Canakinumab in Patients With Active Hyper-IgD Syndrome

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01303380
• Collaborator: (none)
• Enrollment: 9
• Locations: 3
• Arm: 1
• Duration (Months): 40
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This pilot study is designed to evaluate the efficacy, the safety, and the pharmacokinetics (PK) / pharmacodynamics (PD) of canakinumab treatment in patients with HIDS.

Condition or Disease	Intervention/Treatment	Phase
Mevalonate Kinase Deficiency	Drug: Canakinumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multicenter, Efficacy and Safety Pilot Study of 6-month Canakinumab Treatment With up to 6-month Follow-up in Patients With Active Hyper-IgD Syndrome (HIDS)
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Canakinumab	Drug: Canakinumab

Outcome Measures

Primary Outcome Measures

1. Number of Flares Per Participant During Historical Period and Treatment Period [Historical period, Month 6 (End of treatment period)]

   A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a C-reactive protein (CRP) value > 10 mg/L. Flares during a historical period were defined as most recent 6-months in which the participant has not received treatment for their HIDS other than symptomatic treatment with NSAIDs and/or corticosteroids.

Secondary Outcome Measures

1. Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period [Month 6 (End of treatment period), Month 36 (End of Long term treatment Period 2)]

   A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L.

2. Number of Participants Who Flared at Month 6, Month 24 and Month 36 [Baseline, Month 6 (End of treatment period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

   A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L.

3. Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score [Any flare event [Baseline up to Month 36 (End of long term treatment period 2)]]

   Physician global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5- point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe.

4. Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score [Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

   Participant's global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5-point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe. Same investigator assessed the same participant throughout the study to ensure consistency between assessments. Investigators reviewed every participant's diary at each visit after their own clinical assessment.

5. Percentage of Participants With Defined Grades of Participants Assessed Symptom Control [Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

   Participants were assessed by participants/parent (participants aged 6-18 years) for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control.

6. Percentage of Participants With Defined Grades of Physician Assessed Symptom Control [Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

   Participants were assessed by physician for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control.

7. Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment [Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

   Fever severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.

8. Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment [Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

   Apthus ulcers were assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.

9. Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment [Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

   Lymphadenopathy severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.

10. Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment [Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

    Abdominal pain was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.

11. Time to Resolution of the Initial Flare After First Canakinumab Treatment [Day 1 (Baseline), Day 28]

    Time to resolution of the initial flare after first dose of canakinumab was determined.

12. Change From Baseline in Inflammation Markers Over Time up to Month 24 [Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

    The C-reactive Protein (CRP) and/or Serum amyloid A protein (SAA) were used as inflammatory markers. The normal range of CRP was 0-10 mg/L.

13. Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time [Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

    Participants were assessed for health-related quality of life (HRQoL) based on Health Assessment Questionnaire (HAQ). HAQ was an eight 8 categories questionnaire representing all activities related to physical function. Each category has various sub-categories, which were rated by the participants on a 4- point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. The total score was the mean of the 8 scores, and ranged from 0 (no disability) to 3 (completely disabled).

14. Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time [Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

    Participants or their parents (participants aged 6 to 17 years) were assessed for HRQoL based on Childhood Health Assessment Questionnaire (CHAQ). CHAQ was an eight domain questionnaire representing functional capacity and independence, evaluated for previous week. Each domain was rated on a 4-point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do.The total score is the mean from the 8 scores, and ranges from 0 (no disability) to 3 (completely disabled).

15. Percentage of Participants Who Received Dose Up-titration During 6-month Treatment Period [Day 1 up to Month 6 (End of follow up)]

    Participants who experienced a new HIDS flare between baseline and Week 4 and received an escalated dose of 450 mg of canakinumab every 6 weeks thereafter starting at Week 6 were determined.

16. Duration of Flares Experienced During the Study [Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)]

    Flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. The change in post canakinumab treatment flare duration during the study were assessed as compared to historical period.

17. Time to Flare After the Last Dose of Canakinumab During the Follow-up Period [Last dose of canakinumab treatment in follow-up period to end of follow-up period (Day 337)]

    The median time to flare by the participants after administration of the last dose of canakinumab during the follow-up period was analysed using Kaplan-Meier method.

18. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 (Start of study treatment) up to Month 36 (End of study)]

    Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

19. Participants Who Received Rescue Treatment [Baseline up to Month 36 (End of study)]

    Participants who experienced flares were treated with corticosteroids and NSAIDs as rescue medication.

20. Serum Concentration-time Profile of Canakinumab [Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose)]

    Canakinumab concentrations in serum were assessed for evaluating pharmacokinetics (PK) of the drug.

21. Serum Concentration of Total Interleukin-1β Antibody (IL-1β) [Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose)]

    Pharmacodynamics of canakinumab was assessed by total IL-1β (sum of free and bound canakinumab) concentration, determined in serum by means of sandwich ELISA assay with limit of detection at 0.1 picogram/millilitre.

22. Number of Participants Exhibiting Anti-canakinumab Antibodies at Any Visit [Baseline up to Month 36 (End of study)]

    Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using bridging ECLIA assay.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 24 Months and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with a diagnosis of HIDS proven by DNA analysis and/or enzymatic studies.

2. At time of start of drug treatment: active HIDS as evidenced by a physician global assessment of HIDS flare severity ≥ 2 and CRP values >10 mg/L (normal CRP < or = 10 mg/L).

3. Patients who have a history of > or = 3 febrile acute HIDS flares in a 6-month period when not receiving prophylaxis treatment (e.g. anakinra daily treatment) with a duration of each flare lasting > or = 4 days and limiting the normal daily activities.

Exclusion Criteria:

1. Pregnant or nursing (lactating) women.

2. History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result.

3. Positive Hepatitis B or Hepatitis C.

4. Live vaccinations within 3 months prior to the start of the trial

5. Positive tuberculosis screening test.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Esplugues de Llobregat	Barcelona	Spain	08950
2	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46026
3	Novartis Investigative Site	Madrid		Spain	28046

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01303380
• Other Study ID Numbers: CACZ885D2402; 2010-020904-31
• First Posted: Feb 24, 2011
• Last Update Posted: Nov 5, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Hyper IgD syndrome; canakinumab; HIDS; mevalonate kinase deficiency; MKD
• Additional relevant MeSH terms: Mevalonate Kinase Deficiency

Study Results

Participant Flow

Recruitment Details	The study was conducted at 3 centres in Spain.
Pre-assignment Detail	A total of 10 participants were screened, 9 of which entered in the treatment period of the study, one participant was considered to be a screening failure.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new Hyper-IgD with periodic fever syndrome (HIDS) flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Period Title: Overall Study
STARTED	9
COMPLETED	8
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Overall Participants	9
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	17.3
Age, Customized (participants) [Number]
Children (2--11 years)	3 33.3%
Adolescents (12--17 years)	3 33.3%
Adults (18--64 years)	3 33.3%
Sex: Female, Male (Count of Participants)
Female	6 66.7%
Male	3 33.3%
Region of Enrollment (participants) [Number]
Spain	9 100%

Outcome Measures

1. Primary Outcome

Title	Number of Flares Per Participant During Historical Period and Treatment Period
Description	A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a C-reactive protein (CRP) value > 10 mg/L. Flares during a historical period were defined as most recent 6-months in which the participant has not received treatment for their HIDS other than symptomatic treatment with NSAIDs and/or corticosteroids.
Time Frame	Historical period, Month 6 (End of treatment period)

Outcome Measure Data

Analysis Population Description

The primary analysis was performed in the Full Analysis set (FAS) population defined as all participants who received at least one dose of study treatment and had at least one post baseline assessment.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Historical period	5
Month 6	0

2. Secondary Outcome

Title	Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period
Description	A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L.
Time Frame	Month 6 (End of treatment period), Month 36 (End of Long term treatment Period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Treatment period	0
Long term treatment period	0

3. Secondary Outcome

Title	Number of Participants Who Flared at Month 6, Month 24 and Month 36
Description	A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L.
Time Frame	Baseline, Month 6 (End of treatment period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Treatment period	2 22.2%
End of Long term treatment Period 1	4 44.4%
End of Long term treatment Period 2	2 22.2%

4. Secondary Outcome

Title	Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score
Description	Physician global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5- point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe.
Time Frame	Any flare event [Baseline up to Month 36 (End of long term treatment period 2)]

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Day 45, Absent (n=9)	0 0%
Day 45, Minimal (n=9)	0 0%
Day 45,Mild (n=9)	0 0%
Day 45,Moderate (n=9)	1 11.1%
Day 45,Severe (n=9)	0 0%
Flare/Unscheduled visit 1, Absent (n=2)	2 22.2%
Flare/Unscheduled visit 1, Minimal (n=2)	0 0%
Flare/Unscheduled visit 1, Mild (n=2)	1 11.1%
Flare/Unscheduled visit 1, Moderated (n=2)	1 11.1%
Flare/Unscheduled visit 1, Severe (n=2)	0 0%
Flare/Unscheduled visit 2, Absent (n=2)	1 11.1%
Flare/Unscheduled visit 2, Minimal (n=2)	0 0%
Flare/Unscheduled visit 2, Mild (n=2)	1 11.1%
Flare/Unscheduled visit 2, Moderate (n=2)	0 0%
Flare/Unscheduled visit 2, Severe (n=2)	0 0%
Flare/Unscheduled visit 3, Absent (n=2)	1 11.1%
Flare/Unscheduled visit 3, Minimal (n=2)	0 0%
Flare/Unscheduled visit 3, Mild (n=2)	0 0%
Flare/Unscheduled visit 3, Moderate (n=2)	1 11.1%
Flare/Unscheduled visit 3, Severe (n=2)	0 0%
End of Treatment period, Absent (n=7)	0 0%
End of Treatment period, Minimal (n=7)	0 0%
End of Treatment period, Mild (n=7)	4 44.4%
End of Treatment period, Moderate (n=7)	3 33.3%
End of Treatment period, Severe (n=7)	0 0%
End of Follow-up period, Absent (n=8)	0 0%
End of Follow-up period, Minimal (n=8)	1 11.1%
End of Follow-up period, Mild (n=8)	0 0%
End of Follow-up period, Moderate (n=8)	0 0%
End of Follow-up period, Severe (n=8)	0 0%
Long term period 1, Flare 1, Absent (n=3)	0 0%
Long term period 1, Flare 1, Minimal (n=3)	1 11.1%
Long term period 1, Flare 1, Mild (n=3)	1 11.1%
Long-term 12 M period, Flare 1, Moderate (n=3)	1 11.1%
Long-term 12 M period, Flare 1, Severe (n=3)	0 0%
Long term period 1, Flare 2, Absent (n=1)	0 0%
Long-term 12 M period, Flare 2, Minimal (n=1)	0 0%
Long-term 12 M period, Flare 2, Mild (n=1)	1 11.1%
Long term period 1, Flare 2, Moderate (n=1)	0 0%
Long term period 1, Flare 2, Severe (n=1)	0 0%
Long term period 1, Flare 3, Absent (n=1)	0 0%
Long term period 1, Flare 3, Minimal (n=1)	0 0%
Long term period 1, Flare 3, Mild (n=1)	1 11.1%
Long term period 1, Flare 3, Moderate (n=1)	0 0%
Long term period 1, Flare 3, Severe (n=1)	0 0%
Long term period 2, Absent (n=2)	1 11.1%
Long term period 2, Minimal (n=2)	0 0%
Long term period 2, Mild (n=2)	1 11.1%
Long term period 2, Moderate (n=2)	0 0%
Long term period 2, Severe (n=2)	0 0%

5. Secondary Outcome

Title	Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score
Description	Participant's global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5-point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe. Same investigator assessed the same participant throughout the study to ensure consistency between assessments. Investigators reviewed every participant's diary at each visit after their own clinical assessment.
Time Frame	Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Treatment period, Absent	0 0%
Treatment period, Minimal	0 0%
Treatment period, Mild	1 11.1%
Treatment period, Moderate	1 11.1%
Treatment period, Severe	0 0%
Follow-up period, Absent	0 0%
Follow-up period, Minimal	0 0%
Follow-up period, Mild	0 0%
Follow-up period, Moderate	2 22.2%
Follow-up period, Severe	0 0%
Long term period 1, Absent	0 0%
Long term period 1, Minimal	1 11.1%
Long term period 1, Mild	1 11.1%
Long term period 1, Moderate	2 22.2%
Long term period 1, Severe	0 0%
Long term period 2, Absent	0 0%
Long term period 2, Minimal	1 11.1%
Long term period 2, Mild	0 0%
Long term period 2, Moderate	0 0%
Long term period 2, Severe	0 0%

6. Secondary Outcome

Title	Percentage of Participants With Defined Grades of Participants Assessed Symptom Control
Description	Participants were assessed by participants/parent (participants aged 6-18 years) for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control.
Time Frame	Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Treatment period, No control (n=9)	0 0%
Treatment period, Poor control (n=9)	0 0%
Treatment period, Somewhat control (n=9)	11.11 123.4%
Treatment period, Good control (n=9)	33.33 370.3%
Treatment period, Excellent control (n=9)	55.56 617.3%
Follow-up period, No control (n=9)	0 0%
Follow-up period, Poor control (n=9)	0 0%
Follow-up period, Somewhat control (n=9)	0 0%
Follow-up period, Good control (n=9)	33.33 370.3%
Follow-up period, Excellent control (n=9)	66.67 740.8%
Long term period 1, No control (n=8)	0 0%
Long term period 1, Poor control (n=8)	0 0%
Long term period 1, Somewhat control (n=8)	12.5 138.9%
Long term period 1, Good control (n=8)	25 277.8%
Long term period 1, Excellent control (n=8)	62.5 694.4%
Long term period 2, No control (n=8)	0 0%
Long term period 2, Poor control (n=8)	0 0%
Long term period 2, Somewhat control (n=8)	0 0%
Long term period 2, Good control (n=8)	12.5 138.9%
Long term period 2, Excellent control (n=8	87.5 972.2%

7. Secondary Outcome

Title	Percentage of Participants With Defined Grades of Physician Assessed Symptom Control
Description	Participants were assessed by physician for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control.
Time Frame	Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Treatment period, No control (n=9)	0 0%
Treatment period, Poor control (n=9)	0 0%
Treatment period, Somewhat control (n=9)	0 0%
Treatment period, Good control (n=9)	44.44 493.8%
Treatment period, Excellent control (n=9)	55.56 617.3%
Follow-up period, No control (n=9)	0 0%
Follow-up period, Poor control (n=9)	0 0%
Follow-up period, Somewhat control (n=9)	0 0%
Follow-up period, Good control (n=9)	33.33 370.3%
Follow-up period, Excellent control (n=9)	66.67 740.8%
Long term period 1, No control (n=8)	0 0%
Long term period 1, Poor control (n=8)	0 0%
Long term period 1, Somewhat control (n=8)	12.5 138.9%
Long term period 1, Good control (n=8)	25 277.8%
Long term period 1, Excellent control (n=8)	62.5 694.4%
Long term period 2, No control (n=8)	0 0%
Long term period 2, Poor control (n=8)	0 0%
Long term period 2, Somewhat control (n=8)	0 0%
Long term period 2, Good control (n=8)	0 0%
Long term period 2, Excellent control (n=8	100 1111.1%

8. Secondary Outcome

Title	Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment
Description	Fever severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.
Time Frame	Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Treatment period, Absent (n=9)	88.89 987.7%
Treatment period, Minimal (n=9)	11.11 123.4%
Treatment period, Mild (n=9)	0 0%
Treatment period, Moderate (n=9)	0 0%
Treatment period, Severe (n=9)	0 0%
Follow-up period, Absent (n=9)	100 1111.1%
Follow-up period, Minimal (n=9)	0 0%
Follow-up period, Mild (n=9)	0 0%
Follow-up period, Moderate (n=9)	0 0%
Follow-up period, Severe (n=9)	0 0%
Long term period 1, Absent (n=8)	75 833.3%
Long term period 1, Minimal (n=8)	12.5 138.9%
Long term period 1, Mild (n=8)	12.5 138.9%
Long term period 1, Moderate (n=8)	0 0%
Long term period 1, Severe (n=8)	0 0%
Long term period 2, Absent (n=8)	100 1111.1%
Long term period 2, Minimal (n=8)	0 0%
Long term period 2, Mild (n=8)	0 0%
Long term period 2, Moderate (n=8)	0 0%
Long term period 2, Severe (n=8)	0 0%

9. Secondary Outcome

Title	Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment
Description	Apthus ulcers were assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.
Time Frame	Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Treatment period, Absent (n=9)	88.89 987.7%
Treatment period, Minimal (n=9)	0 0%
Treatment period, Mild (n=9)	11.11 123.4%
Treatment period, Moderate (n=9)	0 0%
Treatment period, Severe (n=9)	0 0%
Follow-up period, Absent (n=9)	100 1111.1%
Follow-up period, Minimal (n=9)	0 0%
Follow-up period, Mild (n=9)	0 0%
Follow-up period, Moderate (n=9)	0 0%
Follow-up period, Severe (n=9)	0 0%
Long term period 1, Absent (n=8)	100 1111.1%
Long term period 1, Minimal (n=8)	0 0%
Long term period 1, Mild (n=8)	0 0%
Long term period 1, Moderate (n=8)	0 0%
Long term period 1, Severe (n=8)	0 0%
Long term period 2, Absent (n=8)	100 1111.1%
Long term period 2, Minimal (n=8)	0 0%
Long term period 2, Mild (n=8)	0 0%
Long term period 2, Moderate (n=8)	0 0%
Long term period 2, Severe (n=8)	0 0%

10. Secondary Outcome

Title	Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment
Description	Lymphadenopathy severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.
Time Frame	Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Treatment period, Absent (n=9)	88.89 987.7%
Treatment period, Minimal (n=9)	11.11 123.4%
Treatment period, Mild (n=9)	0 0%
Treatment period, Moderate (n=9)	0 0%
Treatment period, Severe (n=9)	0 0%
Follow-up period, Absent (n=9)	77.78 864.2%
Follow-up period, Minimal (n=9)	22.22 246.9%
Follow-up period, Mild (n=9)	0 0%
Follow-up period, Moderate (n=9)	0 0%
Follow-up period, Severe (n=9)	0 0%
Long term period 1, Absent (n=8)	87.5 972.2%
Long term period 1, Minimal (n=8)	12.5 138.9%
Long term period 1, Mild (n=8)	0 0%
Long term period 1, Moderate (n=8)	0 0%
Long term period 1, Severe (n=8)	0 0%
Long term period 2, Absent (n=8)	100 1111.1%
Long term period 2, Minimal (n=8)	0 0%
Long term period 2, Mild (n=8)	0 0%
Long term period 2, Moderate (n=8)	0 0%
Long term period 2, Severe (n=8)	0 0%

11. Secondary Outcome

Title	Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment
Description	Abdominal pain was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.
Time Frame	Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Treatment period, Absent (n=9)	100 1111.1%
Treatment period, Minimal (n=9)	0 0%
Treatment period, Mild (n=9)	0 0%
Treatment period, Moderate (n=9)	0 0%
Treatment period, Severe (n=9)	0 0%
Follow-up period, Absent (n=9)	100 1111.1%
Follow-up period, Minimal (n=9)	0 0%
Follow-up period, Mild (n=9)	0 0%
Follow-up period, Moderate (n=9)	0 0%
Follow-up period, Severe (n=9)	0 0%
Long term period 1, Absent (n=8)	87.5 972.2%
Long term period 1, Minimal (n=8)	12.5 138.9%
Long term period 1, Mild (n=8)	0 0%
Long term period 1, Moderate (n=8)	0 0%
Long term period 1, Severe (n=8)	0 0%
Long term period 2, Absent (n=8)	100 1111.1%
Long term period 2, Minimal (n=8)	0 0%
Long term period 2, Mild (n=8)	0 0%
Long term period 2, Moderate (n=8)	0 0%
Long term period 2, Severe (n=8)	0 0%

12. Secondary Outcome

Title	Time to Resolution of the Initial Flare After First Canakinumab Treatment
Description	Time to resolution of the initial flare after first dose of canakinumab was determined.
Time Frame	Day 1 (Baseline), Day 28

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Median (Full Range) [Days]	3

13. Secondary Outcome

Title	Change From Baseline in Inflammation Markers Over Time up to Month 24
Description	The C-reactive Protein (CRP) and/or Serum amyloid A protein (SAA) were used as inflammatory markers. The normal range of CRP was 0-10 mg/L.
Time Frame	Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group respectively.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
CRP- 6 month (Treatment period), (n=6)	-120.5
CRP- 6 month (Follow-up period), (n=9)	-111
CRP- Long term period 1, (n=8)	-113.55
CRP- Long term period 2, (n=8)	-125.2
SAA- 6 month (Treatment period), (n=1)	-624.2
SAA- 6 month (Follow-up period), (n=2)	-685.95
SAA- Long term period 1, (n=2)	-684.1
SAA- Long term period 2, (n=2)	-686.7

14. Secondary Outcome

Title	Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time
Description	Participants were assessed for health-related quality of life (HRQoL) based on Health Assessment Questionnaire (HAQ). HAQ was an eight 8 categories questionnaire representing all activities related to physical function. Each category has various sub-categories, which were rated by the participants on a 4- point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. The total score was the mean of the 8 scores, and ranged from 0 (no disability) to 3 (completely disabled).
Time Frame	Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group respectively. Here "Number of participants analyzed" signifies the participants assessed for HAQ during study.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	6
Treatment period, (n=3)	0
Follow-up period, (n=4)	0
Long term period 1, (n=5)	0
Long term period 2, (n=4)	0

15. Secondary Outcome

Title	Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time
Description	Participants or their parents (participants aged 6 to 17 years) were assessed for HRQoL based on Childhood Health Assessment Questionnaire (CHAQ). CHAQ was an eight domain questionnaire representing functional capacity and independence, evaluated for previous week. Each domain was rated on a 4-point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do.The total score is the mean from the 8 scores, and ranges from 0 (no disability) to 3 (completely disabled).
Time Frame	Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group respectively. Here "Number of participants analyzed" signifies the participants assessed for CHAQ during study.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	6
End to treatment period (n= 2)	0
End to follow-up period (n=4)	0.1
Long term period 1, (n=2)	0.1
Long term period 2, (n=1)	0.1

16. Secondary Outcome

Title	Percentage of Participants Who Received Dose Up-titration During 6-month Treatment Period
Description	Participants who experienced a new HIDS flare between baseline and Week 4 and received an escalated dose of 450 mg of canakinumab every 6 weeks thereafter starting at Week 6 were determined.
Time Frame	Day 1 up to Month 6 (End of follow up)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Number [Percentage of participants]	22.22 246.9%

17. Secondary Outcome

Title	Duration of Flares Experienced During the Study
Description	Flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. The change in post canakinumab treatment flare duration during the study were assessed as compared to historical period.
Time Frame	Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group respectively.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Treatment period, (n=3)	3
Follow-up period, (n=7)	4
Long term period 1, (n=6)	3.5
Long term period 2, (n=2)	8.5

18. Secondary Outcome

Title	Time to Flare After the Last Dose of Canakinumab During the Follow-up Period
Description	The median time to flare by the participants after administration of the last dose of canakinumab during the follow-up period was analysed using Kaplan-Meier method.
Time Frame	Last dose of canakinumab treatment in follow-up period to end of follow-up period (Day 337)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the FAS population. Here "Number of participants analysed" signifies the participants assessed for time to flare after the last dose of canakinumab during follow-up period.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	7
Median (Full Range) [days]	110

19. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
Time Frame	Day 1 (Start of study treatment) up to Month 36 (End of study)

Outcome Measure Data

Analysis Population Description

The analysis was performed on Safety Set (SAF) population defined as all participants who received at least one application of study treatment and had at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Adverse events	9 100%
Serious adverse events	4 44.4%

20. Secondary Outcome

Title	Participants Who Received Rescue Treatment
Description	Participants who experienced flares were treated with corticosteroids and NSAIDs as rescue medication.
Time Frame	Baseline up to Month 36 (End of study)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the FAS population.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Number [Percentage of participants]	11.11 123.4%

21. Secondary Outcome

Title	Serum Concentration-time Profile of Canakinumab
Description	Canakinumab concentrations in serum were assessed for evaluating pharmacokinetics (PK) of the drug.
Time Frame	Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the FAS population.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Day 4	28.8 (7.9)
Day 15	26.9 (8)
Day 43	12.7 (4.6)
Day 85	19.4 (9.6)
Day 127	23.8 (12.8)
Day 169	24 (13.4)
Day 197	12.6 (13.7)
Day 225	11.5 (7.9)
Day 253	6.5 (4.8)
Day 281	1.6 (1.6)
Day 309	0.9 (1)
Day 337	32.6 (15.9)

22. Secondary Outcome

Title	Serum Concentration of Total Interleukin-1β Antibody (IL-1β)
Description	Pharmacodynamics of canakinumab was assessed by total IL-1β (sum of free and bound canakinumab) concentration, determined in serum by means of sandwich ELISA assay with limit of detection at 0.1 picogram/millilitre.
Time Frame	Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the FAS population.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Day 4	27.3 (25.2)
Day 15	22.2 (14.7)
Day 43	21.8 (13.9)
Day 85	27.3 (14)
Day 127	24.3 (12.1)
Day 169	32.5 (17.9)
Day 197	16.3 (5.9)
Day 225	17 (8.3)
Day 253	10.2 (5.8)
Day 281	4.9 (3.3)
Day 309	3.7 (2)
Day 337	49.1 (60.2)

23. Secondary Outcome

Title	Number of Participants Exhibiting Anti-canakinumab Antibodies at Any Visit
Description	Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using bridging ECLIA assay.
Time Frame	Baseline up to Month 36 (End of study)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the FAS population.

Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
Measure Participants	9
Number [Number of participants]	0 0%

Adverse Events

Time Frame	Serious Adverse Events are monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until LPLV.
Arm/Group Title	Canakinumab
Arm/Group Description	Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab.
All Cause Mortality
	Canakinumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Canakinumab
	Affected / at Risk (%)	# Events
Total	4/9 (44.4%)
Blood and lymphatic system disorders
Anaemia	1/9 (11.1%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/9 (11.1%)
General disorders
Disease progression	1/9 (11.1%)
Infections and infestations
Cellulitis	1/9 (11.1%)
Peritonitis	1/9 (11.1%)
Pneumonia	1/9 (11.1%)
Streptococcal bacteraemia	1/9 (11.1%)
Metabolism and nutrition disorders
Fluid overload	1/9 (11.1%)
Musculoskeletal and connective tissue disorders
Temporomandibular joint syndrome	1/9 (11.1%)
Nervous system disorders
Headache	1/9 (11.1%)
Skin and subcutaneous tissue disorders
Hidradenitis	1/9 (11.1%)
Vascular disorders
Hypertensive crisis	1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Canakinumab
	Affected / at Risk (%)	# Events
Total	9/9 (100%)
Cardiac disorders
Tachycardia	1/9 (11.1%)
Eye disorders
Conjunctival hyperaemia	1/9 (11.1%)
Conjunctivitis	1/9 (11.1%)
Gastrointestinal disorders
Abdominal pain	2/9 (22.2%)
Abdominal pain upper	1/9 (11.1%)
Aphthous stomatitis	2/9 (22.2%)
Diarrhoea	2/9 (22.2%)
Dyspepsia	2/9 (22.2%)
Toothache	1/9 (11.1%)
Vomiting	2/9 (22.2%)
General disorders
Impaired healing	1/9 (11.1%)
Influenza like illness	1/9 (11.1%)
Pyrexia	4/9 (44.4%)
Infections and infestations
Bronchitis	1/9 (11.1%)
Candidiasis	1/9 (11.1%)
Cellulitis	1/9 (11.1%)
Folliculitis	1/9 (11.1%)
Impetigo	1/9 (11.1%)
Infection	1/9 (11.1%)
Influenza	1/9 (11.1%)
Nasopharyngitis	1/9 (11.1%)
Pharyngotonsillitis	3/9 (33.3%)
Respiratory tract infection	2/9 (22.2%)
Sinusitis	1/9 (11.1%)
Tonsillitis	1/9 (11.1%)
Tonsillitis streptococcal	1/9 (11.1%)
Tooth infection	1/9 (11.1%)
Upper respiratory tract infection	1/9 (11.1%)
Urinary tract infection	2/9 (22.2%)
Vulvovaginal mycotic infection	1/9 (11.1%)
Injury, poisoning and procedural complications
Upper limb fracture	1/9 (11.1%)
Metabolism and nutrition disorders
Decreased appetite	1/9 (11.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/9 (22.2%)
Back pain	1/9 (11.1%)
Neck pain	2/9 (22.2%)
Scoliosis	1/9 (11.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bone neoplasm	1/9 (11.1%)
Nervous system disorders
Dizziness	1/9 (11.1%)
Headache	1/9 (11.1%)
Reproductive system and breast disorders
Vaginal ulceration	1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Cough	1/9 (11.1%)
Oropharyngeal pain	1/9 (11.1%)
Skin and subcutaneous tissue disorders
Alopecia	1/9 (11.1%)
Eczema	1/9 (11.1%)
Erythema nodosum	1/9 (11.1%)
Hidradenitis	1/9 (11.1%)
Surgical and medical procedures
Tooth extraction	1/9 (11.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (i.e, data from all sites) in the clinical trial.