over Time	ACR component, Number of participants having fever is the seventh response variable in the ACR ped criteria.	Baseline, Day 3, Weeks 2, 8, 28, 48, 56, 96, 124, 144, EOS (up to Week 164)
Secondary	Percentage Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Standardized C-Reactive Protein (CRP)	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.	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)
Secondary	Percentage of Participants Who Had Flares With Canakinumab Treatment Over Time	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	> Day3, to <= Week 124
Secondary	Percentage of Participants Who Achieved Inactive Disease (With and Without Duration of Morning Stiffness) With Canakinumab Treatment Over Time	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	Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)
Secondary	Percentage of Participants With Canakinumab Treatment Who Were Able to Taper Corticosteroids Successfully Over Time	To evaluate the 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)
Secondary	Absolute Change From Baseline of Corticosteroids Dose Reduction With Canakinumab Treatment Over Time	To evaluate the change from baseline of corticosteroids dose reduction with canakinumab treatment over time	Baseline, Weeks 28, 48, 96, 144, EOS (up to Week 164)
Secondary	Serum Concentration of Canakinumab	To evaluate serum concentration (mean, standard deviation) of canakinumab.	Baseline, Weeks 4, 24, 48, 72, 96, EOS (up to Week 164)
Secondary	Pharmacodynamics (PD) Assessment: Total IL-1 Beta	To evaluate serum total IL-1 Beta concentration by visit.	Baseline, Weeks 4, 24, 48, 72, 96, EOS (up to Week 164)