The objective of this study is to assess safety, tolerability and early signs of efficacy of the investigational drug Tadekinig alfa in Adult-onset Still's disease, a rare polygenic auto-inflammatory disorder for which treatment remains empirical.

This disease is characterized by a daily spiking fever, arthralgia / arthritis, and skin rashes with frequent components of sore throat, lymphadenopathies and neutrophilic leukocytosis. The etiology is unknown. In addition to the above-mentioned clinical features, the diagnosis includes some laboratory components that reflect the systemic inflammation: high erythro-sedimentation rate, C-reactive protein, high serum ferritin and high levels of interleukin 18 (IL-18).

Tadekinig alfa is the drug name for recombinant human interleukin-18 binding protein (IL-18BP). This investigational drug was tested in healthy volunteers, psoriasis and rheumatoid arthritis patients in phase I studies. It demonstrated good safety and tolerability profile with only mild adverse events in the injection site.

The hypothesis of this study considers high levels of IL-18 during active Adult-onset still's disease as the therapeutic target. Treatment with IL-18BP will permit to inhibit the pro-inflammatory cascade triggered by IL-18 and may help to manage the different components of the disease.

This study is an open label, dose-finding study involving multiple centers in Europe. Two dose cohorts (80mg and 160mg) were treated during twelve weeks and followed-up for four more weeks.

Inclusion Criteria:

• Patients aged 18 years and older, diagnosed as AoSD based on the presence of the Yamaguchi criteria with active disease (see appendix 2), irrespective of the continuation of the permitted treatment mentioned below
• Patients with active disease will be considered if they exhibit at least two of the Yamaguchi's major criteria (see appendix 2) at the screening visit plus at least either fever or elevation of markers of inflammation (CRP ≥ 10 mg/L).
• Patients that have been exposed to NSAIDS, Prednisone (at least 5mg/day for ≥1 month) and/or synthetic sDMARDs (methotrexate at a dose of at least 10mg/day for ≥ 3 months) without response to treatment or with incomplete response to treatment
• Women of childbearing potential with negative pregnancy test at screening, V3, V4, V5 and V6 and that agree to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment. Birth control methods that are considered as highly effective are either: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence.

In each case of delayed menstrual period (over one month between menstruations, confirmation of absence of pregnancy is strongly recommended. This recommendation also applies to women of child bearing potential with infrequent or irregular menstrual cycles.

As regards the duration of contraception after the study, taking into account the median half-life of Tadekinig alfa of almost 40h, 5 half-lives represent duration of 200 hours. In order to be on the safe side, a post-study contraception duration of - Patients can maintain treatment with stable doses of Non-Steroidal anti-inflammatory Drugs (NSAIDs), Prednisone (stable dose of Prednisone of at least 5mg/day), and sDMARDs during Tadekinig alfa treatment (methotrexate at a dose of at least 10mg/week). Specifically baseline levels of prednisone treatment can be maintained or tapered (due to patient improvement), any requirement for prednisone increase during treatment will be considered a treatment failure.

• Ability to understand and willingness to sign a written informed consent
• Previous treatments with biologicals are allowed if the following wash-out periods are respected: one week for anakinra, two weeks for etanercept, and 6 weeks for, adalimumab, certolizumab, golimumab, tocilizumab, abatacept and 8 weeks for infliximab. Previous rituximab administration will require 6 months of washout and normal B-cell counts and previous treatment with canakinumab will require 6 months of washout.

Exclusion Criteria:

• Patients with a first episode of AoSD with less than one month of therapy with Prednisone or sDMARDs
• Patients with active or chronic infections (i.e. Tuberculosis (TB), HIV, HBV & HCV)
• Patients suffering from inherited immunodefinciency diseases
• Patients suffering from immune-mediated inflammatory diseases, including RA, SLE, etc. or spondylarthropathies, or inflammatory bowel disease.
• Patients with white blood cell counts below 2'500 cells/mm3
• Concomitantly treated with biologicals
• Women of childbearing potential who are unwilling to use highly effective birth control methods (see definition in Inclusion criteria above) up to 1 month after the end of her participation in the study.
• Inability to understand and unwilling to sign a written informed consent
• Any acute or chronic life-threatening disease: Such as cancer, and irreversible organ failures of heart, liver, lung and kidney (creatinine not higher than 1.5 X upper limit of normal).
• Patients having received adalimumab, certolizumab, golimumab, tocilizumab, abatacept within 6 weeks, infliximab within 8 weeks, canakinumab within 6 months, etanercept within 2 weeks, or anakinra 1 week prior to the start of Tadekinig alfa will not be enrolled into the study. Patients that have received rituximab within 6 months and/or have persistent low B-cell counts will not be eligible for enrolment.
• Subject who cannot be expected to comply with the study procedures
• Currently participating or having participated in another clinical trial during the last 4 weeks prior to the beginning of this study.
• Patients with no social security coverage
• Patients with a history of severe hypersensitivity reactions