CONSIDER: Canakinumab for Treatment of Adult-onset Still's Disease

• Sponsor: Charite University, Berlin, Germany (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02204293
• Collaborator: (none)
• Enrollment: 36
• Locations: 14
• Arms: 2
• Actual Duration (Months): 70.4
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this trial is to investigate the efficacy of the treatment with canakinumab in participants with Adult-onset Still's Disease (AOSD) and active joint involvement.

Condition or Disease	Intervention/Treatment	Phase
Adult-Onset Still´s Disease	Drug: Canakinumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Study Protocol for a Multi-Centre, Placebo-Controlled Phase II Study of Canakinumab for the Treatment of Adult-onset Still's Disease (AOSD) Including an Open-label Long Term Extension
• Actual Study Start Date: Jun 21, 2012
• Actual Primary Completion Date: May 5, 2018
• Actual Study Completion Date: May 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Canakinumab Participants received canakinumab 4 mg/kg up to a maximum of 300 mg subcutaneous (SC) injection, once in morning on Day 0, Weeks 4, 8, and 12 in Part I of the core study. Participants with response (change in DAS score > 1.2 at Week 12) continued to receive same dose of canakinumab in Part II for Weeks 12, 16, and 20. Participants who had remission (change in DAS score > 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) entered Long-term extension (LTE) phase and received same dose of canakinumab at Weeks 24 and 28, which was down titrated to 2 mg/kg if applicable from Week 28 up to Month 27.	Drug: Canakinumab; Canakinumab, single-dose 4 mg/kg up to 300 mg administered subcutaneously.; Other Names: Ilaris
Placebo Comparator: Placebo Participants received placebo, SC injection, once in morning on Day 0, Weeks 4, 8, and 12 in Part I of the core study. Participants with response (change in DAS score > 1.2 at Week 12) continued to receive placebo at Weeks 12, 16, and 20. Non-responders (who had change in DAS score ≤ 1.2) were unblinded to receive canakinumab 4 mg/kg (up to 300 mg maximum), SC injection, at Weeks 12, 16, and 20. Participants who had remission (change in DAS score > 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) entered Long-term extension (LTE) phase and received same dose of canakinumab at Weeks 24 and 28, which was down titrated to 2 mg/kg if applicable from Week 28 up to Month 27.	Drug: Canakinumab; Canakinumab, single-dose 4 mg/kg up to 300 mg administered subcutaneously.; Other Names: Ilaris ; Drug: Placebo; Matching placebo administered subcutaneously.

Outcome Measures

Primary Outcome Measures

1. Core Study Part I: Percentage of Responders as Assessed by Disease Activity Score 28 Joints (DAS28) Score at Week 12 [Week 12]

   Responders included participants with change in disease activity score based on 28 joint counts and ESR (DAS28) score > 1.2. The DAS28 score index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity score, and the erythrocyte sedimentation rate (ESR) value. Total score ranged between 0-10. A DAS28-ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value < 2.6 = disease remission.

Secondary Outcome Measures

1. Core Study Part I: Change From Baseline (CFB) in Disease Activity Score 28 Joints Erythrocyte Sedimentation Rate (DAS28 [ESR]) Score [Baseline, Weeks 4, 8 and 12]

   The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity score, and ESR value.Total score ranged between 0-10. A DAS28-ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value < 2.6 = disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. Least squares (LS) mean was calculated by mixed linear model for repeated measures (MMRM) analyses.

2. Core Study Part I: CFB in DAS28 C-reactive Protein (CRP) Score [Baseline, Weeks 4, 8 and 12]

   The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity score, and CRP value. Total score ranged between 0-10. A DAS28-CRP score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value < 2.6 = disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. LS mean was calculated by MMRM analyses.

3. Core Study Part I: CFB in American College of Rheumatology (ACR) Component: 68 Tender Joint Count (TJC) [Baseline, Weeks 4, 8 and 12]

   The 68 TJC included the 8 distal interphalangeal (IP), 10 proximal IP and 10 metacarpophalangeal (MTP) joints of hands, the 10 MTP and 10 proximal IP joints of feet, the 2 wrists, 2 elbows, 2 shoulders, 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 hip, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Joint tenderness was graded present (1) or absent (0). Total score is calculated by adding the scores, which range from 0 (no tender joint) to 68 (all tender joints). Lower scores indicate no tender joint and higher scores indicate worsening tender joints. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.

4. Core Study Part I: CFB in ACR Component: 66 Swollen Joint Count (SJC) [Baseline, Weeks 4, 8 and 12]

   The 66 SJC included the 8 distal interphalangeal (IP), 10 proximal IP and 10 metacarpophalangeal (MTP) joints of hands, the 10 MTP and 10 proximal IP joints of feet, the 2 wrists, 2 elbows, 2 shoulders, 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Swelling was graded present (1) or absent (0). Total score is calculated by adding the scores, which range from 0 (no swollen joint) to 66 (all swollen joints). Lower scores indicate no swollen joint and higher scores indicate worsening swollen joints. A negative change in Baseline indicates improvement. LS mean was calculated by MMRM analyses.

5. Core Study Part I: CFB in the 28 TJC [Baseline, Weeks 4, 8 and 12]

   A total of 28 joints were assessed for tenderness. The number of tender joints could range from 0 to 28, where higher values represented more tender joints. The change from Baseline to any time points was averaged among all participants, where negative changes indicated an improvement in disease activity. LS mean was calculated by MMRM analyses.

6. Core Study Part I: CFB in the 28 SJC [Baseline, Weeks 4, 8 and 12]

   A total of 28 joints were assessed for swelling. The number of swollen joints could range from 0 to 28, where higher values represented more swollen joints. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity. LS mean was calculated by MMRM analyses.

7. Core Study Part I: CFB in ACR Component: Acute Phase Reactant CRP [Baseline, Weeks 4, 8 and 12]

   A negative change from Baseline in CRP level indicates an improvement. LS mean was calculated by MMRM analyses.

8. Core Study Part I: CFB in ACR Component: Acute Phase Reactant ESR [Baseline, Weeks 4, 8 and 12]

   A negative change from Baseline in ESR level indicates an improvement. LS mean was calculated by MMRM analyses.

9. Core Study Part I: CFB in Serum Ferritin Level at Week 12 [Week 12]

   LS mean was calculated by MMRM analyses.

10. Core Study Part I: Percentage of Responders With Fever Episodes [Week 12]

    Fever is defined as an oral or rectal body temperature greater than 38 degrees Celsius (°C).

11. Core Study Part I: CFB in ACR Component: Physician's Global Assessment of Disease Activity Score [Baseline, Weeks 4, 8 and 12]

    The physician's global assessment of disease activity was assessed using a numerical rating scale of 0-10 where 0= no disease activity and 10= activity to maximal disease activity. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.

12. Core Study Part I: CFB in ACR Component: Participant's Global Assessment of Disease Activity Score [Baseline, Weeks 4, 8 and 12]

    The participant's global assessment of disease activity was assessed using a numerical rating scale of 0-10, where 0= no disease activity and 10= maximal disease activity. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.

13. Core Study Part I: CFB in ACR Component: Participant's Global Assessment of Pain Score [Baseline, Weeks 4, 8 and 12]

    The participant's global assessment of pain was assessed using a numerical rating scale of 0-10, where 0= no disease activity and 10= maximal disease activity. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.

14. Core Study Part I: CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score [Baseline, Week 12]

    The HAQ measures physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects and dollar costs. The HAQ score is calculated by summing the computed scores for each category and dividing by the number of categories answered. It ranges from 0 (without any difficulty) to 3 (unable to do). A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.

15. Core Study Part I: Percentage of Responders With American College of Rheumatology Response of 20 (ACR20) [Baseline, Week 12]

    ACR20 response was defined as a ≥ 20% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.

16. Core Study Part I: Percentage of Responders With ACR30 [Baseline, Week 12]

    ACR30 response was defined as a ≥ 30% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.

17. Core Study Part I: Percentage of Responders With Modified ACR30 [Baseline, Week 12]

    A participant was considered responder if he/she had achieved the incidence of modified adapted response (ACR30 criteria) of at least a 30% improvement in no intermittent fever and had at least 30% improvement in at least 6 of the following 7 measures: tender and swollen 68-joint counts, participant's assessment of pain, participant's global assessment of disease activity, physician's global assessment of disease activity, participant's functional capacity (HAQ-DI score) and acute phase reactant- ESR. Participant were modified ACR30 responders at a given post-randomization visit if they satisfied the modified ACR30 criteria, respectively.

18. Core Study Part I: Percentage of Responders With ACR50 [Baseline, Week 12]

    ACR50 response was defined as a ≥ 50% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.

19. Core Study Part I: Percentage of Responders With ACR70 [Baseline, Week 12]

    ACR70 response was defined as a ≥ 70% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.

20. Core Study Part I: Percentage of Responders With ACR90 [Baseline, Week 12]

    ACR90 response was defined as a ≥ 90% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.

21. Core Study Part I: Percentage of Responders With European League Against Rheumatism (EULAR) Response [Baseline, Week 12]

    EULAR response is based on DAS28-ESR and DAS28-CRP scores. The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, subject global assessment of disease activity score, and ESR or CRP value. A DAS28-CRP or ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value < 2.6 = disease remission. EULAR response has 3 categories: EULAR Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2 or EULAR No response: DAS28 >5.1 or a change from Baseline < -0.6 to ≤ -1.2.

22. Core Study Part I: Percentage of Responders Achieving Low Disease Activity (LDA) [Week 12]

    Percentage of responders were defined as the participants who achieved LDA (DAS28 score < 3.2) at Week 12. The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, participant global assessment of disease activity score, and ESR or CRP value. Total score ranged between 0-10. A DAS28 score greater than 5.1 implies high disease activity, equal to or less than 3.2 low disease activity, and less than 2.6 remissions.

23. Core Study Part I: Percentage of Responders Achieving Disease Remission and Extended Disease Remission [Week 12]

    Participants with disease remission: LDA (DAS28 score< 2.6). The DAS28 index is a composite score of weighted components including both 28 TJC an SJC, participant global assessment of disease activity score, and ESR or CRP value. A DAS28 score greater than 5.1: high disease activity, ≤ 3.2: low disease activity, and less than 2.6: remission. Extended remission criteria included DAS28 < 2.6 and no signs of systemic activity for up to two consecutive study visits till Week 12 defined as any of Yamaguchi´s primary classification criteria for AOSD which included fever attacks at 39 °C for more than a week, arthralgia, salmon red, maculate, urticarial or maculo-papular rash and leukocytosis (white blood cells increase) of > 10000/cubic millimeters (mm^3) with > 80% neutrophils.

24. Core Study Part I: Change in Joint Mobility (Degrees of Motion) Assessed by Neutral Zero Method [Baseline, Week 12]

    Number of joints with limitation of motion according to neutral zero method was assessed which included mobility of joints (elbows, wrists, shoulder joints, hip joints, knee joints, and upper ankle joints) within the reference range/degree. Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from Baseline. A negative change score indicates improvement. LS mean was calculated by MMRM analyses.

25. Core Study Part I: CFB in Medical Outcome Short Form (SF-36) Health Survey Score [Baseline, Week 12]

    The SF-36 determines overall quality of life assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 contribute to physical component summary score (PCS). Items 5-8 contribute to mental component summary score (MCS). Scores on each item are summed and averaged (range = 0 "worst"-100 "best"). Positive numbers indicate improvement from Baseline. LS mean was calculated by MMRM analyses.

26. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to Month 27]

    An AE is an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. AEs include symptoms of illnesses, as well as every unfavourable and unintended reaction. SAEs are AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Written and signed consent from the participant to take part in the study

2. Men and women aged ≥ 18 years and ≤ 75 years

3. Fulfilment of AOSD classification criteria (according to Yamaguchi et al, J. Rheumatology, 1992)

4. Disease activity based on Disease Activity Score 28 (DAS28) of ≥3.2 at screening

5. At least 4 painful and 4 swollen joints at screening and baseline (of the 28 joints according to DAS28)

6. If undergoing treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable dose for at least 4 weeks prior to randomisation

7. If undergoing treatment with glucocorticoids, stable dose of ≤10 milligrams per day (mg/day) (prednisolone or equivalent) for at least 4 weeks prior to randomisation

8. If undergoing treatment with conventional disease-modifying anti-rheumatic drugs (DMARD), stable dose for at least 3 months prior to randomisation

9. Normalisation period for biological DMARDS (anakinra 1 week, etanercept 1 month, adalimumab and certolizumab 2 months, infliximab, golimumab, abatacept and tocilizumab 3 months, rituximab 9 months, canakinumab 6 months) prior to randomisation

10. In participants of reproductive age, use of an effective method of contraception as well as negative pregnancy test prior to the study commencing.

Exclusion Criteria:

1. Previous treatment with the study drug with repeated administration of canakinumab

2. Intraarticular or intravenous administration of glucocorticoids within 4 weeks prior to the baseline or use of narcotic analgesics except for analgesics permitted within the framework of the investigation (codeine and tramadol)

3. Presence of another, serious chronic-inflammatory disease

4. Positive hepatitis B antigen (HBsAg), hepatitis C antibodies and/or human immunodeficiency virus (HIV) antibodies.

5. Presence of a relevant, active infection or other diseases, which entail a tendency towards infection

6. Positive screening for latent tuberculosis, in accordance with usual local practice

7. Raised liver count (raised bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3-fold the normal range)

8. Serum-creatinine concentration >1.5 milligrams per deciliter (mg/dL)

9. Inadequate haematological findings (hemoglobin [Hb] ≤ 10 grams per deciliter (g/dL), neutrophils ≤2,500/microliter (µl) and thrombocytes ≤100,000/µl)

10. Simultaneous participation in any other interventional clinical study within the last 30 days preceding the commencement of the study

11. History of neoplasia with the exception of a curatively treated non-melanoma skin tumour or carcinoma of the cervix treated in situ without any indication of recurrence within the last 10 years

12. Relevant cardiac or pulmonary disorders

13. Severe intercurrent neurological or psychiatric disorders

14. Macrophage activation syndrome (MAS) as part of previous treatment with IL-1 blockade (e.g. anakinra, rilonacept)

15. Vaccination with a live vaccine within 3 months before the baseline

16. Alcohol or drug abuse in the past 12 months

17. ≥400 milliliter (mL) donation of blood or loss up to 8 weeks before the baseline

18. Pregnancy or breast-feeding

19. Commitment of the patient to an institution at the direction of an authority or court

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Charité Campus Mitte	Berlin		Germany	10117
2	Immanuel Krankenhaus Berlin	Berlin		Germany	13125
3	Universität Erlangen	Erlangen		Germany	91054
4	Kliniken Essen-Süd/Krankenhaus St. Josef	Essen		Germany	45239
5	Universitätsklinikum der J.W. Goethe-Universität Frankfurt	Frankfurt a. M.		Germany	60590
6	Asklepios Klinikum Hamburg Altona	Hamburg		Germany	22763
7	Medizinische Hochschule Hannover	Hannover		Germany	30625
8	Universitätsklinikum Heidelberg	Heidelberg		Germany	69120
9	Universitätskrankenhaus Schleswig Holstein	Kiel		Germany	24105
10	Med. Klinik I für Innere Medizin Köln	Köln		Germany	50937
11	Klinikum der Universität München	München		Germany	80336
12	Klinikum Südstadt Rostock	Rostock		Germany	18059
13	Universitätsklinikum Tübingen	Tübingen		Germany	72076
14	Fachkrankenhaus	Vogelsang		Germany	39245

Sponsors and Collaborators

• Charite University, Berlin, Germany

Investigators

• Principal Investigator: Eugen Feist, Prof. Dr., Charité University Berlin Germany

Study Documents (Full-Text)

• Study Protocol - Oct 20, 2017
• Statistical Analysis Plan - May 9, 2018

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Eugen Feist, Prof. Dr Eugen Feist, Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT02204293
• Other Study ID Numbers: CACZ885GDE01T; 2011-001027-20
• First Posted: Jul 30, 2014
• Last Update Posted: Aug 7, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eugen Feist, Prof. Dr Eugen Feist, Charite University, Berlin, Germany: Adult-Onset Still´s Disease; Canakinumab; Joint involvement; AOSD
• Additional relevant MeSH terms: Arthritis, Juvenile; Still's Disease, Adult-Onset

Study Results

Participant Flow

Recruitment Details	Participants with adult-onset Still's disease (AOSD) took part in the study from June 21, 2012 to May 5, 2018 at 14 investigative sites located in Germany to participate in two double-blind parts - Part I (Up to Week 12) and Part II (Up to Week 24) and one open-label Long-Term Extension (LTE) phase (Up to Month 27).
Pre-assignment Detail	A total of 36 participants entered in Part I to receive canakinumab/placebo. Out of 31, 5 participants from canakinumab arm, and 3 from placebo arm did not enter Part II, 23 participants entered Part II and received canakinumab or placebo up to Week 24. 7 participants who achieved clinical remission entered LTE Phase to receive canakinumab.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo	Core Study Part II: Canakinumab Responders	Core Study Part II: Placebo Responders	Core Study Part II: Placebo Non-responders	LTE Phase: Canakinumab
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants with response (change in DAS score > 1.2 at Week 12) continued to receive canakinumab 4 mg/kg up to 300 mg maximum, SC injection, once in the morning for Weeks 12, 16, and 20.	Participants with response (change in DAS score > 1.2 at Week 12) continued to receive placebo, SC injection, once in morning for Weeks 12, 16, and 20.	Placebo Non-responders (change in DAS score ≤ 1.2 at Week 12) who switched to canakinumab were unblinded to receive canakinumab 4 mg/kg up to 300 mg maximum, SC injection, once in the morning at Weeks 12, 16, and 20.	Participants with remission (change in DAS score > 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) received canakinumab 4 mg/kg up to 300 mg maximum, SC injection at Weeks 24 and 28, which was down titrated to 2 mg/kg up to 150 mg maximum if applicable after Week 28 up to Month 27 (Week 117).
Period Title: Core Study Part I
STARTED	19	17	0	0	0	0
Intention-to-treat Population	18	17	0	0	0	0
Safety Population	20	15	0	0	0	0
COMPLETED	17	14	0	0	0	0
NOT COMPLETED	2	3	0	0	0	0
Period Title: Core Study Part I
STARTED	0	0	12	4	7	0
Safety Population	0	0	14	2	7	0
COMPLETED	0	0	12	4	7	0
NOT COMPLETED	0	0	0	0	0	0
Period Title: Core Study Part I
STARTED	0	0	0	0	0	7
COMPLETED	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	7

Baseline Characteristics

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo	Total
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Total of all reporting groups
Overall Participants	18	17	35
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.06 (13.2)	40.53 (13.2)	40.79 (13.2)
Sex: Female, Male (Count of Participants)
Female	10 55.6%	13 76.5%	23 65.7%
Male	8 44.4%	4 23.5%	12 34.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Core Study Part I: Percentage of Responders as Assessed by Disease Activity Score 28 Joints (DAS28) Score at Week 12
Description	Responders included participants with change in disease activity score based on 28 joint counts and ESR (DAS28) score > 1.2. The DAS28 score index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity score, and the erythrocyte sedimentation rate (ESR) value. Total score ranged between 0-10. A DAS28-ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value < 2.6 = disease remission.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Number (95% Confidence Interval) [percentage of participants]	66.7 370.6%	41.2 242.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.1811
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Core Study Part I: Change From Baseline (CFB) in Disease Activity Score 28 Joints Erythrocyte Sedimentation Rate (DAS28 [ESR]) Score
Description	The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity score, and ESR value.Total score ranged between 0-10. A DAS28-ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value < 2.6 = disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. Least squares (LS) mean was calculated by mixed linear model for repeated measures (MMRM) analyses.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	5.37	5.3
CFB at Week 4	3.56	4.27
CFB at Week 8	2.86	3.92
CFB at Week 12	3.1	4.0

3. Secondary Outcome

Title	Core Study Part I: CFB in DAS28 C-reactive Protein (CRP) Score
Description	The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity score, and CRP value. Total score ranged between 0-10. A DAS28-CRP score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value < 2.6 = disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	5.0	5.07
CFB at Week 4	3.4	4.01
CFB at Week 8	2.8	3.81
CFB at Week 12	3.31	4.01

4. Secondary Outcome

Title	Core Study Part I: CFB in American College of Rheumatology (ACR) Component: 68 Tender Joint Count (TJC)
Description	The 68 TJC included the 8 distal interphalangeal (IP), 10 proximal IP and 10 metacarpophalangeal (MTP) joints of hands, the 10 MTP and 10 proximal IP joints of feet, the 2 wrists, 2 elbows, 2 shoulders, 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 hip, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Joint tenderness was graded present (1) or absent (0). Total score is calculated by adding the scores, which range from 0 (no tender joint) to 68 (all tender joints). Lower scores indicate no tender joint and higher scores indicate worsening tender joints. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	8.89	11.18
CFB at Week 4	5.33	5.85
CFB at Week 8	3.72	5.1
CFB at Week 12	4.66	6.9

5. Secondary Outcome

Title	Core Study Part I: CFB in ACR Component: 66 Swollen Joint Count (SJC)
Description	The 66 SJC included the 8 distal interphalangeal (IP), 10 proximal IP and 10 metacarpophalangeal (MTP) joints of hands, the 10 MTP and 10 proximal IP joints of feet, the 2 wrists, 2 elbows, 2 shoulders, 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Swelling was graded present (1) or absent (0). Total score is calculated by adding the scores, which range from 0 (no swollen joint) to 66 (all swollen joints). Lower scores indicate no swollen joint and higher scores indicate worsening swollen joints. A negative change in Baseline indicates improvement. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	5.78	8.0
CFB at Week 4	2.5	2.5
CFB at Week 8	1.33	2.65
CFB at Week 12	2.89	4.71

6. Secondary Outcome

Title	Core Study Part I: CFB in the 28 TJC
Description	A total of 28 joints were assessed for tenderness. The number of tender joints could range from 0 to 28, where higher values represented more tender joints. The change from Baseline to any time points was averaged among all participants, where negative changes indicated an improvement in disease activity. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	6.78	7.24
CFB at Week 4	3.67	4.29
CFB at Week 8	2.39	3.85
CFB at Week 12	3.47	4.43

7. Secondary Outcome

Title	Core Study Part I: CFB in the 28 SJC
Description	A total of 28 joints were assessed for swelling. The number of swollen joints could range from 0 to 28, where higher values represented more swollen joints. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	4.97	6.29
CFB at Week 4	2.11	2.47
CFB at Week 8	0.83	2.79
CFB at Week 12	2.28	4.51

8. Secondary Outcome

Title	Core Study Part I: CFB in ACR Component: Acute Phase Reactant CRP
Description	A negative change from Baseline in CRP level indicates an improvement. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	45.55	57.26
CFB at Week 4	17.53	36.74
CFB at Week 8	14.61	32.51
CFB at Week 12	17.05	28.52

9. Secondary Outcome

Title	Core Study Part I: CFB in ACR Component: Acute Phase Reactant ESR
Description	A negative change from Baseline in ESR level indicates an improvement. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	44.11	38.82
CFB at Week 4	24.28	38.6
CFB at Week 8	25.4	25.25
CFB at Week 12	15.85	22.41

10. Secondary Outcome

Title	Core Study Part I: CFB in Serum Ferritin Level at Week 12
Description	LS mean was calculated by MMRM analyses.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	17	14
Least Squares Mean (95% Confidence Interval) [nanograms per milliliter (ng/mL)]	466.9	634.71

11. Secondary Outcome

Title	Core Study Part I: Percentage of Responders With Fever Episodes
Description	Fever is defined as an oral or rectal body temperature greater than 38 degrees Celsius (°C).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Number [percentage of participants]	8.3 46.1%	0 0%

12. Secondary Outcome

Title	Core Study Part I: CFB in ACR Component: Physician's Global Assessment of Disease Activity Score
Description	The physician's global assessment of disease activity was assessed using a numerical rating scale of 0-10 where 0= no disease activity and 10= activity to maximal disease activity. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	5.5	6.0
CFB at Week 4	3.06	3.67
CFB at Week 8	2.72	3.56
CFB at Week 12	2.86	4.26

13. Secondary Outcome

Title	Core Study Part I: CFB in ACR Component: Participant's Global Assessment of Disease Activity Score
Description	The participant's global assessment of disease activity was assessed using a numerical rating scale of 0-10, where 0= no disease activity and 10= maximal disease activity. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	6.08	5.85
CFB at Week 4	3.78	4.74
CFB at Week 8	2.84	4.58
CFB at Week 12	3.63	4.32

14. Secondary Outcome

Title	Core Study Part I: CFB in ACR Component: Participant's Global Assessment of Pain Score
Description	The participant's global assessment of pain was assessed using a numerical rating scale of 0-10, where 0= no disease activity and 10= maximal disease activity. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	6.61	6.35
CFB at Week 4	3.61	4.85
CFB at Week 8	2.73	4.18
CFB at Week 12	3.71	4.25

15. Secondary Outcome

Title	Core Study Part I: CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Description	The HAQ measures physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects and dollar costs. The HAQ score is calculated by summing the computed scores for each category and dividing by the number of categories answered. It ranges from 0 (without any difficulty) to 3 (unable to do). A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	1.31	1.29
CFB at Week 12	0.69	0.98

16. Secondary Outcome

Title	Core Study Part I: Percentage of Responders With American College of Rheumatology Response of 20 (ACR20)
Description	ACR20 response was defined as a ≥ 20% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Number (95% Confidence Interval) [percentage of participants]	61.1 339.4%	41.2 242.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.3175
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	19.9
	Confidence Interval	(2-Sided) 95%; -15.0 to 51.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Core Study Part I: Percentage of Responders With ACR30
Description	ACR30 response was defined as a ≥ 30% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Number (95% Confidence Interval) [percentage of participants]	61.1 339.4%	29.4 172.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.0922
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	31.7
	Confidence Interval	(2-Sided) 95%; -2.9 to 61.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Core Study Part I: Percentage of Responders With Modified ACR30
Description	A participant was considered responder if he/she had achieved the incidence of modified adapted response (ACR30 criteria) of at least a 30% improvement in no intermittent fever and had at least 30% improvement in at least 6 of the following 7 measures: tender and swollen 68-joint counts, participant's assessment of pain, participant's global assessment of disease activity, physician's global assessment of disease activity, participant's functional capacity (HAQ-DI score) and acute phase reactant- ESR. Participant were modified ACR30 responders at a given post-randomization visit if they satisfied the modified ACR30 criteria, respectively.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Number (95% Confidence Interval) [percentage of participants]	55.6 308.9%	23.5 138.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.0858
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	32.0
	Confidence Interval	(2-Sided) 95%; -1.5 to 61.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Core Study Part I: Percentage of Responders With ACR50
Description	ACR50 response was defined as a ≥ 50% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Number (95% Confidence Interval) [percentage of participants]	50.0 277.8%	17.6 103.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.075
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	32.4
	Confidence Interval	(2-Sided) 95%; -0.7 to 60.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Core Study Part I: Percentage of Responders With ACR70
Description	ACR70 response was defined as a ≥ 70% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Number (95% Confidence Interval) [percentage of participants]	27.8 154.4%	11.8 69.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.4018
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	16.0
	Confidence Interval	(2-Sided) 95%; -12.6 to 43.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Core Study Part I: Percentage of Responders With ACR90
Description	ACR90 response was defined as a ≥ 90% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Number (95% Confidence Interval) [percentage of participants]	11.1 61.7%	5.9 34.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	5.2
	Confidence Interval	(2-Sided) 95%; -18.8 to 29.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Core Study Part I: Percentage of Responders With European League Against Rheumatism (EULAR) Response
Description	EULAR response is based on DAS28-ESR and DAS28-CRP scores. The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, subject global assessment of disease activity score, and ESR or CRP value. A DAS28-CRP or ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value < 2.6 = disease remission. EULAR response has 3 categories: EULAR Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2 or EULAR No response: DAS28 >5.1 or a change from Baseline < -0.6 to ≤ -1.2.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
EULAR DAS28-ESR Response	77.8 432.2%	52.9 311.2%
EULAR DAS28-CRP Response	72.2 401.1%	47.1 277.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments	EULAR DAS28-ESR Response
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.1642
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	24.8
	Confidence Interval	(2-Sided) 95%; -8.0 to 54.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments	EULAR DAS28-CRP Response
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.1756
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	25.2
	Confidence Interval	(2-Sided) 95%; -9.1 to 55.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Core Study Part I: Percentage of Responders Achieving Low Disease Activity (LDA)
Description	Percentage of responders were defined as the participants who achieved LDA (DAS28 score < 3.2) at Week 12. The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, participant global assessment of disease activity score, and ESR or CRP value. Total score ranged between 0-10. A DAS28 score greater than 5.1 implies high disease activity, equal to or less than 3.2 low disease activity, and less than 2.6 remissions.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
DAS28 (ESR) LDA	33.3 185%	29.4 172.9%
DAS28 (CRP) LDA	50.0 277.8%	23.5 138.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments	DAS28 (ESR) LDA
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	3.9
	Confidence Interval	(2-Sided) 95%; -27.7 to 35.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments	DAS28 (CRP) LDA
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.1642
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	26.5
	Confidence Interval	(2-Sided) 95%; -6.6 to 56.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Core Study Part I: Percentage of Responders Achieving Disease Remission and Extended Disease Remission
Description	Participants with disease remission: LDA (DAS28 score< 2.6). The DAS28 index is a composite score of weighted components including both 28 TJC an SJC, participant global assessment of disease activity score, and ESR or CRP value. A DAS28 score greater than 5.1: high disease activity, ≤ 3.2: low disease activity, and less than 2.6: remission. Extended remission criteria included DAS28 < 2.6 and no signs of systemic activity for up to two consecutive study visits till Week 12 defined as any of Yamaguchi´s primary classification criteria for AOSD which included fever attacks at 39 °C for more than a week, arthralgia, salmon red, maculate, urticarial or maculo-papular rash and leukocytosis (white blood cells increase) of > 10000/cubic millimeters (mm^3) with > 80% neutrophils.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
DAS28 (ESR) Remission	33.3 185%	11.8 69.4%
DAS28 (CRP) Remission	38.9 216.1%	11.8 69.4%
Extended Remission	27.8 154.4%	11.8 69.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments	DAS28 (ESR) remission
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.2285
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	21.6
	Confidence Interval	(2-Sided) 95%; -8.1 to 49.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments	DAS28 (CRP) Remission
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.1212
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	27.1
	Confidence Interval	(2-Sided) 95%; -4.6 to 54.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Study Part I: Canakinumab, Core Study Part I: Placebo
	Comments	Extended Remission
	Type of Statistical Test	Superiority
	Comments	Fisher's exact test with a two-tailed level of significance of α = 0.05.
Statistical Test of Hypothesis	p-Value	0.4018
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	16.0
	Confidence Interval	(2-Sided) 95%; -12.6 to 43.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Core Study Part I: Change in Joint Mobility (Degrees of Motion) Assessed by Neutral Zero Method
Description	Number of joints with limitation of motion according to neutral zero method was assessed which included mobility of joints (elbows, wrists, shoulder joints, hip joints, knee joints, and upper ankle joints) within the reference range/degree. Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from Baseline. A negative change score indicates improvement. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
Baseline	4.94	6.29
Week 12	5.37	6.05

26. Secondary Outcome

Title	Core Study Part I: CFB in Medical Outcome Short Form (SF-36) Health Survey Score
Description	The SF-36 determines overall quality of life assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 contribute to physical component summary score (PCS). Items 5-8 contribute to mental component summary score (MCS). Scores on each item are summed and averaged (range = 0 "worst"-100 "best"). Positive numbers indicate improvement from Baseline. LS mean was calculated by MMRM analyses.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.
Measure Participants	18	17
SF-36 Physical: Baseline	29.39	28.73
SF-36 Physical: CFB at Week 12	41.03	33.45
SF-36 Mental: Baseline	37.8	46.31
SF-36 Mental: CFB at Week 12	43.47	49.82

27. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE is an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. AEs include symptoms of illnesses, as well as every unfavourable and unintended reaction. SAEs are AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Time Frame	Up to Month 27

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included all participants randomized who received at least one dose of the study drug.

Arm/Group Title	Core Study Part I: Canakinumab	Core Study Part I: Placebo	Core Study Part II: Canakinumab Responders	Core Study Part II: Placebo Responders	Core Study Part II: Placebo Non-responders	LTE Phase: Canakinumab
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.	Participants with response (change in DAS score > 1.2 at Week 12) continued to receive canakinumab 4 mg/kg up to 300 mg maximum, SC injection, once in the morning for Weeks 12, 16, and 20.	Participants with response (change in DAS score > 1.2 at Week 12) continued to receive placebo, SC injection, once in morning for Weeks 12, 16, and 20.	Placebo Non-responders (change in DAS score ≤ 1.2 at Week 12) who switched to canakinumab were unblinded to receive canakinumab 4 mg/kg up to 300 mg maximum, SC injection, once in the morning at Weeks 12, 16, and 20.	Participants with remission (change in DAS score > 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) received canakinumab 4 mg/kg up to 300 mg maximum, SC injection at Weeks 24 and 28, which was down titrated to 2 mg/kg up to 150 mg maximum if applicable after Week 28 up to Month 27 (Week 117).
Measure Participants	20	15	14	2	7	7
AEs	16 88.9%	10 58.8%	13 37.1%	2 NaN	6 NaN	7 NaN
SAEs	2 11.1%	0 0%	1 2.9%	1 NaN	1 NaN	1 NaN

Adverse Events

Time Frame	Up to Month 27
Adverse Event Reporting Description	Safety Analysis Set included all participants randomized who received at least one dose of the study drug. 2 participants of the placebo group in Part I received canakinumab at Week 4, as protocol violation, thus, Safety Analysis Set included those additional 2 participants in the canakinumab group.
Arm/Group Title	Core Study Part I: Canakinumab		Core Study Part I: Placebo		Core Study Part II: Canakinumab Responders		Core Study Part II: Placebo Responders		Core Study Part II: Placebo Non-responders		LTE Phase: Canakinumab
Arm/Group Description	Participants received canakinumab 4 mg/kg up to 300 mg maximum, subcutaneous (SC) injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.		Participants received placebo, SC injection, once in morning at Baseline (Day 0), Weeks 4, 8, and 12.		Participants with response (change in DAS score > 1.2 at Week 12) continued to receive canakinumab 4 mg/kg up to 300 mg maximum, SC injection, once in the morning for Weeks 12, 16, and 20.		Participants with response (change in DAS score > 1.2 at Week 12) continued to receive placebo, SC injection, once in morning for Weeks 12, 16, and 20.		Placebo Non-responders (change in DAS score ≤ 1.2 at Week 12) who switched to canakinumab were unblinded to receive canakinumab 4 mg/kg up to 300 mg maximum, SC injection, once in the morning at Weeks 12, 16, and 20.		Participants with remission (change in DAS score > 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) received canakinumab 4 mg/kg up to 300 mg maximum, SC injection at Weeks 24 and 28, which was down titrated to 2 mg/kg up to 150 mg maximum if applicable after Week 28 up to Month 27 (Week 117).
All Cause Mortality
	Core Study Part I: Canakinumab		Core Study Part I: Placebo		Core Study Part II: Canakinumab Responders		Core Study Part II: Placebo Responders		Core Study Part II: Placebo Non-responders		LTE Phase: Canakinumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Serious Adverse Events
	Core Study Part I: Canakinumab		Core Study Part I: Placebo		Core Study Part II: Canakinumab Responders		Core Study Part II: Placebo Responders		Core Study Part II: Placebo Non-responders		LTE Phase: Canakinumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/20 (10%)		0/15 (0%)		1/14 (7.1%)		1/2 (50%)		1/7 (14.3%)		1/7 (14.3%)
Gastrointestinal disorders
Abdominal pain upper	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Hepatobiliary disorders
Cholecystitis	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Cholecystitis acute	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Hepatotoxicity	1/20 (5%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Injury, poisoning and procedural complications
Fracture	0/20 (0%)		0/15 (0%)		0/14 (0%)		1/2 (50%)		0/7 (0%)		0/7 (0%)
Hand fracture	0/20 (0%)		0/15 (0%)		0/14 (0%)		1/2 (50%)		0/7 (0%)		0/7 (0%)
Musculoskeletal and connective tissue disorders
Chondromalacia	1/20 (5%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Patellofemoral pain syndrome	1/20 (5%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Nervous system disorders
Hypotonia	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Surgical and medical procedures
Medical device removal	0/20 (0%)		0/15 (0%)		0/14 (0%)		1/2 (50%)		0/7 (0%)		0/7 (0%)
Vascular disorders
Deep vein thrombosis	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Core Study Part I: Canakinumab		Core Study Part I: Placebo		Core Study Part II: Canakinumab Responders		Core Study Part II: Placebo Responders		Core Study Part II: Placebo Non-responders		LTE Phase: Canakinumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/20 (80%)		10/15 (66.7%)		13/14 (92.9%)		2/2 (100%)		6/7 (85.7%)		7/7 (100%)
Blood and lymphatic system disorders
Lymphadenopathy	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Eye disorders
Eyelid oedema	2/20 (10%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Visual impairment	1/20 (5%)		2/15 (13.3%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Gastrointestinal disorders
Abdominal pain	1/20 (5%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Abdominal pain upper	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Aphthous ulcer	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Diarrhoea	2/20 (10%)		2/15 (13.3%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Nausea	2/20 (10%)		1/15 (6.7%)		1/14 (7.1%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
General disorders
Fatigue	1/20 (5%)		2/15 (13.3%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Influenza like illness	0/20 (0%)		1/15 (6.7%)		2/14 (14.3%)		0/2 (0%)		0/7 (0%)		3/7 (42.9%)
Injection site rash	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Pyrexia	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Hepatobiliary disorders
Primary biliary cholangitis	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Infections and infestations
Bronchitis	0/20 (0%)		1/15 (6.7%)		1/14 (7.1%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Gastrointestinal infection	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Hand-foot-and-mouth disease	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Herpes zoster	0/20 (0%)		1/15 (6.7%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Infected bite	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Nasopharyngitis	3/20 (15%)		3/15 (20%)		3/14 (21.4%)		0/2 (0%)		1/7 (14.3%)		3/7 (42.9%)
Oral herpes	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Otitis media	0/20 (0%)		1/15 (6.7%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Periodontitis	0/20 (0%)		0/15 (0%)		0/14 (0%)		1/2 (50%)		0/7 (0%)		0/7 (0%)
Pertussis	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Respiratory tract infection	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Rhinitis	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Tooth abscess	0/20 (0%)		1/15 (6.7%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Upper respiratory tract infection	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Urinary tract infection	0/20 (0%)		1/15 (6.7%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Injury, poisoning and procedural complications
Fall	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Meniscus injury	1/20 (5%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Investigations
Alanine aminotransferase increased	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Gamma-glutamyltransferase increased	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Hepatic enzyme increased	2/20 (10%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Transaminases increased	0/20 (0%)		0/15 (0%)		2/14 (14.3%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Metabolism and nutrition disorders
Appetite disorder	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/20 (10%)		1/15 (6.7%)		2/14 (14.3%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Back pain	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Groin pain	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Joint swelling	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Muscle spasms	0/20 (0%)		1/15 (6.7%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Myalgia	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Neck pain	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Osteoporosis	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Pain in extremity	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Pseudarthrosis	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Still's disease	5/20 (25%)		1/15 (6.7%)		2/14 (14.3%)		1/2 (50%)		1/7 (14.3%)		1/7 (14.3%)
Tenosynovitis	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Nervous system disorders
Carpal tunnel syndrome	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Dizziness	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Headache	1/20 (5%)		3/15 (20%)		1/14 (7.1%)		0/2 (0%)		2/7 (28.6%)		0/7 (0%)
Intercostal neuralgia	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Sciatica	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Psychiatric disorders
Depression	0/20 (0%)		1/15 (6.7%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Sleep disorder	1/20 (5%)		1/15 (6.7%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Renal and urinary disorders
Dysuria	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Reproductive system and breast disorders
Ovarian cyst	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Vulva cyst	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		2/7 (28.6%)
Cough	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Dysphonia	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Pleurisy	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		1/7 (14.3%)		0/7 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/20 (5%)		1/15 (6.7%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Dermatitis allergic	0/20 (0%)		1/15 (6.7%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Hyperhidrosis	0/20 (0%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		0/7 (0%)		1/7 (14.3%)
Nail dystrophy	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)
Pruritus	1/20 (5%)		0/15 (0%)		0/14 (0%)		0/2 (0%)		2/7 (28.6%)		0/7 (0%)
Rash	0/20 (0%)		0/15 (0%)		1/14 (7.1%)		1/2 (50%)		0/7 (0%)		0/7 (0%)
Vascular disorders
Haematoma	1/20 (5%)		0/15 (0%)		1/14 (7.1%)		0/2 (0%)		0/7 (0%)		0/7 (0%)

Limitations/Caveats

The study terminated prior to the planned completion date due to recruitment issues because of the marketing authorization of the study drug.

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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.