A Study of Anakinra in Japanese Patients With Still's Disease (SJIA and AOSD)

A study to demonstrate efficacy and safety of anakinra in pediatric and adult Japanese patients with Still's disease (Systemic juvenile idiopathic arthritis \[SJIA\] and Adult-onset Still's disease \[AOSD\]).

The study consists of two phases:

• Core phase comprising 2 weeks double blind placebo-controlled treatment, 52 weeks open label treatment and 4 weeks safety follow up (only for patients not entering the extension phase).

At the Week 54 visit, patients who consent and are eligible to continue anakinra treatment, will enter the extension phase and continue open label anakinra treatment.

• Extension phase comprising up to 26 weeks open label treatment and 4 weeks safety follow up.

The primary endpoint will be evaluated at Week 2 visit.

Eligibility Criteria:
Key Inclusion Criteria:

1. Male and female patients, 8 months of age or older with a body weight ≥ 10 kg
2. Diagnosis of Still's disease
3. If \< 16 years of age at disease onset, the diagnosis is madeaccording to adapted ILAR criteria i.e., CARRA criteria for SJIA. If ≥ 16 years of age at disease onset, the diagnosis is made according to Yamaguchi criteria for AOSD.
4. Active disease confirmed by the following three signs and symptoms. a. Active arthritis in ≥ 1 joint. b. CRP \> 30 mg/L. c. At least one fever episode (≥ 38.0 degree Celsius) attributable to the disease within one week before enrollment.
5. The result of tuberculosis test within 8 weeks prior to enrollment is negative.

Key Exclusion Criteria:

1. Previous or current treatment with anakinra, or any other Interleukin-1 (IL-1) inhibitor except for canakinumab. Previous treatment with canakinumab is allowed if canakinumab was discontinued for reasons other than lack of efficacy and after a washout period of minimum 130 days. Patients who have discontinued canakinumab because of insufficient effect or refractory disease are not allowed to be enrolled in the study.
2. Use of the following therapies prior to enrollment.

   1. Narcotic analgesics within 24 hours prior to enrollment.
   2. Diaminodiphenyl sulfone within 1 week prior to enrollment or etanercept within 2 weeks prior to enrollment.
   3. Intraarticular, intramuscular, or intravenous administration of glucocorticoids within 72h(3 days) prior to enrollment, or intravenous immunoglobulin within 4 weeks prior to enrollment.
   4. Intravenous immunoglobulins with proven Still's disease modifying effect, leflunomide, infliximab, or adalimumab within 8 weeks prior to enrollment.
   5. Thalidomide within 72h(3 days) prior to enrollment, cyclosporine within 5 weeks prior to enrollment, mycophenolate mofetil within 1 week prior to enrollment, 6-mercaptopurine within 48h(2 days) prior to enrollment, azathioprine within 72h(3 days) prior to enrollment, cyclophosphamide within 96h(4 days) prior to enrollment, chlorambucil (not approved inJapan) within 48h(2 days) prior to enrollment, or any other immunosuppressants within 12 weeks prior to enrollment.
   6. Tocilizumab within 4 weeks prior to enrollment or any other immunomodulatory medications within 4 half-lives prior to enrollment.
   7. Rituximab within 13 weeks prior to enrollment.
   8. Canakinumab within 130 days prior to enrollment
3. Live vaccines within 4 weeks prior to enrollment.
4. Known presence or suspicion of active, chronic, or recurrent bacterial, fungal, or viral infections, including but not limited to tuberculosis, HIV infection, Covid-19 infection, or hepatitis B or C infection at baseline. Patients with acute or chronic HBV.
5. Clinical evidence of liver disease or liver injury as indicated by presence of abnormal liver tests.
6. Presence of severe chronic kidney disease (CKD) grades 4 and 5.
7. Presence of neutropenia (absolute neutrophil count \[ANC\] \< 1.5 x 10\^9/L).
8. Presence of thrombocytopenia (platelets count \< 100 x 10\^9/L).
9. Presence or suspicion of MAS at baseline.
10. History or diagnosis of MAS within the last 4 weeks prior to enrollment.

After completion of the study Core Phase, patients who consent and are eligible to continue anakinra treatment, can enter the extension phase .