Canakinumab for Treatment of Adult-onset Still's Disease

Study Protocol for a Multi-Centre, Placebo-Controlled Phase II Study of Canakinumab for the Treatment of Adult-onset Still's Disease (AOSD) Including an Open-label Long Term Extension

The purpose of this trial is to investigate the efficacy of the treatment with canakinumab in participants with Adult-onset Still's Disease (AOSD) and active joint involvement.

Inclusion Criteria:

1. Written and signed consent from the participant to take part in the study
2. Men and women aged ≥ 18 years and ≤ 75 years
3. Fulfilment of AOSD classification criteria (according to Yamaguchi et al, J. Rheumatology, 1992)
4. Disease activity based on Disease Activity Score 28 (DAS28) of ≥3.2 at screening
5. At least 4 painful and 4 swollen joints at screening and baseline (of the 28 joints according to DAS28)
6. If undergoing treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable dose for at least 4 weeks prior to randomisation
7. If undergoing treatment with glucocorticoids, stable dose of ≤10 milligrams per day (mg/day) (prednisolone or equivalent) for at least 4 weeks prior to randomisation
8. If undergoing treatment with conventional disease-modifying anti-rheumatic drugs (DMARD), stable dose for at least 3 months prior to randomisation
9. Normalisation period for biological DMARDS (anakinra 1 week, etanercept 1 month, adalimumab and certolizumab 2 months, infliximab, golimumab, abatacept and tocilizumab 3 months, rituximab 9 months, canakinumab 6 months) prior to randomisation
10. In participants of reproductive age, use of an effective method of contraception as well as negative pregnancy test prior to the study commencing.

Exclusion Criteria:

1. Previous treatment with the study drug with repeated administration of canakinumab
2. Intraarticular or intravenous administration of glucocorticoids within 4 weeks prior to the baseline or use of narcotic analgesics except for analgesics permitted within the framework of the investigation (codeine and tramadol)
3. Presence of another, serious chronic-inflammatory disease
4. Positive hepatitis B antigen (HBsAg), hepatitis C antibodies and/or human immunodeficiency virus (HIV) antibodies.
5. Presence of a relevant, active infection or other diseases, which entail a tendency towards infection
6. Positive screening for latent tuberculosis, in accordance with usual local practice
7. Raised liver count (raised bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3-fold the normal range)
8. Serum-creatinine concentration >1.5 milligrams per deciliter (mg/dL)
9. Inadequate haematological findings (hemoglobin [Hb] ≤ 10 grams per deciliter (g/dL), neutrophils ≤2,500/microliter (µl) and thrombocytes ≤100,000/µl)
10. Simultaneous participation in any other interventional clinical study within the last 30 days preceding the commencement of the study
11. History of neoplasia with the exception of a curatively treated non-melanoma skin tumour or carcinoma of the cervix treated in situ without any indication of recurrence within the last 10 years
12. Relevant cardiac or pulmonary disorders
13. Severe intercurrent neurological or psychiatric disorders
14. Macrophage activation syndrome (MAS) as part of previous treatment with IL-1 blockade (e.g. anakinra, rilonacept)
15. Vaccination with a live vaccine within 3 months before the baseline
16. Alcohol or drug abuse in the past 12 months
17. ≥400 milliliter (mL) donation of blood or loss up to 8 weeks before the baseline
18. Pregnancy or breast-feeding
19. Commitment of the patient to an institution at the direction of an authority or court