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Active, Not Recruiting

NCT Number: NCT05814159

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]).

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Still's Disease, Juvenile Onset Arthritis Arthritis, Juvenile Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases Still's Disease, Adult-Onset

Age range

8 month and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Fukushima Medical University Hospital, Fukushima, Japan

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Male and female patients, 8 months of age or older with a body weight ≥ 10 kg
  • Diagnosis of Still's disease
  • 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.
  • 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.
  • The result of tuberculosis test within 8 weeks prior to enrollment is negative.

Key Exclusion Criteria:

  • 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.
  • Use of the following therapies prior to enrollment.
  • Narcotic analgesics within 24 hours prior to enrollment.
  • Diaminodiphenyl sulfone within 1 week prior to enrollment or etanercept within 2 weeks prior to enrollment.
  • Intraarticular, intramuscular, or intravenous administration of glucocorticoids within 72h(3 days) prior to enrollment, or intravenous immunoglobulin within 4 weeks prior to enrollment.
  • Intravenous immunoglobulins with proven Still's disease modifying effect, leflunomide, infliximab, or adalimumab within 8 weeks prior to enrollment.
  • 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.
  • Tocilizumab within 4 weeks prior to enrollment or any other immunomodulatory medications within 4 half-lives prior to enrollment.
  • Rituximab within 13 weeks prior to enrollment.
  • Canakinumab within 130 days prior to enrollment
  • Live vaccines within 4 weeks prior to enrollment.
  • 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.
  • Clinical evidence of liver disease or liver injury as indicated by presence of abnormal liver tests.
  • Presence of severe chronic kidney disease (CKD) grades 4 and 5.
  • Presence of neutropenia (absolute neutrophil count [ANC] < 1.5 x 10^9/L).
  • Presence of thrombocytopenia (platelets count < 100 x 10^9/L).
  • Presence or suspicion of MAS at baseline.
  • 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 .

Treatment and study plan

Anakinra

Drug

sub cutaneous daily injection

Other names: Kineret

Placebo

Drug

sub cutaneous daily injection

Primary outcomes

  1. An improvement of ≥ 30% from baseline in physician global assessment of disease activity (visual analogue scale [VAS]).

    Time frame: Week 2

    ACR30 response with absence of fever attributable to the disease during the 7 days

  2. An improvement of ≥ 30% from baseline in patient/parent global assessment of overall well-being (VAS).

    Time frame: Week 2

    ACR30 response with absence of fever attributable to the disease during the 7 days

  3. An improvement of ≥ 30% from baseline in number of joints with active arthritis.

    Time frame: Week 2

    ACR30 response with absence of fever attributable to the disease during the 7 days

  4. An improvement of ≥ 30% from baseline in number of joints with limitation of motion.

    Time frame: Week 2

    ACR30 response with absence of fever attributable to the disease during the 7 days

  5. An improvement of ≥ 30% from baseline in assessment of physical function: Child health assessment questionnaire (CHAQ)/Stanford health assessment questionnaire (SHAQ).

    Time frame: Week 2

    ACR30 response with absence of fever attributable to the disease during the 7 days

  6. An improvement of ≥ 30% from baseline in C-reactive protein (CRP) (mg/L).

    Time frame: Week 2

    ACR30 response with absence of fever attributable to the disease during the 7 days

Secondary outcomes

  1. Change in CRP.

    Time frame: Week 2

    To demonstrate the efficacy of anakinra compared to placebo in reducing inflammation in Still's disease.

  2. Change in ferritin.

    Time frame: Week 2

    To demonstrate the efficacy of anakinra compared to placebo in reducing inflammation in Still's disease.

  3. Change in haemoglobin.

    Time frame: Week 2

    To demonstrate the efficacy of anakinra compared to placebo in reducing inflammation in Still's disease.

  4. Change in platelets count.

    Time frame: Week 2

    To demonstrate the efficacy of anakinra compared to placebo in reducing inflammation in Still's disease.

  5. Change in white blood cells count.

    Time frame: Week 2

    To demonstrate the efficacy of anakinra compared to placebo in reducing inflammation in Still's disease.

  6. Absence of fever during the 24 hours preceding the evaluation visit at Week 1.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  7. Absence of rash during the 24 hours preceding the evaluation visit at Week 1.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  8. ACR30 response with absence of fever during the 24 hours preceding the evaluation visit at Week 1.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  9. ACR50 response with absence of fever during the 24 hours preceding the evaluation visit at Week 1.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  10. ACR70 response with absence of fever during the 24 hours preceding the evaluation visit at Week 1.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  11. Change in physician global assessment of disease activity, measured on a VAS from no pain (0 mm) to very severe (100 mm).

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  12. Change in patient/parent global assessment of overall well-being, measured on a VAS from no pain (0 mm) to very severe (100 mm).

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  13. Change in patient/parent global assessment of disease related pain, measured on a VAS from no pain (0 mm) to very severe (100 mm).

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  14. Change in swelling joints count.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  15. Change in tender joints count.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  16. Change in CRP.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  17. Change in ferritin.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  18. Change in haemoglobin.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  19. Change in platelets count.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  20. Change in white blood cells count.

    Time frame: Week 1

    To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.

  21. Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y Proxy (4-7 years).

    Time frame: Week 2

    To evaluate and compare the health status between anakinra treated patients and patients treated with placebo.

  22. Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y (8-15 years).

    Time frame: Week 2

    To evaluate and compare the health status between anakinra treated patients and patients treated with placebo.

  23. Change in the number/proportion of patients reporting problems by dimension of EQ-5D-3L (≥ 16 years).

    Time frame: Week 2

    To evaluate and compare the health status between anakinra treated patients and patients treated with placebo.

  24. Absence of fever during the 7 days preceding the visit.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  25. Absence of rash during the 7 days preceding the visit.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  26. ACR30 response with absence of fever during the 7 days preceding the visit.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  27. ACR50 response with absence of fever during the 7 days preceding the visit.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  28. ACR70 response with absence of fever during the 7 days preceding the visit.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  29. ACR90 response with absence of fever during the 7 days preceding the visit.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  30. Change in physician global assessment of disease activity (VAS).

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  31. Change in patient/parent global assessment of overall well-being (VAS).

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  32. Change in patient/parent global assessment of disease related pain (VAS).

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  33. Change in swelling joints count.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  34. Change in tender joints count.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  35. Change in CRP.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  36. Change in ferritin.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  37. Change in haemoglobin.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  38. Change in platelets count.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  39. Change in white blood cells count.

    Time frame: Week 4 to Week 54

    To evaluate efficacy of anakinra in Still's disease.

  40. Occurrence of inactive disease.

    Time frame: Week 8 to Week 54

    Proportion of patients who reach inactive disease.Inactive disease is defined as no joints with active arthritis, no fever, no rash, serositis, no hepatosplenomegaly, no generalized lymphadenopathy attributable to Still's disease, CRP level within normal limits, physician's global assessment of disease activity score below 10 mm on a 100 mm VAS, and a documented morning stiffness ≤15 min.

  41. Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y Proxy (4-7 years).

    Time frame: Week 4 to Week 54

    To evaluate the health status in anakinra treated patients with Still's disease.

  42. Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y (8-15 years).

    Time frame: Week 4 to Week 54

    To evaluate the health status in anakinra treated patients with Still's disease.

  43. Change in the number/proportion of patients reporting problems by dimension of EQ-5D-3L(≥ 16 years).

    Time frame: Week 4 to Week 54

    To evaluate the health status in anakinra treated patients with Still's disease.

  44. ACR30 response with absence of fever during the 7 days preceding the study visits over time.

    Time frame: Week 2 to Week 54

    To evaluate sustained efficacy of anakinra in patients responding to study drug.

  45. To evaluate the occurrence of study drug discontinuation in anakinra treated patients with Still's disease.

    Time frame: Day 1 to Week 54

    • Time to study drug discontinuation due to lack of efficacy or progressive disease.
    • Time to study drug discontinuation due to any reason.
    • Number of patients discontinuing study treatment.

  46. Time of initiation of glucocorticoids tapering.

    Time frame: Week 2 to Week 54

    To evaluate glucocorticoids tapering in anakinra treated patients with Still's disease.

  47. Percentage decrease of glucocorticoids dose for patients tapering their glucocorticoids dose.

    Time frame: Week 2 to Week 54

    To evaluate glucocorticoids tapering in anakinra treated patients with Still's disease.

  48. Discontinuation of glucocorticoids.

    Time frame: Week 2 to Week 54

    To evaluate glucocorticoids tapering in anakinra treated patients with Still's disease.

  49. - Occurrence of adverse events (AEs) (serious adverse events [SAEs] and non-SAEs).

    Time frame: Baseline to Week 58

    To evaluate the safety of anakinra in patients with Still ́s disease.

  50. Occurrence of deaths

    Time frame: Baseline to Week 58

    To evaluate the safety of anakinra in patients with Still ́s disease.

  51. Occurrence of AEs leading to study drug discontinuation at all study visits.

    Time frame: Baseline to Week 58

    To evaluate the safety of anakinra in patients with Still ́s disease.

  52. Occurrence of vital signs changes from baseline, including blood pressure, heart rate, and body weight at all study visits up to Week 58 visit. Changes of height in patients younger than 19 years old.

    Time frame: Baseline to Week 58

    To evaluate the safety of anakinra in patients with Still ́s disease.

  53. Occurrence of laboratory safety assessments changes over time.

    Time frame: Baseline to Week 58

    To evaluate the safety of anakinra in patients with Still ́s disease.

  54. Occurrence of abnormal laboratory values.

    Time frame: Baseline to Week 58

    To evaluate the safety of anakinra in patients with Still ́s disease.

  55. To evaluate immunogenicity of anakinra in patients with Still's disease.

    Time frame: Baseline, Weeks 2, 4, 12, 34, 54 and 58

    • Occurrence of ADAs, NAbs, cross-reactivity, and titer levels of ADAs and NAbs
    • Occurrence and titer levels of ADAs in relation to AEs
    • Occurrence and titer levels of ADAs, NAbs cross-reactivityin relation to ACR30 response and CRP levels

  56. To evaluate the pharmacokinetic of anakinra in patients with Still's disease

    Time frame: Baseline, Weeks 1 and 2

    Anakinra serum concentrations

Sponsors and collaborators

Lead sponsor

Swedish Orphan Biovitrum

Industry

Collaborators

  • CMIC Co, Ltd. Japan

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2025
Study completion
2026
First posted
Apr 14, 2023
Registry last updated
Mar 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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