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

• Sponsor: Swedish Orphan Biovitrum (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03265132
• Collaborator: (none)
• Enrollment: 13
• Locations: 39
• Arms: 2
• Actual Duration (Months): 19.8
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Still's Disease, Adult-Onset; Still's Disease, Juvenile-Onset	Biological: anakinra; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Sep 26, 2017
• Actual Primary Completion Date: Feb 13, 2019
• Actual Study Completion Date: May 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: anakinra 2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day)	Biological: anakinra; sub cutaneous injection; Other Names: Kineret
Placebo Comparator: Placebo Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day	Drug: Placebo; sub cutaneous injection

Outcome Measures

Primary Outcome Measures

1. Proportion of ACR30 Responders With Absence of Fever Attributable to the Disease During the 7 Days Preceding Week 2. [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) 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). Patient/parent global assessment of overall well-being - Assessed on a VAS from very well (0 mm) to very poor (100 mm). Number of joints with active arthritis. Number of joints with limitation of motion. Assessment of physical function - Patient Reported Outcome instruments : Childhood Health Assessment Questionnaire (CHAQ) /Stanford Health Assessment Questionnaire (SHAQ). C-Reactive Protein (CRP) (mg/L).

Secondary Outcome Measures

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

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

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

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

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

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

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

8. Proportion of Responders in Physician Global Assessment of Disease Activity. [Week 2]

   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.

9. Proportion of Responders in Patient/Parent Global Assessment of Overall Well-being. [Week 2]

   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.

10. Proportion of Responders in Number of Joints With Active Arthritis. [Week 2]

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

11. Proportion of Responders in Number of Joints With Limitation of Motion. [Week 2]

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

12. Proportion of Responders in Assessment of Physical Function (CHAQ/SHAQ). [Week 2]

    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.

13. Proportion of Responders in CRP (mg/L). [Week 2]

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

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

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

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

    Absence of fever during the 24 hours preceding week 1.

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

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

18. Change From Baseline in CRP. [Day 1 and Week 1]

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

19. Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response. [Week 12]

    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.

20. Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response in Relation to Glucocorticoid Tapering. [Week 2, Week 4, Week 8 and Week 12]

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

21. Proportion of Patients With Absence of Rash. [Week 2]

    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.

22. Change From Baseline in CRP. [Week 2]

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

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

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

24. Change From Baseline in Platelet Count. [Week 2]

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

25. Change From Baseline in Ferritin. [Week 2]

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

26. Change From Baseline in Patient/Parent Global Assessment of Disease Related Pain. [Week 2]

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

27. Time to Study Drug Discontinuation for Any Reason. [From Day 1 to Week12]

    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.

28. Time to Study Drug Discontinuation Due to Lack of Efficacy or Progressive Disease. [From Day 1 to Week12]

    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.

29. Proportion of Patients Who Have Initiated Tapering of Glucocorticoids. [From Week 2 to Week12]

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

30. Proportion of Patients That Have Decreased the Glucocorticoid Dose With at Least 50% From Baseline. [From Week 2 to Week12]

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

31. Percentage Decrease of the Glucocorticoid Dose From Baseline. [From Day 1 to Week12]

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

32. Proportion of Patients With at Least One Adverse Event. [From Day 1 to Week 16]

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

33. Proportion of Patients With at Least One Serious Adverse Event Including Death. [From Informed consent to Week 16]

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

34. Proportion of Patients With Macrophage Activation Syndrome (MAS). [From Day 1 to Week 16]

    Proportion of patients with Macrophage Activation Syndrome (MAS).

35. Proportion of Patients With Antidrug Antibodies (ADA) Against Anakinra. [Week 2]

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

36. Proportion of Patients With Neutralizing Antibodies. [Week 2]

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

37. Anakinra Serum Pre-dose Concentrations. [Week 2]

    Week 2 reported here.

38. Anakinra Serum Pharmacokinetic Parameters: Cmax, [Week 12]

    PK parameters only available for 2 patients.

39. Anakinra Serum Pharmacokinetic Parameters, Tmax and T½ [Week 12]

    PK parameters only available for 2 patients

40. Anakinra Serum Pharmacokinetic Parameter: AUC 0-24 h [Week 12]

    PK parameters only available for 2 patients

41. Anakinra Serum Pharmacokinetic Parameter: CL/F [Week 12]

    Pharmacokinetic parameters only available for 2 patients

42. Anakinra Serum Pharmacokinetic Parameter: Vd/F [Week 12]

    PK parameters only available for 2 patients

43. Change From Baseline in JADAS27. [Week 2]

    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.

44. Number of Days Off School or Work Due to Still's Disease. [Week 2]

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

45. Proportion of Patients With Inactive Disease. [Week 12]

    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.

46. Change From Baseline in IL-6. [Week 2]

    Only results from Week 2 reported here.

47. Change From Baseline in IL-18. [Week 2]

    Only results from Week 2 reported here

48. Change From Baseline in Serum Calprotectin. [Week 2]

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

49. Change From Baseline in Neopterin. [Week 2]

    Only results from Week 2 reported here

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: 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:

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.

1. Live vaccines within 1 month prior to randomization.

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

3. Clinical evidence of liver disease or liver injury.

4. Presence of severe renal function impairment.

5. Presence of neutropenia.

6. Presence or suspicion of MAS at baseline.

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

8. History of malignancy within 5 years.

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

10. Pregnant or lactating women.

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

12. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Birmingham	Birmingham	Alabama	United States	35294
2	Attune Health	Beverly Hills	California	United States	90211
3	Rady Children's Hospital & Health Center	San Diego	California	United States	92123
4	The Children's Hospital Colorado	Aurora	Colorado	United States	80045
5	University of Florida	Gainesville	Florida	United States	32611
6	University of Miami	Miami	Florida	United States	33124
7	Nicklaus Children's Hospital	Miami	Florida	United States	33155
8	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
9	Children's Mercy Hospital and Clinics	Kansas City	Kansas	United States	67208
10	University of Louisville School of Medicine Research Foundation	Louisville	Kentucky	United States	40202
11	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
12	Boston Children's Hospital	Boston	Massachusetts	United States	02115
13	University of Michigan	Ann Arbor	Michigan	United States	48109
14	Saint Paul Rheumatology	Eagan	Minnesota	United States	55121
15	University of Minnesota	Minneapolis	Minnesota	United States	55454
16	Saint Louis University	Saint Louis	Missouri	United States	63104
17	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
18	Institute for Rheumatic and Autoimmune Diseases	Summit	New Jersey	United States	07901
19	Hospital for Special Surgery	New York	New York	United States	10021
20	Columbia University Medical Center	New York	New York	United States	10032
21	UNC Hospitals	Chapel Hill	North Carolina	United States	27514
22	Duke Children's Hospital and Health Center	Durham	North Carolina	United States	27710
23	Wake Forest Baptist Brenner Medical Center	Winston-Salem	North Carolina	United States	27157
24	MetroHealth System	Cleveland	Ohio	United States	44109
25	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
26	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
27	Monroe Carell Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee	United States	37232
28	Baylor Research Institute	Dallas	Texas	United States	75204
29	Univ of TX Southwestern Medical Center Dallas - Texas Scottish Rite Hospital for Children	Dallas	Texas	United States	75219
30	Texas Children's Hospital	Houston	Texas	United States	77030
31	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
32	University of Utah Hospitals and Clinics	Salt Lake City	Utah	United States	84113
33	University of Vermont Medical Center	Burlington	Vermont	United States	05401
34	Virginia Commonwealth University	Richmond	Virginia	United States	23298
35	University of Washington	Seattle	Washington	United States	98195
36	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
37	University of Calgary - Alberta Children's Hospital	Calgary		Canada
38	University of Calgary	Calgary		Canada
39	The Hospital for Sick Children	Toronto		Canada

Sponsors and Collaborators

• Swedish Orphan Biovitrum

Investigators

• Study Director: Sven Ohlman, MD PhD, Swedish Orphan Biovitrum

Study Documents (Full-Text)

• Study Protocol - Jul 3, 2018
• Statistical Analysis Plan - Jul 24, 2019

More Information

Publications

None provided.

• Responsible Party: Swedish Orphan Biovitrum
• ClinicalTrials.gov Identifier: NCT03265132
• Other Study ID Numbers: Sobi.ANAKIN-301
• First Posted: Aug 29, 2017
• Last Update Posted: Jun 30, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Swedish Orphan Biovitrum: Interleukin 1 receptor antagonist; IL-1 receptor antagonist; Kineret; anakinra; Adult-Onset Still's Disease; Systemic Juvenile Idiopathic Arthritis
• Additional relevant MeSH terms: Arthritis, Juvenile; Still's Disease, Adult-Onset; Interleukin 1 Receptor Antagonist Protein

Study Results

Participant Flow

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Period Title: Overall Study
STARTED	6	6
COMPLETED	6	0
NOT COMPLETED	0	6

Baseline Characteristics

Arm/Group Title	Placebo	Anakinra	Total
Arm/Group Description	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Total of all reporting groups
Overall Participants	5	6	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.4 (13.2)	12.3 (19.3)	13.3 (16.0)
Sex: Female, Male (Count of Participants)
Female	3 60%	2 33.3%	5 45.5%
Male	2 40%	4 66.7%	6 54.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 20%	1 16.7%	2 18.2%
White	4 80%	5 83.3%	9 81.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	6 100%	11 100%
Still's disease symptom duration (Days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days]	32.4 (18.7)	109.0 (78.0)	74.2 (69.1)

Outcome Measures

1. Primary Outcome

Title	Proportion of ACR30 Responders With Absence of Fever Attributable to the Disease During the 7 Days Preceding Week 2.
Description	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) 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). Patient/parent global assessment of overall well-being - Assessed on a VAS from very well (0 mm) to very poor (100 mm). Number of joints with active arthritis. Number of joints with limitation of motion. Assessment of physical function - Patient Reported Outcome instruments : Childhood Health Assessment Questionnaire (CHAQ) /Stanford Health Assessment Questionnaire (SHAQ). C-Reactive Protein (CRP) (mg/L).
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	6 120%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0022
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; 0.42 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	5 100%	3 50%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	5 100%	2 33.3%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	5 100%	0 0%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	4 80%	0 0%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	6 120%	0 0%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	6 120%	0 0%

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	5 100%	0 0%

9. Secondary Outcome

Title	Proportion of Responders in Physician Global Assessment of Disease Activity.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	4 80%	0 0%

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	4
Count of Participants [Participants]	4 80%	0 0%

11. Secondary Outcome

Title	Proportion of Responders in Number of Joints With Active Arthritis.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	3 60%	2 33.3%

12. Secondary Outcome

Title	Proportion of Responders in Number of Joints With Limitation of Motion.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	4 80%	2 33.3%

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	4 80%	0 0%

14. Secondary Outcome

Title	Proportion of Responders in CRP (mg/L).
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	5 100%	0 0%

15. Secondary Outcome

Title	Proportion of Patients With Absence of Fever During the 7 Days Preceding Week 2.
Description	Proportion of patients with absence of fever during the 7 days preceding Week 2.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	6 120%	0 0%

16. Secondary Outcome

Title	Proportion of Patients With Absence of Fever During the 24 Hours Preceding Week 1.
Description	Absence of fever during the 24 hours preceding week 1.
Time Frame	Week 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	6 120%	4 66.7%

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Mean (Standard Deviation) [mm]	-46.3 (32.6)	-30.0 (18.5)

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	4
Mean (Standard Deviation) [mm]	-53.7 (27.7)	-25.0 (31.7)

19. Secondary Outcome

Title	Change From Baseline in CRP.
Description	Change from baseline in C-Reactive Protein (CRP). CRP is measured in mg/L.
Time Frame	Day 1 and Week 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Mean (Standard Deviation) [mg/L]	-109.6 (63.4)	-22.7 (47.1)

20. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	6 120%	0 0%

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

No patients were treated with any systemic glucocorticoids at randomization

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	0	0

22. Secondary Outcome

Title	Proportion of Patients With Absence of Rash.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	4
Count of Participants [Participants]	5 100%	2 33.3%

23. Secondary Outcome

Title	Change From Baseline in CRP.
Description	Change from baseline in CRP. Results at Week 2 reported here.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Mean (Standard Deviation) [mg/L]	-126.670 (66.697)	-33.904 (64.393)

24. Secondary Outcome

Title	Change From Baseline in Hemoglobin (Hb). Results at Week 2 Reported Here.
Description	Change from baseline in Hemoglobin (Hb). Results at Week 2 reported here.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	3
Mean (Standard Deviation) [g/dL]	1.57 (0.86)	-0.80 (1.01)

25. Secondary Outcome

Title	Change From Baseline in Platelet Count.
Description	Change from baseline in platelet count. Results at Week 2 reported here.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	3
Mean (Standard Deviation) [10^9/L]	-148.2 (52.3)	-26.3 (139.6)

26. Secondary Outcome

Title	Change From Baseline in Ferritin.
Description	Change from baseline in ferritin. Results at Week 2 reported here.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	5	3
Mean (Standard Deviation) [ug/L]	-390.364 (387.521)	-49.383 (51.776)

27. Secondary Outcome

Title	Change From Baseline in Patient/Parent Global Assessment of Disease Related Pain.
Description	Assessed on a VAS from no pain (0 mm) to very severe pain (100 mm).
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

Patients with baseline and week 2 data analyzed.

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	4
Mean (Standard Deviation) [score on a scale]	-55.6 (27.7)	-33.5 (28.5)

28. Secondary Outcome

Title	Time to Study Drug Discontinuation for Any Reason.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	0 0%	5 83.3%

29. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	0 0%	4 66.7%

30. Secondary Outcome

Title	Proportion of Patients Who Have Initiated Tapering of Glucocorticoids.
Description	Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available
Time Frame	From Week 2 to Week12

Outcome Measure Data

Analysis Population Description

No patients were treated with any systemic glucocorticoids at randomization

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	0	0

31. Secondary Outcome

Title	Proportion of Patients That Have Decreased the Glucocorticoid Dose With at Least 50% From Baseline.
Description	Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available
Time Frame	From Week 2 to Week12

Outcome Measure Data

Analysis Population Description

No patients were treated with any systemic glucocorticoids at randomization

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	0	0

32. Secondary Outcome

Title	Percentage Decrease of the Glucocorticoid Dose From Baseline.
Description	Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available
Time Frame	From Day 1 to Week12

Outcome Measure Data

Analysis Population Description

No patients were treated with any systemic glucocorticoids at randomization

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	0	0

33. Secondary Outcome

Title	Proportion of Patients With at Least One Adverse Event.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	6
Count of Participants [Participants]	6 120%	4 66.7%

34. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	6
Count of Participants [Participants]	0 0%	1 16.7%

35. Secondary Outcome

Title	Proportion of Patients With Macrophage Activation Syndrome (MAS).
Description	Proportion of patients with Macrophage Activation Syndrome (MAS).
Time Frame	From Day 1 to Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	6
Count of Participants [Participants]	0 0%	0 0%

36. Secondary Outcome

Title	Proportion of Patients With Antidrug Antibodies (ADA) Against Anakinra.
Description	Proportion of patients with antidrug antibodies (ADA) against anakinra.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	6
Count of Participants [Participants]	6 120%	1 16.7%

37. Secondary Outcome

Title	Proportion of Patients With Neutralizing Antibodies.
Description	Confirmed ADA positive samples will be analyzed for the presence of neutralizing antibodies.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	6
Count of Participants [Participants]	0 0%	0 0%

38. Secondary Outcome

Title	Anakinra Serum Pre-dose Concentrations.
Description	Week 2 reported here.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

No data available for the placebo group as they did not receive anakinra.

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	4	0
Mean (Standard Deviation) [ng/mL]	157 (134)

39. Secondary Outcome

Title	Anakinra Serum Pharmacokinetic Parameters: Cmax,
Description	PK parameters only available for 2 patients.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

PK parameters only available for 2 anakinra treated patients.

Arm/Group Title	Placebo	Anakinra
Arm/Group Description	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection
Measure Participants	0	2
Mean (Standard Deviation) [ng/mL]	1990.0 (1315.2)

40. Secondary Outcome

Title	Anakinra Serum Pharmacokinetic Parameters, Tmax and T½
Description	PK parameters only available for 2 patients
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

PK parameters only available for 2 patients

Arm/Group Title	Placebo	Anakinra
Arm/Group Description	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection
Measure Participants	0	2
Tmax	3.06 (1.33)
T½	5.23 (1.01)

41. Secondary Outcome

Title	Anakinra Serum Pharmacokinetic Parameter: AUC 0-24 h
Description	PK parameters only available for 2 patients
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

PK parameters only available for 2 anakinra treated patients

Arm/Group Title	Placebo	Anakinra
Arm/Group Description	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection
Measure Participants	0	2
Mean (Standard Deviation) [h*ng/mL]	18483.3 (15708.4)

42. Secondary Outcome

Title	Anakinra Serum Pharmacokinetic Parameter: CL/F
Description	Pharmacokinetic parameters only available for 2 patients
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters only available for 2 anakinra treated patients

Arm/Group Title	Placebo	Anakinra
Arm/Group Description	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection
Measure Participants	0	2
Mean (Standard Deviation) [mL/h*kg]	170.80 (45.69)

43. Secondary Outcome

Title	Anakinra Serum Pharmacokinetic Parameter: Vd/F
Description	PK parameters only available for 2 patients
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

PK parameters only available for 2 anakinra treated patients

Arm/Group Title	Placebo	Anakinra
Arm/Group Description	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection
Measure Participants	0	2
Mean (Standard Deviation) [mL/kg]	1254.52 (95.57)

44. Secondary Outcome

Title	Change From Baseline in JADAS27.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	4
Mean (Standard Deviation) [score on a scale]	-21.42 (3.93)	-15.81 (4.83)

45. Secondary Outcome

Title	Number of Days Off School or Work Due to Still's Disease.
Description	Number of days off school or work due to Still's disease week 1-2.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	4
Mean (Standard Deviation) [Days]	0.7 (1.6)	1.3 (2.5)

46. Secondary Outcome

Title	Proportion of Patients With Inactive Disease.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	5
Count of Participants [Participants]	3 60%	0 0%

47. Secondary Outcome

Title	Change From Baseline in IL-6.
Description	Only results from Week 2 reported here.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	3
Mean (Standard Deviation) [ng/L]	-30.048 (23.262)	-24.818 (25.940)

48. Secondary Outcome

Title	Change From Baseline in IL-18.
Description	Only results from Week 2 reported here
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	5	3
Mean (Standard Deviation) [ng/L]	-7968.0 (7564.4)	-20701.7 (32766.4)

49. Secondary Outcome

Title	Change From Baseline in Serum Calprotectin.
Description	Change from baseline in serum calprotectin. Only results from Week 2 reported here
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	6	3
Mean (Standard Deviation) [mg/L]	-100.038 (113.349)	-26.021 (23.819)

50. Secondary Outcome

Title	Change From Baseline in Neopterin.
Description	Only results from Week 2 reported here
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection	Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
Measure Participants	5	3
Mean (Standard Deviation) [nmol/L]	-3.08 (5.69)	-8.00 (10.82)

Adverse Events

Time Frame	From the start of study treatment up to 28 days after stopping study treatment.
Adverse Event Reporting Description	The Investigator recorded all directly observed AEs, and all AEs spontaneously reported by the patient, in the CRF. MAS was defined as an event of special interest in this study. If a MAS diagnosis was made at any point after patient signed informed consent, the event was to be reported as a serious AE and the patient should be withdrawn from the study.
Arm/Group Title	Anakinra		Placebo
Arm/Group Description	2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) anakinra: sub cutaneous injection		Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Placebo: sub cutaneous injection
All Cause Mortality
	Anakinra		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Anakinra		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		1/6 (16.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma stage III	0/6 (0%)	0	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	Anakinra		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		4/6 (66.7%)
Gastrointestinal disorders
Vomiting	2/6 (33.3%)	2	0/6 (0%)	0
Diarrhoea	1/6 (16.7%)	1	0/6 (0%)	0
Nausea	1/6 (16.7%)	1	0/6 (0%)	0
Retching	1/6 (16.7%)	1	0/6 (0%)	0
General disorders
Injection site reaction	2/6 (33.3%)	2	1/6 (16.7%)	1
Injection site erythema	1/6 (16.7%)	1	1/6 (16.7%)	1
Injection site pain	0/6 (0%)	0	1/6 (16.7%)	1
Injection site rash	1/6 (16.7%)	1	0/6 (0%)	0
Malaise	1/6 (16.7%)	1	0/6 (0%)	0
Infections and infestations
Upper respiratory infection	3/6 (50%)	3	0/6 (0%)	0
Ear infection	1/6 (16.7%)	1	0/6 (0%)	0
Urinary tract infection	0/6 (0%)	0	1/6 (16.7%)	1
Viral upper respiratory tract infection	1/6 (16.7%)	1	0/6 (0%)	0
Injury, poisoning and procedural complications
Joint injury	1/6 (16.7%)	1	0/6 (0%)	0
Thermal burn	1/6 (16.7%)	1	0/6 (0%)	0
Investigations
Vitamin D decrease	1/6 (16.7%)	1	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/6 (16.7%)	1	0/6 (0%)	0
Nervous system disorders
Dizziness	1/6 (16.7%)	1	1/6 (16.7%)	1
Headache	0/6 (0%)	0	1/6 (16.7%)	1
Neuralgia	1/6 (16.7%)	1	0/6 (0%)	0
Psychiatric disorders
Anxiety	1/6 (16.7%)	1	0/6 (0%)	0
Depression	0/6 (0%)	0	1/6 (16.7%)	1
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	2/6 (33.3%)	2	0/6 (0%)	0
Cough	1/6 (16.7%)	1	0/6 (0%)	0
Nasal congestion	1/6 (16.7%)	1	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	1/6 (16.7%)	1	0/6 (0%)	0
Night sweats	1/6 (16.7%)	1	0/6 (0%)	0
Urticaria	1/6 (16.7%)	1	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.