A Study to Evaluate Efficacy and Safety of Anakinra in the Treatment of Still's Disease (SJIA and AOSD)

A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Efficacy and Safety Study of 2 Dose Levels of Subcutaneous Anakinra (Kineret®) in Patients With Still's Disease (SJIA and AOSD)

The aim of this study is to demonstrate the efficacy and to evaluate the safety, pharmacokinetics (PK) and immunogenicity of anakinra in patients with newly diagnosed Still's disease, including SJIA (Systemic juvenile idiopathic arthritis) and AOSD (Adult-onset Still's disease).

The study consists of a 12-week, randomized, double-blind, placebo controlled period with two dose levels of anakinra and a 4-week safety follow-up after last dose of investigational medicinal product (IMP). The primary endpoint will be evaluated at Week 2. Sustained efficacy and time to study drug discontinuation will be evaluated during the full study period.

A screening visit is optional and may be done to identify patients that could be suitable for the study. During the study 6 visits and 2 telephone contacts are scheduled i.e., Day 1 (baseline visit), Day 4Tel, Week 1, Week 2, Week 4, Week 8, Week 12 and Week 16Tel (End of Study).

Patients will be randomly assigned to study drug, after they meet all of the inclusion criteria and none of the exclusion criteria. Patients will receive treatment for 12 weeks, either anakinra or placebo. Patients will be randomized to anakinra in a dose of either 2 or 4 mg/kg/day, with a maximum dose of 100 or 200 mg once daily, respectively. Patients will be randomized to placebo with corresponding volumes for each of the two anakinra dose levels.

Inclusion Criteria:

1. Signed informed consent.
2. Male and female patients with a body weight ≥ 10 kg.
3. Diagnosis of Still's disease.
4. If currently on glucocorticoid treatment, a stable dose for at least 1 week prior to randomization.
5. If currently on methotrexate treatment, a stable dose for at least 8 weeks prior to randomization.
6. Active disease.
7. Female patients of childbearing potential must use an effective method of contraception during the study (abstinence being a possible option) as well as present a negative pregnancy test prior to randomization.
8. Negative interferon-gamma release assay or Purified protein derivative ( PPD) test within 2 months prior to randomization. If not available, a test should be performed at day of randomization.

Exclusion Criteria:

1. Diagnosis of Still's disease more than 6 months prior to randomization.

2. Previous randomization into this study.

3. Participation in another concurrent clinical interventional study within 30 days of randomization.

4. Treatment with an investigational drug within 5 half-lives prior to randomization.

5. Previous or current treatment with anakinra, canakinumab or any other IL-1 inhibitor.

6. Use of the following therapies prior to randomization:

   • Narcotic analgesics within 24 hours prior to randomization.
   • Dapsone or etanercept within 3 weeks prior to randomization.
   • Intraarticular, intramuscular or intravenous administration of glucocorticoids or intravenous immunoglobulin (Ig) within 4 weeks prior to randomization.
   • Intravenous Ig with proven Still's disease modifying effect, leflunomide, infliximab or adalimumab within 8 weeks prior to randomization.
   • Thalidomide, cyclosporine, mycophenolate mofetil, 6-mercaptopurine, azathioprine, cyclophosphamide, chlorambucil or any other immunosuppressant within 12 weeks prior to randomization.
   • Tocilizumab within 12 weeks prior to randomization or any other immunomodulatory medication within 4 half-lives prior to randomization
   • Rituximab within 26 weeks prior to randomization.

7. Live vaccines within 1 month prior to randomization.

8. Known presence or suspicion of active, chronic or recurrent bacterial, fungal or viral infections, including tuberculosis, HIV infection or hepatitis B or C infection.

9. Clinical evidence of liver disease or liver injury.

10. Presence of severe renal function impairment.

11. Presence of neutropenia.

12. Presence or suspicion of MAS at baseline.

13. A diagnosis of MAS within the last 2 months prior to randomization.

14. History of malignancy within 5 years.

15. Known hypersensitivity to E coli-derived proteins, or any components of Kineret® (anakinra).

16. Pregnant or lactating women.

17. Foreseeable inability to cooperate with given instructions or study procedures.

18. Presence of any medical or psychological condition or laboratory result that in the opinion of the investigator can interfere with the patient's ability to comply with the protocol requirements or makes the patient not appropriate for inclusion to the study and treatment with IMP.