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

Novartis Pharmaceuticals14 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Adult Onset Still's Disease

Interventions

CanakinumabBIOLOGICAL

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

Eligibility

Sex: ALLMin age: 16 YearsMax age: 100 Years

Medical Language ↔ Plain English

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.

Locations (9)

Novartis Investigative Site

Chiba, Chiba, Japan

Novartis Investigative Site

Sapporo, Hokkaido, Japan

Novartis Investigative Site

Yokohama, Kanagawa-ku, Japan

Novartis Investigative Site

Iruma-gun, Saitama, Japan

Outcomes

Primary Outcomes

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%: 1. Physicians global assessment of disease activity (PhGA) on a 0-100 mm visual analogue scale (VAS) (0=very good and 100=very poor). 2. Participant's assessment of disease activity (PtGA) on a 0-100 mm VAS (0=very good and 100=very poor). 3. 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). 4. Number of active joints (68 joints evaluated for pain/tenderness and 66 for swelling) 5. Index of inflammation: C-reactive Protein (CRP) levels Additionally, participants were required to have no intermittent fever during the preceding week.

Time frame: Baseline, Week 8

Secondary Outcomes

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: 1. PhGA \[0-100 VAS\] 2. PtGA \[0-100 VAS\] 3. HAQ-DI \[0-3 scale\] 4. Number of active joints (pain/tenderness: 0-68; swelling: 0-66) 5. CRP levels

Time frame: Baseline, Week 28

Number of Participants Who Achieved Adapted ACR 30 Response Criteria

Data from ClinicalTrials.gov

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Novartis Investigative Site

Bunkyo Ku, Tokyo, Japan

Novartis Investigative Site

Chuo Ku, Tokyo, Japan

Novartis Investigative Site

Mitaka, Tokyo, Japan

Novartis Investigative Site

Shinjuku-ku, Tokyo, Japan

Novartis Investigative Site

Ishikawa, Japan

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%: 1. Physicians global assessment of disease activity (PhGA) on a 0-100 mm VAS (0=very good and 100=very poor). 2. Participant's assessment of disease activity (PtGA) on a 0-100 mm VAS (0=very good and 100=very poor). 3. 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). 4. Number of active joints (68 joints evaluated for pain/tenderness and 66 for swelling) 5. Index of inflammation: C-reactive Protein (CRP) levels Additionally, participants were required to have no intermittent fever during the preceding week.