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.

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).

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.