Mevalonate Kinase Deficiency
Conditions
Keywords
Hyper IgD syndrome, canakinumab, HIDS, mevalonate kinase deficiency, MKD
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.
Interventions
DRUGCanakinumab
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
24 Months to No maximum
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Spain
Participant flow
Recruitment details
The study was conducted at 3 centres in Spain.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Canakinumab 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. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of compliance to study procedures | 1 |
Baseline characteristics
| Characteristic | Canakinumab |
|---|---|
| Age, Continuous | 17.3 years |
| Age, Customized Adolescents (12--17 years) | 3 participants |
| Age, Customized Adults (18--64 years) | 3 participants |
| Age, Customized Children (2--11 years) | 3 participants |
| Region of Enrollment Spain | 9 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 4 / 9 |
Outcome results
Primary
Number of Flares Per Participant During Historical Period and 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.
Time frame: Historical period, Month 6 (End of treatment period)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Canakinumab | Number of Flares Per Participant During Historical Period and Treatment Period | Historical period | 5 Number of flares |
| Canakinumab | Number of Flares Per Participant During Historical Period and Treatment Period | Month 6 | 0 Number of flares |
Secondary
Change From Baseline in Inflammation Markers Over Time up to Month 24
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Canakinumab | Change From Baseline in Inflammation Markers Over Time up to Month 24 | CRP- 6 month (Treatment period), (n=6) | -120.5 milligram(s)/liter |
| Canakinumab | Change From Baseline in Inflammation Markers Over Time up to Month 24 | CRP- 6 month (Follow-up period), (n=9) | -111 milligram(s)/liter |
| Canakinumab | Change From Baseline in Inflammation Markers Over Time up to Month 24 | CRP- Long term period 1, (n=8) | -113.55 milligram(s)/liter |
| Canakinumab | Change From Baseline in Inflammation Markers Over Time up to Month 24 | CRP- Long term period 2, (n=8) | -125.2 milligram(s)/liter |
| Canakinumab | Change From Baseline in Inflammation Markers Over Time up to Month 24 | SAA- 6 month (Treatment period), (n=1) | -624.2 milligram(s)/liter |
| Canakinumab | Change From Baseline in Inflammation Markers Over Time up to Month 24 | SAA- 6 month (Follow-up period), (n=2) | -685.95 milligram(s)/liter |
| Canakinumab | Change From Baseline in Inflammation Markers Over Time up to Month 24 | SAA- Long term period 1, (n=2) | -684.1 milligram(s)/liter |
| Canakinumab | Change From Baseline in Inflammation Markers Over Time up to Month 24 | SAA- Long term period 2, (n=2) | -686.7 milligram(s)/liter |
Secondary
Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Canakinumab | Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time | End to treatment period (n= 2) | 0 Score on a scale |
| Canakinumab | Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time | End to follow-up period (n=4) | 0.1 Score on a scale |
| Canakinumab | Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time | Long term period 1, (n=2) | 0.1 Score on a scale |
| Canakinumab | Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time | Long term period 2, (n=1) | 0.1 Score on a scale |
Secondary
Duration of Flares Experienced During the Study
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Canakinumab | Duration of Flares Experienced During the Study | Treatment period, (n=3) | 3 Days |
| Canakinumab | Duration of Flares Experienced During the Study | Follow-up period, (n=7) | 4 Days |
| Canakinumab | Duration of Flares Experienced During the Study | Long term period 1, (n=6) | 3.5 Days |
| Canakinumab | Duration of Flares Experienced During the Study | Long term period 2, (n=2) | 8.5 Days |
Secondary
Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Canakinumab | Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time | Treatment period, (n=3) | 0 Score on a scale |
| Canakinumab | Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time | Follow-up period, (n=4) | 0 Score on a scale |
| Canakinumab | Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time | Long term period 1, (n=5) | 0 Score on a scale |
| Canakinumab | Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time | Long term period 2, (n=4) | 0 Score on a scale |
Secondary
Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period
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)
Population: The analysis was performed in the FAS population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Canakinumab | Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period | Treatment period | 0 Number of flares |
| Canakinumab | Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period | Long term treatment period | 0 Number of flares |
Secondary
Number of Participants Exhibiting Anti-canakinumab Antibodies at Any Visit
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)
Population: The analysis was performed on the FAS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab | Number of Participants Exhibiting Anti-canakinumab Antibodies at Any Visit | 0 Number of participants |
Secondary
Number of Participants Who Flared at Month 6, Month 24 and Month 36
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)
Population: The analysis was performed in the FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Number of Participants Who Flared at Month 6, Month 24 and Month 36 | Treatment period | 2 Number of participants |
| Canakinumab | Number of Participants Who Flared at Month 6, Month 24 and Month 36 | End of Long term treatment Period 1 | 4 Number of participants |
| Canakinumab | Number of Participants Who Flared at Month 6, Month 24 and Month 36 | End of Long term treatment Period 2 | 2 Number of participants |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events | 9 Number of participants |
| Canakinumab | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious adverse events | 4 Number of participants |
Secondary
Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score
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)
Population: The analysis was performed in the FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Treatment period, Absent | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Treatment period, Minimal | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Treatment period, Mild | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Treatment period, Moderate | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Treatment period, Severe | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Follow-up period, Absent | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Follow-up period, Minimal | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Follow-up period, Mild | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Follow-up period, Moderate | 2 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Follow-up period, Severe | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Long term period 1, Absent | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Long term period 1, Minimal | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Long term period 1, Mild | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Long term period 1, Moderate | 2 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Long term period 1, Severe | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Long term period 2, Absent | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Long term period 2, Minimal | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Long term period 2, Mild | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Long term period 2, Moderate | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Long term period 2, Severe | 0 Number of participants |
Secondary
Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score
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)]
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Day 45, Absent (n=9) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Day 45, Minimal (n=9) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Day 45,Mild (n=9) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Day 45,Moderate (n=9) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Day 45,Severe (n=9) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 1, Absent (n=2) | 2 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 1, Minimal (n=2) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 1, Mild (n=2) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 1, Moderated (n=2) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 1, Severe (n=2) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 2, Absent (n=2) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 2, Minimal (n=2) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 2, Mild (n=2) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 2, Moderate (n=2) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 2, Severe (n=2) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 3, Absent (n=2) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 3, Minimal (n=2) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 3, Mild (n=2) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 3, Moderate (n=2) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Flare/Unscheduled visit 3, Severe (n=2) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | End of Treatment period, Absent (n=7) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | End of Treatment period, Minimal (n=7) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | End of Treatment period, Mild (n=7) | 4 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | End of Treatment period, Moderate (n=7) | 3 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | End of Treatment period, Severe (n=7) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | End of Follow-up period, Absent (n=8) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | End of Follow-up period, Minimal (n=8) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | End of Follow-up period, Mild (n=8) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | End of Follow-up period, Moderate (n=8) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | End of Follow-up period, Severe (n=8) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 1, Flare 1, Absent (n=3) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 1, Flare 1, Minimal (n=3) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 1, Flare 1, Mild (n=3) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long-term 12 M period, Flare 1, Moderate (n=3) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long-term 12 M period, Flare 1, Severe (n=3) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 1, Flare 2, Absent (n=1) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long-term 12 M period, Flare 2, Minimal (n=1) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long-term 12 M period, Flare 2, Mild (n=1) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 1, Flare 2, Moderate (n=1) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 1, Flare 2, Severe (n=1) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 1, Flare 3, Absent (n=1) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 1, Flare 3, Minimal (n=1) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 1, Flare 3, Mild (n=1) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 1, Flare 3, Moderate (n=1) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 1, Flare 3, Severe (n=1) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 2, Absent (n=2) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 2, Minimal (n=2) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 2, Mild (n=2) | 1 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 2, Moderate (n=2) | 0 Number of participants |
| Canakinumab | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Long term period 2, Severe (n=2) | 0 Number of participants |
Secondary
Participants Who Received Rescue Treatment
Participants who experienced flares were treated with corticosteroids and NSAIDs as rescue medication.
Time frame: Baseline up to Month 36 (End of study)
Population: The analysis was performed on the FAS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab | Participants Who Received Rescue Treatment | 11.11 Percentage of participants |
Secondary
Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Treatment period, Absent (n=9) | 100 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Treatment period, Minimal (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Treatment period, Mild (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Treatment period, Moderate (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Treatment period, Severe (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Follow-up period, Absent (n=9) | 100 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Follow-up period, Minimal (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Follow-up period, Mild (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Follow-up period, Moderate (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Follow-up period, Severe (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Long term period 1, Absent (n=8) | 87.5 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Long term period 1, Minimal (n=8) | 12.5 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Long term period 1, Mild (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Long term period 1, Moderate (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Long term period 1, Severe (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Long term period 2, Absent (n=8) | 100 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Long term period 2, Minimal (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Long term period 2, Mild (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Long term period 2, Moderate (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Long term period 2, Severe (n=8) | 0 Percentage of participants |
Secondary
Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Treatment period, Absent (n=9) | 88.89 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Treatment period, Minimal (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Treatment period, Mild (n=9) | 11.11 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Treatment period, Moderate (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Treatment period, Severe (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Follow-up period, Absent (n=9) | 100 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Follow-up period, Minimal (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Follow-up period, Mild (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Follow-up period, Moderate (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Follow-up period, Severe (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Long term period 1, Absent (n=8) | 100 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Long term period 1, Minimal (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Long term period 1, Mild (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Long term period 1, Moderate (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Long term period 1, Severe (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Long term period 2, Absent (n=8) | 100 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Long term period 2, Minimal (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Long term period 2, Mild (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Long term period 2, Moderate (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Long term period 2, Severe (n=8) | 0 Percentage of participants |
Secondary
Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Treatment period, Absent (n=9) | 88.89 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Treatment period, Minimal (n=9) | 11.11 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Treatment period, Mild (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Treatment period, Moderate (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Treatment period, Severe (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Follow-up period, Absent (n=9) | 100 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Follow-up period, Minimal (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Follow-up period, Mild (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Follow-up period, Moderate (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Follow-up period, Severe (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Long term period 1, Absent (n=8) | 75 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Long term period 1, Minimal (n=8) | 12.5 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Long term period 1, Mild (n=8) | 12.5 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Long term period 1, Moderate (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Long term period 1, Severe (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Long term period 2, Absent (n=8) | 100 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Long term period 2, Minimal (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Long term period 2, Mild (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Long term period 2, Moderate (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Long term period 2, Severe (n=8) | 0 Percentage of participants |
Secondary
Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Treatment period, Absent (n=9) | 88.89 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Treatment period, Minimal (n=9) | 11.11 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Treatment period, Mild (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Treatment period, Moderate (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Treatment period, Severe (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Follow-up period, Absent (n=9) | 77.78 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Follow-up period, Minimal (n=9) | 22.22 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Follow-up period, Mild (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Follow-up period, Moderate (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Follow-up period, Severe (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Long term period 1, Absent (n=8) | 87.5 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Long term period 1, Minimal (n=8) | 12.5 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Long term period 1, Mild (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Long term period 1, Moderate (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Long term period 1, Severe (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Long term period 2, Absent (n=8) | 100 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Long term period 2, Minimal (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Long term period 2, Mild (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Long term period 2, Moderate (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Long term period 2, Severe (n=8) | 0 Percentage of participants |
Secondary
Percentage of Participants Who Received Dose Up-titration During 6-month Treatment Period
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)
Population: The analysis was performed in the FAS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab | Percentage of Participants Who Received Dose Up-titration During 6-month Treatment Period | 22.22 Percentage of participants |
Secondary
Percentage of Participants With Defined Grades of Participants Assessed Symptom Control
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Treatment period, No control (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Treatment period, Poor control (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Treatment period, Somewhat control (n=9) | 11.11 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Treatment period, Good control (n=9) | 33.33 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Treatment period, Excellent control (n=9) | 55.56 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Follow-up period, No control (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Follow-up period, Poor control (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Follow-up period, Somewhat control (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Follow-up period, Good control (n=9) | 33.33 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Follow-up period, Excellent control (n=9) | 66.67 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Long term period 1, No control (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Long term period 1, Poor control (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Long term period 1, Somewhat control (n=8) | 12.5 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Long term period 1, Good control (n=8) | 25 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Long term period 1, Excellent control (n=8) | 62.5 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Long term period 2, No control (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Long term period 2, Poor control (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Long term period 2, Somewhat control (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Long term period 2, Good control (n=8) | 12.5 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Long term period 2, Excellent control (n=8 | 87.5 Percentage of participants |
Secondary
Percentage of Participants With Defined Grades of Physician Assessed Symptom Control
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Treatment period, No control (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Treatment period, Poor control (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Treatment period, Somewhat control (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Treatment period, Good control (n=9) | 44.44 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Treatment period, Excellent control (n=9) | 55.56 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Follow-up period, No control (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Follow-up period, Poor control (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Follow-up period, Somewhat control (n=9) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Follow-up period, Good control (n=9) | 33.33 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Follow-up period, Excellent control (n=9) | 66.67 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Long term period 1, No control (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Long term period 1, Poor control (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Long term period 1, Somewhat control (n=8) | 12.5 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Long term period 1, Good control (n=8) | 25 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Long term period 1, Excellent control (n=8) | 62.5 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Long term period 2, No control (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Long term period 2, Poor control (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Long term period 2, Somewhat control (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Long term period 2, Good control (n=8) | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Long term period 2, Excellent control (n=8 | 100 Percentage of participants |
Secondary
Serum Concentration of Total Interleukin-1β Antibody (IL-1β)
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)
Population: The analysis was performed on the FAS population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 4 | 27.3 picogram(s)/milliliter | Standard Deviation 25.2 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 15 | 22.2 picogram(s)/milliliter | Standard Deviation 14.7 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 43 | 21.8 picogram(s)/milliliter | Standard Deviation 13.9 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 85 | 27.3 picogram(s)/milliliter | Standard Deviation 14 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 127 | 24.3 picogram(s)/milliliter | Standard Deviation 12.1 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 169 | 32.5 picogram(s)/milliliter | Standard Deviation 17.9 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 197 | 16.3 picogram(s)/milliliter | Standard Deviation 5.9 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 225 | 17 picogram(s)/milliliter | Standard Deviation 8.3 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 253 | 10.2 picogram(s)/milliliter | Standard Deviation 5.8 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 281 | 4.9 picogram(s)/milliliter | Standard Deviation 3.3 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 309 | 3.7 picogram(s)/milliliter | Standard Deviation 2 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 337 | 49.1 picogram(s)/milliliter | Standard Deviation 60.2 |
Secondary
Serum Concentration-time Profile of Canakinumab
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)
Population: The analysis was performed on the FAS population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 4 | 28.8 microgram(s)/milliliter | Standard Deviation 7.9 |
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 15 | 26.9 microgram(s)/milliliter | Standard Deviation 8 |
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 43 | 12.7 microgram(s)/milliliter | Standard Deviation 4.6 |
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 85 | 19.4 microgram(s)/milliliter | Standard Deviation 9.6 |
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 127 | 23.8 microgram(s)/milliliter | Standard Deviation 12.8 |
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 169 | 24 microgram(s)/milliliter | Standard Deviation 13.4 |
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 197 | 12.6 microgram(s)/milliliter | Standard Deviation 13.7 |
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 225 | 11.5 microgram(s)/milliliter | Standard Deviation 7.9 |
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 253 | 6.5 microgram(s)/milliliter | Standard Deviation 4.8 |
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 281 | 1.6 microgram(s)/milliliter | Standard Deviation 1.6 |
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 309 | 0.9 microgram(s)/milliliter | Standard Deviation 1 |
| Canakinumab | Serum Concentration-time Profile of Canakinumab | Day 337 | 32.6 microgram(s)/milliliter | Standard Deviation 15.9 |
Secondary
Time to Flare After the Last Dose of Canakinumab During the Follow-up Period
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab | Time to Flare After the Last Dose of Canakinumab During the Follow-up Period | 110 days |
Secondary
Time to Resolution of the Initial Flare After First Canakinumab Treatment
Time to resolution of the initial flare after first dose of canakinumab was determined.
Time frame: Day 1 (Baseline), Day 28
Population: The analysis was performed in the FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab | Time to Resolution of the Initial Flare After First Canakinumab Treatment | 3 Days |