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TerminatedNCT03265132anaSTILLsUpdated Jun 30, 2021Results posted

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

A Phase 3 interventional study of anakinra and Placebo in Still's Disease, Adult-Onset and Still's Disease, Juvenile-Onset, sponsored by Swedish Orphan Biovitrum. Terminated at 39 sites in 2 countries. Per ClinicalTrials.gov, last updated 2021-06-30.

Sponsored by Swedish Orphan Biovitrum · Phase 3, Interventional, and Treatment

Why this study was terminated
Meeting enrolment target (81 pat) will not be feasible within reasonable time.
Phase
Phase 3
Study type
Interventional
Enrollment
13
Allocation
Randomized
Sex
All
01

Study summary

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).

Read the detailed description

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.

02

Conditions studied

  • Still's Disease, Adult-Onset
  • Still's Disease, Juvenile-Onset

Keywords

  • Interleukin 1 receptor antagonist
  • IL-1 receptor antagonist
  • Kineret
  • anakinra
  • Adult-Onset Still's Disease
  • Systemic Juvenile Idiopathic Arthritis
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
13 participants (actual)

Study arms

  • Experimental
    anakinra

    2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day)

    Biological: anakinra

  • Placebo comparator
    Placebo

    Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day

    Drug: Placebo

Interventions

  • Biologicalanakinra

    sub cutaneous injection

    Also known as: Kineret

  • DrugPlacebo

    sub cutaneous injection

05

What researchers measure

Primary outcomes

  1. Proportion of ACR30 Responders With Absence of Fever Attributable to the Disease During the 7 Days Preceding Week 2.

    ACR30 response is defined as an improvement of ≥ 30% from baseline in at least 3 of any 6 variables listed below. Also no more than 1 of the 6 variables may worsen by \>30% from baseline. (ACR: American College of Rheumatology) 1. Physician global assessment of disease activity - Assessed on a Visual Analogue Scale (VAS) from no disease activity (0 mm) to very severe disease activity (100 mm). 2. Patient/parent global assessment of overall well-being - Assessed on a VAS from very well (0 mm) to very poor (100 mm). 3. Number of joints with active arthritis. 4. Number of joints with limitation of motion. 5. Assessment of physical function - Patient Reported Outcome instruments : Childhood Health Assessment Questionnaire (CHAQ) /Stanford Health Assessment Questionnaire (SHAQ). 6. C-Reactive Protein (CRP) (mg/L).

    Time frame: Week 2

Secondary outcomes

  1. Proportion of ACR30 Responders With Absence of Fever During 24 Hours Preceding Week 1.

    ACR30 response is defined as an improvement of ≥ 30% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

    Time frame: Week 1

  2. Proportion of ACR50 Responders With Absence of Fever During 24 Hours Preceding Week 1.

    ACR50 response is defined as an improvement of ≥ 50% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

    Time frame: Week 1

  3. Proportion of ACR70 Responders With Absence of Fever During 24 Hours Preceding Week 1.

    ACR70 response is defined as an improvement of ≥ 70% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

    Time frame: Week 1

  4. Proportion of ACR90 Responders With Absence of Fever During 24 Hours Preceding Week 1.

    ACR90 response is defined as an improvement of ≥ 90% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

    Time frame: Week 1

  5. Proportion of ACR50 Responders With Absence of Fever During 7 Days Preceding Week 2.

    ACR50 response is defined as an improvement of ≥ 50% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

    Time frame: Week 2

  6. Proportion of ACR70 Responders With Absence of Fever During 7 Days Preceding Week 2.

    ACR70 response is defined as an improvement of ≥ 70% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

    Time frame: Week 2

  7. Proportion of ACR90 Responders With Absence of Fever During 7 Days Preceding Week 2.

    ACR90 response is defined as an improvement of ≥ 90% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome . Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

    Time frame: Week 2

  8. Proportion of Responders in Physician Global Assessment of Disease Activity.

    Assessed on a VAS from no disease activity (0 mm) to very severe disease activity (100 mm). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.

    Time frame: Week 2

  9. Proportion of Responders in Patient/Parent Global Assessment of Overall Well-being.

    Assessed on a VAS from very well (0 mm) to very poor. (100 mm). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.

    Time frame: Week 2

  10. Proportion of Responders in Number of Joints With Active Arthritis.

    Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.

    Time frame: Week 2

  11. Proportion of Responders in Number of Joints With Limitation of Motion.

    Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.

    Time frame: Week 2

  12. Proportion of Responders in Assessment of Physical Function (CHAQ/SHAQ).

    Childhood Health Assessment Questionnaire (CHAQ) and Stanford Health Assessment Questionnaire (SHAQ) assess physical and functional status (see Clinical protocol section 6.5.4.1.5). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.

    Time frame: Week 2

  13. Proportion of Responders in CRP (mg/L).

    Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.

    Time frame: Week 2

  14. Proportion of Patients With Absence of Fever During the 7 Days Preceding Week 2.

    Proportion of patients with absence of fever during the 7 days preceding Week 2.

    Time frame: Week 2

  15. Proportion of Patients With Absence of Fever During the 24 Hours Preceding Week 1.

    Absence of fever during the 24 hours preceding week 1.

    Time frame: Week 1

  16. Change From Baseline in Physician Global Assessment of Disease Activity at Week 1.

    Change from baseline in Physician global assessment of disease activity measured on a VAS 0 (very well)-100 (very poor) at Week 1.

    Time frame: Day 1 and Week 1

  17. Change From Baseline in Patient/Parent Global Assessment of Overall Well-being at Week 1.

    Change from baseline in patient/parent global assessment of overall well-being measured on a VAS 0 (very well)-100 (very poor) at Week 1.

    Time frame: Day 1 and Week 1

  18. Change From Baseline in CRP.

    Change from baseline in C-Reactive Protein (CRP). CRP is measured in mg/L.

    Time frame: Day 1 and Week 1

  19. Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response.

    Proportion of patients that still meet the corresponding week 2 response with absence of fever in the preceding 7 days. Only the strictest criteria, ACR90, is reported here.

    Time frame: Week 12

  20. Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response in Relation to Glucocorticoid Tapering.

    Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available.

    Time frame: Week 2, Week 4, Week 8 and Week 12

  21. Proportion of Patients With Absence of Rash.

    Absence of rash is evaluated 24 hours preceding Week 1 and 7 days preceding Week 2, Week 4, Week 8 and Week 12. Only data at Week 2 reported here.

    Time frame: Week 2

  22. Change From Baseline in CRP.

    Change from baseline in CRP. Results at Week 2 reported here.

    Time frame: Week 2

  23. Change From Baseline in Hemoglobin (Hb). Results at Week 2 Reported Here.

    Change from baseline in Hemoglobin (Hb). Results at Week 2 reported here.

    Time frame: Week 2

  24. Change From Baseline in Platelet Count.

    Change from baseline in platelet count. Results at Week 2 reported here.

    Time frame: Week 2

  25. Change From Baseline in Ferritin.

    Change from baseline in ferritin. Results at Week 2 reported here.

    Time frame: Week 2

  26. Change From Baseline in Patient/Parent Global Assessment of Disease Related Pain.

    Assessed on a VAS from no pain (0 mm) to very severe pain (100 mm).

    Time frame: Week 2

  27. Time to Study Drug Discontinuation for Any Reason.

    Time to study drug discontinuation was analyzed using Kaplan-Meier curves. Number of patients with premature study drug discontinuation for any reason is reported here.

    Time frame: From Day 1 to Week12

  28. Time to Study Drug Discontinuation Due to Lack of Efficacy or Progressive Disease.

    Proportion of study drug discontinuation due to lack of efficacy or progressive disease was analyzed using Kaplan-Meier curves. Number of patients discontinuing study drug due to lack of efficacy or progressive disease is reported here.

    Time frame: From Day 1 to Week12

  29. Proportion of Patients Who Have Initiated Tapering of Glucocorticoids.

    Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available

    Time frame: From Week 2 to Week12

  30. Proportion of Patients That Have Decreased the Glucocorticoid Dose With at Least 50% From Baseline.

    Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available

    Time frame: From Week 2 to Week12

  31. Percentage Decrease of the Glucocorticoid Dose From Baseline.

    Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available

    Time frame: From Day 1 to Week12

  32. Proportion of Patients With at Least One Adverse Event.

    All adverse events collected from start of study treatment up to 28 days after stopping study treatment.

    Time frame: From Day 1 to Week 16

  33. Proportion of Patients With at Least One Serious Adverse Event Including Death.

    Serious adverse events (SAEs) will be collected from informed consent up to 28 days after stopping study treatment.

    Time frame: From Informed consent to Week 16

  34. Proportion of Patients With Macrophage Activation Syndrome (MAS).

    Proportion of patients with Macrophage Activation Syndrome (MAS).

    Time frame: From Day 1 to Week 16

  35. Proportion of Patients With Antidrug Antibodies (ADA) Against Anakinra.

    Proportion of patients with antidrug antibodies (ADA) against anakinra.

    Time frame: Week 2

  36. Proportion of Patients With Neutralizing Antibodies.

    Confirmed ADA positive samples will be analyzed for the presence of neutralizing antibodies.

    Time frame: Week 2

  37. Anakinra Serum Pre-dose Concentrations.

    Week 2 reported here.

    Time frame: Week 2

  38. Anakinra Serum Pharmacokinetic Parameters: Cmax,

    PK parameters only available for 2 patients.

    Time frame: Week 12

  39. Anakinra Serum Pharmacokinetic Parameters, Tmax and T½

    PK parameters only available for 2 patients

    Time frame: Week 12

  40. Anakinra Serum Pharmacokinetic Parameter: AUC 0-24 h

    PK parameters only available for 2 patients

    Time frame: Week 12

  41. Anakinra Serum Pharmacokinetic Parameter: CL/F

    Pharmacokinetic parameters only available for 2 patients

    Time frame: Week 12

  42. Anakinra Serum Pharmacokinetic Parameter: Vd/F

    PK parameters only available for 2 patients

    Time frame: Week 12

  43. Change From Baseline in JADAS27.

    Juvenile Arthritis Disease Activity Score (JADAS) includes 4 measures: physician global assessment of disease activity, patient or parent global assessment of overall well-being, 27 active joint count, and CRP. The JADAS27 includes the 27 joints. JADAS27 is calculated as the sum of its four components, physician global assessment of disease activity converted to cm from the VAS (0=no activity, 10=maximum activity); patient global assessment of well-being converted to cm from the VAS (0=very well, 10=very poor); active joint count (0-27); and CRP. Prior to calculation CRP is truncated to a 0 - 10 scale according to the following formula: (CRP (mg/l) -10)/10. Before calculation, CRP values \<10 mg/l are converted to 10 and CRP values \>110 mg/l are converted to 110. The JADAS27 tool yields a global score of 0-57. Only results from Week 2 reported here.

    Time frame: Week 2

  44. Number of Days Off School or Work Due to Still's Disease.

    Number of days off school or work due to Still's disease week 1-2.

    Time frame: Week 2

  45. Proportion of Patients With Inactive Disease.

    Inactive disease is a composite of the following parameters: no joints with active arthritis, no fever, no rash, no serositis, no splenomegaly, 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 minutes.

    Time frame: Week 12

  46. Change From Baseline in IL-6.

    Only results from Week 2 reported here.

    Time frame: Week 2

  47. Change From Baseline in IL-18.

    Only results from Week 2 reported here

    Time frame: Week 2

  48. Change From Baseline in Serum Calprotectin.

    Change from baseline in serum calprotectin. Only results from Week 2 reported here

    Time frame: Week 2

  49. Change From Baseline in Neopterin.

    Only results from Week 2 reported here

    Time frame: Week 2

06

Results

Posted Apr 28, 2020

Participant flow

Participant flow — Overall Study
MilestoneAnakinraPlacebo
Started66
Completed60
Not completed06
Withdrew: Adverse event01
Withdrew: Lack of efficacy02
Withdrew: Progressive disease02
Withdrew: Withdrawal by subject01

Outcome measures

PrimaryProportion of ACR30 Responders With Absence of Fever Attributable to the Disease During the 7 Days Preceding Week 2.

ACR30 response is defined as an improvement of ≥ 30% from baseline in at least 3 of any 6 variables listed below. Also no more than 1 of the 6 variables may worsen by \>30% from baseline. (ACR: American College of Rheumatology) 1. Physician global assessment of disease activity - Assessed on a Visual Analogue Scale (VAS) from no disease activity (0 mm) to very severe disease activity (100 mm). 2. Patient/parent global assessment of overall well-being - Assessed on a VAS from very well (0 mm) to very poor (100 mm). 3. Number of joints with active arthritis. 4. Number of joints with limitation of motion. 5. Assessment of physical function - Patient Reported Outcome instruments : Childhood Health Assessment Questionnaire (CHAQ) /Stanford Health Assessment Questionnaire (SHAQ). 6. C-Reactive Protein (CRP) (mg/L).

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of ACR30 Responders With Absence of Fever Attributable to the Disease During the 7 Days Preceding Week 2.
ParticipantsAnakinraPlacebo
Proportion of ACR30 Responders With Absence of Fever Attributable to the Disease During the 7 Days Preceding Week 2.60
Statistical analysis
  • Placebo · Fisher Exact · p = 0.0022 · Risk difference (rd): 1.0 · 95% CI 0.42 to 1.00
SecondaryProportion of ACR30 Responders With Absence of Fever During 24 Hours Preceding Week 1.

ACR30 response is defined as an improvement of ≥ 30% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

Time frame:
Week 1
Reported as:
Count of participants · Participants
Proportion of ACR30 Responders With Absence of Fever During 24 Hours Preceding Week 1.
ParticipantsAnakinraPlacebo
Proportion of ACR30 Responders With Absence of Fever During 24 Hours Preceding Week 1.53
SecondaryProportion of ACR50 Responders With Absence of Fever During 24 Hours Preceding Week 1.

ACR50 response is defined as an improvement of ≥ 50% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

Time frame:
Week 1
Reported as:
Count of participants · Participants
Proportion of ACR50 Responders With Absence of Fever During 24 Hours Preceding Week 1.
ParticipantsAnakinraPlacebo
Proportion of ACR50 Responders With Absence of Fever During 24 Hours Preceding Week 1.52
SecondaryProportion of ACR70 Responders With Absence of Fever During 24 Hours Preceding Week 1.

ACR70 response is defined as an improvement of ≥ 70% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

Time frame:
Week 1
Reported as:
Count of participants · Participants
Proportion of ACR70 Responders With Absence of Fever During 24 Hours Preceding Week 1.
ParticipantsAnakinraPlacebo
Proportion of ACR70 Responders With Absence of Fever During 24 Hours Preceding Week 1.50
SecondaryProportion of ACR90 Responders With Absence of Fever During 24 Hours Preceding Week 1.

ACR90 response is defined as an improvement of ≥ 90% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

Time frame:
Week 1
Reported as:
Count of participants · Participants
Proportion of ACR90 Responders With Absence of Fever During 24 Hours Preceding Week 1.
ParticipantsAnakinraPlacebo
Proportion of ACR90 Responders With Absence of Fever During 24 Hours Preceding Week 1.40
SecondaryProportion of ACR50 Responders With Absence of Fever During 7 Days Preceding Week 2.

ACR50 response is defined as an improvement of ≥ 50% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of ACR50 Responders With Absence of Fever During 7 Days Preceding Week 2.
ParticipantsAnakinraPlacebo
Proportion of ACR50 Responders With Absence of Fever During 7 Days Preceding Week 2.60
SecondaryProportion of ACR70 Responders With Absence of Fever During 7 Days Preceding Week 2.

ACR70 response is defined as an improvement of ≥ 70% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome. Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of ACR70 Responders With Absence of Fever During 7 Days Preceding Week 2.
ParticipantsAnakinraPlacebo
Proportion of ACR70 Responders With Absence of Fever During 7 Days Preceding Week 2.60
SecondaryProportion of ACR90 Responders With Absence of Fever During 7 Days Preceding Week 2.

ACR90 response is defined as an improvement of ≥ 90% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome . Also no more than 1 of the 6 variables may worsen by \>30% from baseline.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of ACR90 Responders With Absence of Fever During 7 Days Preceding Week 2.
ParticipantsAnakinraPlacebo
Proportion of ACR90 Responders With Absence of Fever During 7 Days Preceding Week 2.50
SecondaryProportion of Responders in Physician Global Assessment of Disease Activity.

Assessed on a VAS from no disease activity (0 mm) to very severe disease activity (100 mm). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of Responders in Physician Global Assessment of Disease Activity.
ParticipantsAnakinraPlacebo
Proportion of Responders in Physician Global Assessment of Disease Activity.40
SecondaryProportion of Responders in Patient/Parent Global Assessment of Overall Well-being.

Assessed on a VAS from very well (0 mm) to very poor. (100 mm). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of Responders in Patient/Parent Global Assessment of Overall Well-being.
ParticipantsAnakinraPlacebo
Proportion of Responders in Patient/Parent Global Assessment of Overall Well-being.40
SecondaryProportion of Responders in Number of Joints With Active Arthritis.

Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of Responders in Number of Joints With Active Arthritis.
ParticipantsAnakinraPlacebo
Proportion of Responders in Number of Joints With Active Arthritis.32
SecondaryProportion of Responders in Number of Joints With Limitation of Motion.

Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of Responders in Number of Joints With Limitation of Motion.
ParticipantsAnakinraPlacebo
Proportion of Responders in Number of Joints With Limitation of Motion.42
SecondaryProportion of Responders in Assessment of Physical Function (CHAQ/SHAQ).

Childhood Health Assessment Questionnaire (CHAQ) and Stanford Health Assessment Questionnaire (SHAQ) assess physical and functional status (see Clinical protocol section 6.5.4.1.5). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of Responders in Assessment of Physical Function (CHAQ/SHAQ).
ParticipantsAnakinraPlacebo
Proportion of Responders in Assessment of Physical Function (CHAQ/SHAQ).40
SecondaryProportion of Responders in CRP (mg/L).

Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of Responders in CRP (mg/L).
ParticipantsAnakinraPlacebo
Proportion of Responders in CRP (mg/L).50
SecondaryProportion of Patients With Absence of Fever During the 7 Days Preceding Week 2.

Proportion of patients with absence of fever during the 7 days preceding Week 2.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of Patients With Absence of Fever During the 7 Days Preceding Week 2.
ParticipantsAnakinraPlacebo
Proportion of Patients With Absence of Fever During the 7 Days Preceding Week 2.60
SecondaryProportion of Patients With Absence of Fever During the 24 Hours Preceding Week 1.

Absence of fever during the 24 hours preceding week 1.

Time frame:
Week 1
Reported as:
Count of participants · Participants
Proportion of Patients With Absence of Fever During the 24 Hours Preceding Week 1.
ParticipantsAnakinraPlacebo
Proportion of Patients With Absence of Fever During the 24 Hours Preceding Week 1.64
SecondaryChange From Baseline in Physician Global Assessment of Disease Activity at Week 1.

Change from baseline in Physician global assessment of disease activity measured on a VAS 0 (very well)-100 (very poor) at Week 1.

Time frame:
Day 1 and Week 1
Reported as:
Mean · mm
Change From Baseline in Physician Global Assessment of Disease Activity at Week 1.
mmAnakinraPlacebo
Change From Baseline in Physician Global Assessment of Disease Activity at Week 1.-46.3 ± 32.6-30.0 ± 18.5
SecondaryChange From Baseline in Patient/Parent Global Assessment of Overall Well-being at Week 1.

Change from baseline in patient/parent global assessment of overall well-being measured on a VAS 0 (very well)-100 (very poor) at Week 1.

Time frame:
Day 1 and Week 1
Reported as:
Mean · mm
Change From Baseline in Patient/Parent Global Assessment of Overall Well-being at Week 1.
mmAnakinraPlacebo
Change From Baseline in Patient/Parent Global Assessment of Overall Well-being at Week 1.-53.7 ± 27.7-25.0 ± 31.7
SecondaryChange From Baseline in CRP.

Change from baseline in C-Reactive Protein (CRP). CRP is measured in mg/L.

Time frame:
Day 1 and Week 1
Reported as:
Mean · mg/L
Change From Baseline in CRP.
mg/LAnakinraPlacebo
Change From Baseline in CRP.-109.6 ± 63.4-22.7 ± 47.1
SecondaryProportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response.

Proportion of patients that still meet the corresponding week 2 response with absence of fever in the preceding 7 days. Only the strictest criteria, ACR90, is reported here.

Time frame:
Week 12
Reported as:
Count of participants · Participants
Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response.
ParticipantsAnakinraPlacebo
Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response.60
SecondaryProportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response in Relation to Glucocorticoid Tapering.

Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available.

Time frame:
Week 2, Week 4, Week 8 and Week 12

No measurements were reported for this outcome.

SecondaryProportion of Patients With Absence of Rash.

Absence of rash is evaluated 24 hours preceding Week 1 and 7 days preceding Week 2, Week 4, Week 8 and Week 12. Only data at Week 2 reported here.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of Patients With Absence of Rash.
ParticipantsAnakinraPlacebo
Proportion of Patients With Absence of Rash.52
SecondaryChange From Baseline in CRP.

Change from baseline in CRP. Results at Week 2 reported here.

Time frame:
Week 2
Reported as:
Mean · mg/L
Change From Baseline in CRP.
mg/LAnakinraPlacebo
Change From Baseline in CRP.-126.670 ± 66.697-33.904 ± 64.393
SecondaryChange From Baseline in Hemoglobin (Hb). Results at Week 2 Reported Here.

Change from baseline in Hemoglobin (Hb). Results at Week 2 reported here.

Time frame:
Week 2
Reported as:
Mean · g/dL
Change From Baseline in Hemoglobin (Hb). Results at Week 2 Reported Here.
g/dLAnakinraPlacebo
Change From Baseline in Hemoglobin (Hb). Results at Week 2 Reported Here.1.57 ± 0.86-0.80 ± 1.01
SecondaryChange From Baseline in Platelet Count.

Change from baseline in platelet count. Results at Week 2 reported here.

Time frame:
Week 2
Reported as:
Mean · 10^9/L
Change From Baseline in Platelet Count.
10^9/LAnakinraPlacebo
Change From Baseline in Platelet Count.-148.2 ± 52.3-26.3 ± 139.6
SecondaryChange From Baseline in Ferritin.

Change from baseline in ferritin. Results at Week 2 reported here.

Time frame:
Week 2
Reported as:
Mean · ug/L
Change From Baseline in Ferritin.
ug/LAnakinraPlacebo
Change From Baseline in Ferritin.-390.364 ± 387.521-49.383 ± 51.776
SecondaryChange From Baseline in Patient/Parent Global Assessment of Disease Related Pain.

Assessed on a VAS from no pain (0 mm) to very severe pain (100 mm).

Time frame:
Week 2
Reported as:
Mean · score on a scale
Change From Baseline in Patient/Parent Global Assessment of Disease Related Pain.
score on a scaleAnakinraPlacebo
Change From Baseline in Patient/Parent Global Assessment of Disease Related Pain.-55.6 ± 27.7-33.5 ± 28.5
SecondaryTime to Study Drug Discontinuation for Any Reason.

Time to study drug discontinuation was analyzed using Kaplan-Meier curves. Number of patients with premature study drug discontinuation for any reason is reported here.

Time frame:
From Day 1 to Week12
Reported as:
Count of participants · Participants
Time to Study Drug Discontinuation for Any Reason.
ParticipantsAnakinraPlacebo
Time to Study Drug Discontinuation for Any Reason.05
SecondaryTime to Study Drug Discontinuation Due to Lack of Efficacy or Progressive Disease.

Proportion of study drug discontinuation due to lack of efficacy or progressive disease was analyzed using Kaplan-Meier curves. Number of patients discontinuing study drug due to lack of efficacy or progressive disease is reported here.

Time frame:
From Day 1 to Week12
Reported as:
Count of participants · Participants
Time to Study Drug Discontinuation Due to Lack of Efficacy or Progressive Disease.
ParticipantsAnakinraPlacebo
Time to Study Drug Discontinuation Due to Lack of Efficacy or Progressive Disease.04
SecondaryProportion of Patients Who Have Initiated Tapering of Glucocorticoids.

Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available

Time frame:
From Week 2 to Week12

No measurements were reported for this outcome.

SecondaryProportion of Patients That Have Decreased the Glucocorticoid Dose With at Least 50% From Baseline.

Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available

Time frame:
From Week 2 to Week12

No measurements were reported for this outcome.

SecondaryPercentage Decrease of the Glucocorticoid Dose From Baseline.

Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available

Time frame:
From Day 1 to Week12

No measurements were reported for this outcome.

SecondaryProportion of Patients With at Least One Adverse Event.

All adverse events collected from start of study treatment up to 28 days after stopping study treatment.

Time frame:
From Day 1 to Week 16
Reported as:
Count of participants · Participants
Proportion of Patients With at Least One Adverse Event.
ParticipantsAnakinraPlacebo
Proportion of Patients With at Least One Adverse Event.64
SecondaryProportion of Patients With at Least One Serious Adverse Event Including Death.

Serious adverse events (SAEs) will be collected from informed consent up to 28 days after stopping study treatment.

Time frame:
From Informed consent to Week 16
Reported as:
Count of participants · Participants
Proportion of Patients With at Least One Serious Adverse Event Including Death.
ParticipantsAnakinraPlacebo
Proportion of Patients With at Least One Serious Adverse Event Including Death.01
SecondaryProportion of Patients With Macrophage Activation Syndrome (MAS).

Proportion of patients with Macrophage Activation Syndrome (MAS).

Time frame:
From Day 1 to Week 16
Reported as:
Count of participants · Participants
Proportion of Patients With Macrophage Activation Syndrome (MAS).
ParticipantsAnakinraPlacebo
Proportion of Patients With Macrophage Activation Syndrome (MAS).00
SecondaryProportion of Patients With Antidrug Antibodies (ADA) Against Anakinra.

Proportion of patients with antidrug antibodies (ADA) against anakinra.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of Patients With Antidrug Antibodies (ADA) Against Anakinra.
ParticipantsAnakinraPlacebo
Proportion of Patients With Antidrug Antibodies (ADA) Against Anakinra.61
SecondaryProportion of Patients With Neutralizing Antibodies.

Confirmed ADA positive samples will be analyzed for the presence of neutralizing antibodies.

Time frame:
Week 2
Reported as:
Count of participants · Participants
Proportion of Patients With Neutralizing Antibodies.
ParticipantsAnakinraPlacebo
Proportion of Patients With Neutralizing Antibodies.00
SecondaryAnakinra Serum Pre-dose Concentrations.

Week 2 reported here.

Time frame:
Week 2
Reported as:
Mean · ng/mL
Anakinra Serum Pre-dose Concentrations.
ng/mLAnakinraPlacebo
Anakinra Serum Pre-dose Concentrations.157 ± 134—
SecondaryAnakinra Serum Pharmacokinetic Parameters: Cmax,

PK parameters only available for 2 patients.

Time frame:
Week 12
Reported as:
Mean · ng/mL
Anakinra Serum Pharmacokinetic Parameters: Cmax,
ng/mLPlaceboAnakinra
Anakinra Serum Pharmacokinetic Parameters: Cmax,—1990.0 ± 1315.2
SecondaryAnakinra Serum Pharmacokinetic Parameters, Tmax and T½

PK parameters only available for 2 patients

Time frame:
Week 12
Reported as:
Mean · hours
Anakinra Serum Pharmacokinetic Parameters, Tmax and T½
hoursPlaceboAnakinra
Tmax—3.06 ± 1.33
T½—5.23 ± 1.01
SecondaryAnakinra Serum Pharmacokinetic Parameter: AUC 0-24 h

PK parameters only available for 2 patients

Time frame:
Week 12
Reported as:
Mean · h*ng/mL
Anakinra Serum Pharmacokinetic Parameter: AUC 0-24 h
h*ng/mLPlaceboAnakinra
Anakinra Serum Pharmacokinetic Parameter: AUC 0-24 h—18483.3 ± 15708.4
SecondaryAnakinra Serum Pharmacokinetic Parameter: CL/F

Pharmacokinetic parameters only available for 2 patients

Time frame:
Week 12
Reported as:
Mean · mL/h*kg
Anakinra Serum Pharmacokinetic Parameter: CL/F
mL/h*kgPlaceboAnakinra
Anakinra Serum Pharmacokinetic Parameter: CL/F—170.80 ± 45.69
SecondaryAnakinra Serum Pharmacokinetic Parameter: Vd/F

PK parameters only available for 2 patients

Time frame:
Week 12
Reported as:
Mean · mL/kg
Anakinra Serum Pharmacokinetic Parameter: Vd/F
mL/kgPlaceboAnakinra
Anakinra Serum Pharmacokinetic Parameter: Vd/F—1254.52 ± 95.57
SecondaryChange From Baseline in JADAS27.

Juvenile Arthritis Disease Activity Score (JADAS) includes 4 measures: physician global assessment of disease activity, patient or parent global assessment of overall well-being, 27 active joint count, and CRP. The JADAS27 includes the 27 joints. JADAS27 is calculated as the sum of its four components, physician global assessment of disease activity converted to cm from the VAS (0=no activity, 10=maximum activity); patient global assessment of well-being converted to cm from the VAS (0=very well, 10=very poor); active joint count (0-27); and CRP. Prior to calculation CRP is truncated to a 0 - 10 scale according to the following formula: (CRP (mg/l) -10)/10. Before calculation, CRP values \<10 mg/l are converted to 10 and CRP values \>110 mg/l are converted to 110. The JADAS27 tool yields a global score of 0-57. Only results from Week 2 reported here.

Time frame:
Week 2
Reported as:
Mean · score on a scale
Change From Baseline in JADAS27.
score on a scaleAnakinraPlacebo
Change From Baseline in JADAS27.-21.42 ± 3.93-15.81 ± 4.83
SecondaryNumber of Days Off School or Work Due to Still's Disease.

Number of days off school or work due to Still's disease week 1-2.

Time frame:
Week 2
Reported as:
Mean · Days
Number of Days Off School or Work Due to Still's Disease.
DaysAnakinraPlacebo
Number of Days Off School or Work Due to Still's Disease.0.7 ± 1.61.3 ± 2.5
SecondaryProportion of Patients With Inactive Disease.

Inactive disease is a composite of the following parameters: no joints with active arthritis, no fever, no rash, no serositis, no splenomegaly, 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 minutes.

Time frame:
Week 12
Reported as:
Count of participants · Participants
Proportion of Patients With Inactive Disease.
ParticipantsAnakinraPlacebo
Proportion of Patients With Inactive Disease.30
SecondaryChange From Baseline in IL-6.

Only results from Week 2 reported here.

Time frame:
Week 2
Reported as:
Mean · ng/L
Change From Baseline in IL-6.
ng/LAnakinraPlacebo
Change From Baseline in IL-6.-30.048 ± 23.262-24.818 ± 25.940
SecondaryChange From Baseline in IL-18.

Only results from Week 2 reported here

Time frame:
Week 2
Reported as:
Mean · ng/L
Change From Baseline in IL-18.
ng/LAnakinraPlacebo
Change From Baseline in IL-18.-7968.0 ± 7564.4-20701.7 ± 32766.4
SecondaryChange From Baseline in Serum Calprotectin.

Change from baseline in serum calprotectin. Only results from Week 2 reported here

Time frame:
Week 2
Reported as:
Mean · mg/L
Change From Baseline in Serum Calprotectin.
mg/LAnakinraPlacebo
Change From Baseline in Serum Calprotectin.-100.038 ± 113.349-26.021 ± 23.819
SecondaryChange From Baseline in Neopterin.

Only results from Week 2 reported here

Time frame:
Week 2
Reported as:
Mean · nmol/L
Change From Baseline in Neopterin.
nmol/LAnakinraPlacebo
Change From Baseline in Neopterin.-3.08 ± 5.69-8.00 ± 10.82

Adverse events

Collected over From the start of study treatment up to 28 days after stopping study treatment.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Anakinra0/6 (0%)0/6 (0%)6/6 (100%)
Placebo0/6 (0%)1/6 (16.7%)4/6 (66.7%)
Most frequent serious events
Most frequent serious events
EventAnakinraPlacebo
Diffuse large B-cell lymphoma stage IIINeoplasms benign, malignant and unspecified (incl cysts and polyps)0/61/6
Most frequent other events
Showing 10 of 28
Most frequent other events
EventAnakinraPlacebo
Upper respiratory infectionInfections and infestations3/60/6
RhinorrhoeaRespiratory, thoracic and mediastinal disorders2/60/6
VomitingGastrointestinal disorders2/60/6
Injection site reactionGeneral disorders2/61/6
Ear infectionInfections and infestations1/60/6
Urinary tract infectionInfections and infestations0/61/6
Viral upper respiratory tract infectionInfections and infestations1/60/6
AnxietyPsychiatric disorders1/60/6
DepressionPsychiatric disorders0/61/6
DizzinessNervous system disorders1/61/6

Baseline characteristics

Age, Continuous
Age, Continuous(years)PlaceboAnakinraTotal
Mean14.4 ± 13.212.3 ± 19.313.3 ± 16.0
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboAnakinraTotal
Female325
Male246
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PlaceboAnakinraTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American112
White459
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)PlaceboAnakinraTotal
United States5611
Still's disease symptom duration
Still's disease symptom duration(Days)PlaceboAnakinraTotal
Mean32.4 ± 18.7109.0 ± 78.074.2 ± 69.1
07

Study locations

39 sites
  • University of Alabama Birmingham
    Birmingham, Alabama 35294, United States
  • Attune Health
    Beverly Hills, California 90211, United States
  • Rady Children's Hospital & Health Center
    San Diego, California 92123, United States
  • The Children's Hospital Colorado
    Aurora, Colorado 80045, United States
  • University of Florida
    Gainesville, Florida 32611, United States
  • University of Miami
    Miami, Florida 33124, United States
  • Nicklaus Children's Hospital
    Miami, Florida 33155, United States
  • University of Iowa Hospitals and Clinics
    Iowa City, Iowa 52242, United States
  • Children's Mercy Hospital and Clinics
    Kansas City, Kansas 67208, United States
  • University of Louisville School of Medicine Research Foundation
    Louisville, Kentucky 40202, United States
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02115, United States
  • Boston Children's Hospital
    Boston, Massachusetts 02115, United States
  • University of Michigan
    Ann Arbor, Michigan 48109, United States
  • Saint Paul Rheumatology
    Eagan, Minnesota 55121, United States
  • University of Minnesota
    Minneapolis, Minnesota 55454, United States
  • Saint Louis University
    Saint Louis, Missouri 63104, United States
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • Institute for Rheumatic and Autoimmune Diseases
    Summit, New Jersey 07901, United States
  • Hospital for Special Surgery
    New York, New York 10021, United States
  • Columbia University Medical Center
    New York, New York 10032, United States
  • UNC Hospitals
    Chapel Hill, North Carolina 27514, United States
  • Duke Children's Hospital and Health Center
    Durham, North Carolina 27710, United States
  • Wake Forest Baptist Brenner Medical Center
    Winston-Salem, North Carolina 27157, United States
  • MetroHealth System
    Cleveland, Ohio 44109, United States
  • Nationwide Children's Hospital
    Columbus, Ohio 43205, United States
  • Children's Hospital of Pittsburgh of UPMC
    Pittsburgh, Pennsylvania 15224, United States
  • Monroe Carell Jr. Children's Hospital at Vanderbilt
    Nashville, Tennessee 37232, United States
  • Baylor Research Institute
    Dallas, Texas 75204, United States
  • Univ of TX Southwestern Medical Center Dallas - Texas Scottish Rite Hospital for Children
    Dallas, Texas 75219, United States
  • Texas Children's Hospital
    Houston, Texas 77030, United States
  • University of Texas Health Science Center at San Antonio
    San Antonio, Texas 78229, United States
  • University of Utah Hospitals and Clinics
    Salt Lake City, Utah 84113, United States
  • University of Vermont Medical Center
    Burlington, Vermont 05401, United States
  • Virginia Commonwealth University
    Richmond, Virginia 23298, United States
  • University of Washington
    Seattle, Washington 98195, United States
  • Medical College of Wisconsin
    Milwaukee, Wisconsin 53226, United States
  • University of Calgary - Alberta Children's Hospital
    Calgary, Canada
  • University of Calgary
    Calgary, Canada
  • The Hospital for Sick Children
    Toronto, Canada
08

References and documents

Study documents

  • Study protocol · Jul 3, 2018
  • Statistical analysis plan · Jul 24, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03265132
Lead sponsor
Swedish Orphan Biovitrum
Responsible party
Sponsor
First posted
Aug 29, 2017
Start date
Sep 26, 2017
Primary completion
Feb 13, 2019
Completion
May 23, 2019
Results posted
Apr 28, 2020
Last update
Jun 30, 2021

Study contacts

Sven Ohlman, MD PhD
study director · Swedish Orphan Biovitrum

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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