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

An Open-label, Single-arm, Active-treatment Study to Evaluate Efficacy and Safety of Canakinumab (ACZ885) Administered for at Least 48 Weeks in Japanese Patients With Adult Onset Still's Disease (AOSD)

This study was designed to evaluate the efficacy and safety of canakinumab administered subcutaneously every 4 weeks for at least 48 weeks in Japanese patients with Adult-Onset Still's Disease (AOSD).

Interim analysis data collected at Weeks 28 and 48 supported the registration submission of canakinumab for the indication of Adult Still's Disease (ASD) in Japan.

Study Overview

• Status: Completed
• Conditions: Adult Onset Still's Disease
• Intervention / Treatment: Biological: Canakinumab

Detailed Description

This was a Phase III, open-label, single-arm active treatment study designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics/pharmacodynamics (PK/PD) of canakinumab at a dose of 4 mg/kg (up to a maximum of 300 mg) administered subcutaneously every 4 weeks for at least 48 weeks in Japanese participants with ASD.

The study consisted of two epochs:

• Screening epoch: Day -28 to Day -1
• Open-label treatment epoch: Day 1 until either regulatory approval and commercial availability of canakinumab for adult Still's disease (ASD) in Japan, or study termination (whichever occurred first).

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Ishikawa, Japan, 9208641
    • Novartis Investigative Site
  • Chiba
    • Chiba, Chiba, Japan, 260 8677
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 0608648
      • Novartis Investigative Site
  • Kanagawa-ku
    • Yokohama, Kanagawa-ku, Japan, 236-0004
      • Novartis Investigative Site
  • Saitama
    • Iruma-gun, Saitama, Japan, 3500495
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo Ku, Tokyo, Japan, 1138655
      • Novartis Investigative Site
    • Chuo Ku, Tokyo, Japan, 1048560
      • Novartis Investigative Site
    • Mitaka, Tokyo, Japan, 181-8611
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 1608582
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent had to be obtained prior to participation in the study. Parent's or legal guardian's written informed consent and child's assent, if appropriate, were required before any assessment was performed for participants < 20 years of age.
• Japanese male and female participants aged ≥ 16 years were eligible.
• Diagnosis of AOSD had to be confirmed as per Yamaguchi criteria, with disease onset at ≥ 16 years of age. The Yamaguchi criteria required at least five criteria, including two major criteria and no exclusion criteria.
• Participants had to have active disease at baseline, defined as follows:
• Fever (body temperature > 38°C) due to AOSD for at least 1 day within 1 week before baseline
• At least 2 active joints (tender or swollen)
• CRP ≥ 10 mg/L

Exclusion Criteria:

• Pregnant or nursing (lactating) female participants were excluded. Pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL) at the screening visit.
• Participants with a history of significant hypersensitivity to the study drug or to biologics were excluded.
• Participants with a history or evidence of active macrophage activation syndrome or disseminated intravascular coagulation within 6 months prior to enrollment were excluded.
• Participants with underlying metabolic, renal, hepatic, infectious, or gastrointestinal conditions that, in the opinion of the investigator, compromised the participant and/or placed the participant at unacceptable risk for participation in immunomodulatory therapy were excluded.
• Participants with active or recurrent bacterial, fungal, or viral infections at the time of enrollment, including evidence of HIV infection, Hepatitis B, or Hepatitis C, were excluded.
• Participants with an absolute neutrophil count < 1500/mm³ at screening were excluded.

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: Canakinumab; All participants received canakinumab as open-label study medication. Canakinumab was administered subcutaneously at a dose of 4 mg/kg every four weeks, with a maximum allowable single dose of 300 mg.

Biological: Canakinumab; Canakinumab was provided as a 150 mg/1 mL solution for subcutaneous injection, administered at a dose of 4 mg/kg every four weeks. The medication was supplied by Novartis in individual 2 mL glass vials, each containing 150 mg of liquid canakinumab. Throughout the study, participants received subcutaneous injections of canakinumab 4 mg/kg (up to a maximum of 300 mg) at the study site every four weeks. Any participant who required a dose greater than a single dose of 150 mg (participants > 37.5 kg) received two s.c. injections per administration; Other Names: ACZ885

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Adapted American College of Rheumatology (ACR) 30 Response at Week 8	Adapted ACR30 response was defined as a ≥30% improvement from baseline in at least 3 of the following 5 core response variables, with no more than one of these variables worsening by >30%: Physicians global assessment of disease activity (PhGA) on a 0-100 mm visual analogue scale (VAS) (0=very good and 100=very poor).; Participant's assessment of disease activity (PtGA) on a 0-100 mm VAS (0=very good and 100=very poor).; Health Assessment Questionnaire- disability index (HAQ-DI): 20 questions across 8 domains assessing the functional abilities. The total score was calculated as the average of the scores for each domain, ranging from 0 (no disability) to 3 (very severe disability).; Number of active joints (68 joints evaluated for pain/tenderness and 66 for swelling); Index of inflammation: C-reactive Protein (CRP) levels Additionally, participants were required to have no intermittent fever during the preceding week.	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Were Able to Taper Corticosteroids Based on Success Criteria at Week 28.	Number of participants achieving successful corticosteroid tapering at Week 28 was assessed. Successful tapering was defined as meeting any one of the following criteria and maintaining a minimum Adapted ACR30 response: Participants with a baseline prednisone equivalent dose > 0.8 mg/kg/day must reduce to ≤ 0.5 mg/kg/day; Participants with a baseline dose between ≥ 0.5 and ≤ 0.8 mg/kg/day must reduce by ≥ 0.3 mg/kg/day; Participants with any baseline dose must reduce to ≤ 0.2 mg/kg/day; Participants with a baseline dose ≤ 0.2 mg/kg/day must achieve any reduction The Adapted ACR30 response requires ≥30% improvement in at least 3 of the following 5 variables, with no more than one worsening by >30%, and no intermittent fever in the preceding week: PhGA [0-100 VAS]; PtGA [0-100 VAS]; HAQ-DI [0-3 scale]; Number of active joints (pain/tenderness: 0-68; swelling: 0-66); CRP levels	Baseline, Week 28
Number of Participants Who Achieved Adapted ACR 30 Response Criteria	Adapted ACR30 response was defined as a ≥30% improvement from baseline in at least 3 of the following 5 core response variables, with no more than one of these variables worsening by >30%: Physicians global assessment of disease activity (PhGA) on a 0-100 mm VAS (0=very good and 100=very poor).; Participant's assessment of disease activity (PtGA) on a 0-100 mm VAS (0=very good and 100=very poor).; Health Assessment Questionnaire- disability index (HAQ-DI): 20 questions across 8 domains assessing the functional abilities. The total score was calculated as the average of the scores for each domain, ranging from 0 (no disability) to 3 (very severe disability).; Number of active joints (68 joints evaluated for pain/tenderness and 66 for swelling); Index of inflammation: C-reactive Protein (CRP) levels Additionally, participants were required to have no intermittent fever during the preceding week.	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Number of Participants Who Achieved Adapted ACR 50 Response Criteria	Adapted ACR50 response was defined as 50% reduction between baseline in at least 3 of the 5 response variables, with no more than one of these variables worsening by more than 30%: Physicians global assessment of disease activity on a 0-100 mm VAS (0=very good and 100=very poor).; Participant's assessment of disease activity (PtGA) on a 0-100 mm VAS (0=very good and 100=very poor).; Health Assessment Questionnaire- disability index (HAQ-DI): 20 questions across 8 domains assessing the functional abilities. The total score was calculated as the average of the scores for each domain, ranging from 0 (no disability) to 3 (very severe disability).; Number of active joints (68 joints evaluated for pain/tenderness and 66 for swelling); Index of inflammation: C-reactive Protein (CRP) levels Additionally, participants were required to have no intermittent fever during the preceding week.	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Number of Participants Who Achieved Adapted ACR 70 Response Criteria	Adapted ACR70 response was defined as 70% reduction between baseline in at least 3 of the 5 response variables, with no more than one of these variables worsening by more than 30%: Physicians global assessment of disease activity (PhGA) on a 0-100 mm VAS (0=very good and 100=very poor).; Participant's assessment of disease activity (PtGA) on a 0-100 mm VAS (0=very good and 100=very poor).; Health Assessment Questionnaire- disability index (HAQ-DI): 20 questions across 8 domains assessing the functional abilities. The total score was calculated as the average of the scores for each domain, ranging from 0 (no disability) to 3 (very severe disability).; Number of active joints (68 joints evaluated for pain/tenderness and 66 for swelling); Index of inflammation: C-reactive Protein (CRP) levels Additionally, participants were required to have no intermittent fever during the preceding week.	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Number of Participants Who Achieved Adapted ACR 90 Response Criteria	Adapted ACR90 response was defined as 90% reduction between baseline in at least 3 of the 5 response variables, with no more than one of these variables worsening by more than 30%: Physicians global assessment of disease activity (PhGA) on a 0-100 mm VAS (0=very good and 100=very poor).; Participant's assessment of disease activity (PtGA) on a 0-100 mm VAS (0=very good and 100=very poor).; Health Assessment Questionnaire- disability index (HAQ-DI): 20 questions across 8 domains assessing the functional abilities. The total score was calculated as the average of the scores for each domain, ranging from 0 (no disability) to 3 (very severe disability).; Number of active joints (68 joints evaluated for pain/tenderness and 66 for swelling); Index of inflammation: C-reactive Protein (CRP) levels Additionally, participants were required to have no intermittent fever during the preceding week.	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Number of Participants Who Achieved Adapted ACR 100 Response Criteria	Adapted ACR100 response was defined as 100% reduction between baseline in at least 3 of the 5 response variables, with no more than one of these variables worsening by more than 30%: Physicians global assessment of disease activity (PhGA) on a 0-100 mm VAS (0=very good and 100=very poor).; Participant's assessment of disease activity (PtGA) on a 0-100 mm VAS (0=very good and 100=very poor).; Health Assessment Questionnaire- disability index (HAQ-DI): 20 questions across 8 domains assessing the functional abilities. The total score was calculated as the average of the scores for each domain, ranging from 0 (no disability) to 3 (very severe disability).; Number of active joints (68 joints evaluated for pain/tenderness and 66 for swelling); Index of inflammation: C-reactive Protein (CRP) levels Additionally, participants were required to have no intermittent fever during the preceding week.	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Change From Baseline in Systemic Feature Score (SFS)	The SFS evaluated 10 features, each scored as 1 (present) or 0 (absent). The total score ranged from 0 (none present) to 10 (all present). A negative change from baseline indicated clinical improvement. Clinical features: Fever (>37.5°C for ≥5 consecutive days); Rash (salmon-pink during febrile episodes); Serositis; Lymphadenopathy (>1.5 cm); Hepatomegaly/splenomegaly (confirmed by ultrasound or palpation) Laboratory features: At baseline, considered present if: ESR ≥20 mm/hour; CRP ≥10 mg/L; WBC count ≥12×10⁹/L; Hemoglobin ≤11 g/dL; Platelets ≥400×10⁹/L During treatment and follow-up: ESR: 0 if <20 mm/hour or decreased ≥30%; 1 if increased or decreased <30%; CRP: 0 if <10 mg/L or decreased ≥30%; 1 if increased or decreased <30%; WBC count: 0 if <12×10⁹/L or decreased ≥20%; 1 if increased or decreased <20%; Hemoglobin: 0 if >11 g/dL or increased ≥20%; 1 if decreased or increased <20%; Platelets: 0 if <400×10⁹/L or decreased ≥20%; 1 if increased or decreased <20%	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Change From Baseline in the Component of Adapted ACR: Physician's Global Assessment of Disease Activity	The physician rated the participant's disease activity on a 0-100 mm VAS, ranging from no disease activity (0 mm) to very severe disease activity (100 mm). A negative change from baseline indicated improvement	aseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Change From Baseline in the Component of Adapted ACR: Patient's Global Assessment of Disease Activity	The participant's assessment of disease activity was assessed on the VAS. The VAS scale ranges from 0-100 mm, from no pain/very well (0 mm) to very severe pain/very poor (100 mm). A negative change from baseline indicated improvement	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Change From Baseline in the Component of Adapted ACR: Health Assessment Questionnaire- Disability Index (HAQ-DI)	The HAQ was used to assess physical ability and functional status of participants as well as quality of life. The disability dimension consisted of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing, arising, eating, walking, hygiene, reach, grip and usual activities. Each item is scored from 0 (no difficulty) to 3 (unable to do). The score for each domain is the highest item score, and the total score is the mean of the domain scores., ranging from 0 (no disability) to 3 (severe disability). A negative change from baseline indicated improvement.	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Change From Baseline in the Component of Adapted ACR: Number of Active Joints	Active joints were defined as joints with swelling or pain/tenderness. 68 joints were assessed for pain/tenderness and 66 joints for swelling. The number of active joints ranged from 0 (no active joints) to 68 (all joints tender and /or swollen). A negative change from baseline indicated improvement.	Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, End of Study (up to approx. 208 weeks)
Change From Baseline in the Component of Adapted ACR: C-Reactive Protein (CRP) Levels	CRP levels in the blood were determined A negative change from baseline indicated improvement in systemic inflammation	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Number of Participants With Absence of Intermittent Fever in the Preceding Week (Component of the Adapted ACR)	The number of participants without intermittent fever associated to AOSD (defined as oral, rectal, or axillary body temperature > 38°C only for several hours during the day) was assessed.	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Change From Baseline in Oral Corticosteroid Dose	The oral corticosteroid dose was derived from the prednisone equivalent dose per day. The change from baseline was assessed. A negative change from baseline indicated reduced corticosteroid use.	Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, End of Study visit (assessed up to approx. 208 weeks)
Number of Participants With or Without Rash (Typical vs. Atypical)	The absence or presence of skin rash was assessed based on physical exam findings including whether it is typical or/and atypical. Participants with a rash showing both typical and atypical features were counted in both sub-categories. In the summary table, for each visit participants are classified as: rash present (typical and/or atypical), rash present (typical), rash present (atypical), or rash absent. For every visit, the denominator used to calculate percentages corresponds to the number of participants with available data at that visit.	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Change From Baseline in Disease Activity Score (DAS)28 - CRP	DAS28-CRP was a composite index validated for patients with rheumatoid arthritis (RA). It took into account the following components: tender joint count (0-28), swollen joint count (0-28), C-reactive protein (CRP, mg/L), and the Patient's Global Assessment of Disease Activity (Global Health), rated from 0 (best) to 100 (worst). These results were combined to produce the DAS28-CRP score, which ranged from 1.0 (disease remission) to 9.4 (high disease activity). A negative change from baseline in DAS28-CRP indicated an improvement	Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks)
Canakinumab Concentrations Over Time	Serum canakinumab concentrations by visit	Baseline (pre-dose), Day 3, Day 15, and pre-dose at Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192.
Total IL-1β Levels	Total IL-1β (sum of IL-1β free and bound to canakinumab) in serum was assessed	Baseline (pre-dose), Day 3, Day 15, and pre-dose at Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192.
Number of Participants With Canakinumab Anti-drug Antibodies (ADA)	The ADAs against canakinumab were assessed in serum using a validated immunoassay assay. The number of participants who had a canakinumab ADA positive result was assessed	Pre-dose at baseline, Weeks 24, 48, 72, 96, 120, 144

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Actual): April 16, 2025
• Study Completion (Actual): April 16, 2025

Study Registration Dates

• First Submitted: December 18, 2020
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Japanese participants; Canakinumab; AOSD; IL-1β
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis, Rheumatoid; Skin and Connective Tissue Diseases; Still's Disease, Adult-Onset; canakinumab
• Other Study ID Numbers: CACZ885G1302; 2021-003706-50 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No