Juvenile Idiopathic Arthritis
Conditions
Brief summary
Primary Objective: To describe the pharmacokinetic (PK) profile of sarilumab in participants aged 2-17 years with Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) in order to identify the dose and regimen for adequate treatment of this population Secondary Objective: To describe the pharmacodynamic (PD) profile, the efficacy and the long-term safety of sarilumab in participants with pcJIA.
Detailed description
For 73 participants enrolled in the dose-finding and second portions, the total study duration per participant was up to 166 weeks that consists of a 4- week screening, a 12-week core treatment phase, a 144-week extension phase, and a 6-week post-treatment follow-up. For 29 participants enrolled in the third portion, the total study duration per participant was up to 106 weeks that consists of a 4- week screening, a 12-week core treatment phase, a 84-week extension phase, and a 6-week post-treatment follow-up.
Interventions
DRUGSarilumab
Pharmaceutical form:Solution Route of administration: Subcutaneous
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
: * Male and female participants aged ≥2 and ≤17 years (or country specified age requirement) at the time of the screening visit. * Diagnosis of rheumatoid factor-negative or rheumatoid factor positive polyarticular Juvenile Idiopathic Arthritis (JIA) subtype or oligoarticular extended JIA subtype according to the International League of Associations for Rheumatology (ILAR) 2001 Juvenile Idiopathic Arthritis Classification Criteria with at least 5 active joints as per American College of Rheumatology (ACR) definition for active arthritis at Screening * Participant with an inadequate response to current treatment and considered as a candidate for a biologic disease modifying antirheumatic drug (DMARD) as per investigator's judgment
Exclusion criteria
* Body weight \<10 kg or \>60 kg for participants enrolled in the 3 ascending dose cohorts, then body weight \<10 kg for participants subsequently enrolled at the selected dose-regimen. * If nonsteroidal anti-inflammatory drugs (NSAIDs) \[including cyclo oxygenase-2 inhibitors (COX-2)\] taken, dose stable for \<2 weeks prior to the baseline visit and/or dosing prescribed outside of approved label. * If non-biologic DMARD taken, dose stable for \<6 weeks prior to the baseline visit or at a dose exceeding the recommended dose as per local labeling. * If oral glucocorticoid taken, dose exceeding equivalent prednisone dose 0.5 mg/kg/day (or 30 mg/day) within 2 weeks prior to baseline. * Use of parenteral or intra-articular glucocorticoid injection within 4 weeks prior to baseline. * Prior treatment with anti-interleukin 6 (IL-6) or IL-6 receptor (IL-6R) antagonist therapies, including but not limited to tocilizumab or sarilumab. * Treatment with any biologic treatment for pcJIA within 5 half-lives prior to the first dose of sarilumab. * Treatment with a Janus kinase inhibitor within 4 weeks prior to the first dose of sarilumab; and treatment with growth hormone within 4 weeks prior to the first dose of sarilumab (the required off treatment periods and procedures may vary according to local requirements). * Treatment with any investigational biologic or non-biologic product within 8 weeks or 5 half-lives prior to baseline, whichever is longer. * Lipid lowering drug stable for less than 6 weeks prior to screening. * Exclusion related to tuberculosis (TB). *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Sarilumab at Week 12 | Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12 | The Cmax was defined as maximum serum concentration. The values reported are mean and standard deviation. |
| Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12 | Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12 | The AUC0-t was defined as area under the concentration in serum versus time curve calculated using the trapezoidal method during a dose interval (tau). The values reported are mean and standard deviation. |
| Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12 | Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12 | The Ctrough was defined as concentration observed before treatment administration during repeated dosing from baseline to Week 12. The values reported are mean and standard deviation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12 | Baseline (Day 1) and Week 12 | Serum concentrations of sIL-6R was determined to assess the PD effects of sarilumab. The values reported are mean and standard deviation. |
| Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology (JIA ACR) 30 Response at Week 12 | Week 12 | JIA ACR30 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 30% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%. |
| Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156 | Weeks 12, 24, 48, 96, and 156 | JIA ACR30 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 30% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%. |
| Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Week 12 | Week 12 | JIA ACR50 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 50% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%. |
| Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156 | Weeks 12, 24, 48, 96, and 156 | JIA ACR50 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 50% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%. |
| Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Week 12 | Week 12 | JIA ACR70 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 70% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%. |
| Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156 | Weeks 12, 24, 48, 96, and 156 | JIA ACR70 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 70% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%. |
| Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Week 12 | Week 12 | JIA ACR90 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 90% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%. |
| Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156 | Weeks 12, 24, 48, 96, and 156 | JIA ACR90 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 90% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%. |
| Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Week 12 | Week 12 | JIA ACR100 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 100% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%. |
| Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156 | Weeks 12, 24, 48, 96, and 156 | JIA ACR100 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 100% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%. |
| Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Week 12 | Baseline (Day 1) and Week 12 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using visual analog scale (VAS), Childhood Health Questionnaire Disability Index (CHAQ-DI) and hs-CRP. Activity joint count-71 was calculated as sum (joints with active arthritis)\*(71/number of joints with assessment). |
| Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156 | Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Activity joint count-71 was calculated as sum (joints with active arthritis)\*(71/number of joints with assessment). |
| Cohorts 1 and 3: Change From Baseline in High-Sensitivity C-reactive Protein (Hs-CRP) at Week 12 | Baseline (Day 1) and Week 12 | Serum concentrations of hs-CRP was determined to assess the Pharmacodynamic (PD) effects of sarilumab. The values reported are mean and standard deviation. |
| Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156 | Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Limited motion joint count was calculated as sum (joints with limited motion)\*(67/number of joints with assessment). |
| Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Week 12 | Baseline (Day 1) and Week 12 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. The CHAQ questionnaire consists of 30 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain is scored on a 4 point scale ranges from 0 to 3: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). An additional response of not applicable is available to indicate activities the participant is unable to perform because he/she is too young. The CHAQ-DI total score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst). Higher scores indicate worse outcome. |
| Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156 | Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. The CHAQ questionnaire consists of 30 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain is scored on a 4 point scale ranges from 0 to 3: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). An additional response of not applicable is available to indicate activities the participant is unable to perform because he/she is too young. The CHAQ-DI total score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst). Higher scores indicate worse outcome. |
| Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Week 12 | Baseline (Day 1) and Week 12 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Serum concentrations of hs-CRP was determined to assess the PD effects of sarilumab. |
| Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156 | Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Serum concentrations of hs-CRP was determined to assess the PD effects of sarilumab. |
| Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Week 12 | Baseline (Day 1) and Week 12 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Physician global assessment of disease activity was assessed on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome. |
| Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156 | Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Physician global assessment of disease activity was assessed on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome. |
| Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Week 12 | Baseline (Day 1) and Week 12 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Participant/parent assessment of overall well-being was rated on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome. |
| Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156 | Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Participant/parent assessment of overall well-being was rated on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome. |
| Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | Baseline (Day 1) and Week 12 | The JADAS is used for assessment of disease activity, and it includes 4 measures: Physician global assessment of disease activity (VAS range: 0 to10; where 0= no activity and 10= maximum activity), parent/participant global assessment of well-being (VAS range: 0 to 10; where 0= no activity and10= maximum activity), count of joints with active disease (range: 0 to 27; where 0= no activity and 27= maximum activity), and index of inflammation determined by hs-CRP or ESR (normalized scale range: 0 to 10; where 0= no disease activity and 10= maximum disease activity). The JADAS total score is calculated as the simple sum of the scores of its 4 components. The total score ranges from 0 to 57 where 0= no disease activity and 57= maximum disease activity. Higher scores indicate higher disease activity. Clinical JADAS-27 is without CRP or ESR component and score ranges from 0 to 47 where 0= no disease activity and 47= maximum disease activity. |
| Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156 | The JADAS is used for assessment of disease activity, and it includes 4 measures: Physician global assessment of disease activity (VAS range: 0 to10; where 0= no activity and 10= maximum activity), parent/participant global assessment of well-being (VAS range: 0 to 10; where 0= no activity and10= maximum activity), count of joints with active disease (range: 0 to 27; where 0= no activity and 27= maximum activity), and index of inflammation determined by hs-CRP or ESR (normalized scale range: 0 to 10; where 0= no disease activity and 10= maximum disease activity). The JADAS total score is calculated as the simple sum of the scores of its 4 components. The total score ranges from 0 to 57 where 0= no disease activity and 57= maximum disease activity. Higher scores indicate higher disease activity. Clinical JADAS-27 is without CRP or ESR component and score ranges from 0 to 47 where 0= no disease activity and 47= maximum disease activity. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | From the first administration of study treatment (Day 1) up to end of treatment period, maximum of 156 weeks for portions 1 and 2 and 96 weeks for portion 3 | An adverse events (AEs) is any untoward medical occurrence in a participant or in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with the study treatment. An SAE is any untoward medical occurrence that at any dose results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect or is an important medical event. TEAEs are defined as AEs that develop or worsen during the on-treatment period \[that is, from the time of first dose of study treatment up to 6 weeks after the last administration of the study treatment\]. |
| Number of Participants With Local Site Reactions | From the first administration of study treatment (Day 1) up to end of treatment period, maximum of 156 weeks for portions 1 and 2 and 96 weeks for portion 3 | Participants were observed for at least 30 minutes after each study treatment administration either on site or at home and any local reactions were noted in the diary regardless of being clinically significant. |
| Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Week 12 | Baseline (Day 1) and Week 12 | The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Limited motion joint count was calculated as sum (joints with limited motion)\*(67/number of joints with assessment). |
| Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156 | Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156 | Serum concentrations of hs-CRP was determined to assess the PD effects of sarilumab. The values reported are mean and standard deviation. |
| Change From Baseline in Interleukin-6 (IL-6) at Week 12 | Baseline (Day 1) and Week 12 | Serum concentrations of IL-6 was determined to assess the PD effects of sarilumab. The values reported are mean and standard deviation. |
Countries
Argentina, Canada, Chile, Czechia, Finland, France, Germany, Italy, Mexico, Netherlands, Poland, Russia, Spain, United Kingdom, United States
Participant flow
Recruitment details
Group A: \>=30kg and \<=60kg and Group B: \<30kg and \>=10kg. Portion 1 of study enrolled participants into 3 dosing regimens (Cohort 1, 2 and 3). Cohort 1: dose capped at 150mg q2w (Group A:2mg/kg q2w; Group B:2.5mg/kg q2w). Cohort 2: dose capped at 200mg q2w (Group A:3mg/kg q2w; Group B:4mg/kg q2w). Cohort 3: dose capped at 150mg qw (Group A:2mg/kg qw; Group B:2.5mg/kg qw). All 3 cohorts in Portion 1 received 12-week core treatment phase and eligible participants entered 144-week extension phase.
Pre-assignment details
After dose-finding portion, 200mg q2w dose was selected for continuation in study. Portion 1 participants from Cohorts 1 and 3 who continued into extension phase switched to this dose after dose was selected. Participants enrolled into Portions 2 and 3 started on selected dose of 200mg q2w capped dose (Group A: 3 mg/kg q2w; Group B: 4 mg/kg q2w) for extension phase (144 weeks for Portion 2 and 84 weeks for Portion 3). A total of 102 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: >= 30 kg and <= 60 kg Participants with body weight \>= 30 kg and \<= 60 kg received sarilumab 2 mg/kg SC injection q2w for 12 weeks in core treatment phase. Eligible participants continued to receive 2 mg/kg SC injection q2w until the selected dose was found and then switched to selected dose of 3 mg/kg SC injection q2w in extension phase (portion 1: up to 144 weeks in extension phase). | 7 |
| Cohort 1: < 30 kg and >= 10 kg Participants with body weight \< 30 kg and \>= 10 kg received sarilumab 2.5 mg/kg SC injection q2w for 12 weeks in core treatment phase. Eligible participants continued to receive 2.5 mg/kg SC injection q2w until the selected dose was found and then switched to selected dose of 4 mg/kg SC injection q2w in extension phase (portion 1: up to 144 weeks in extension phase). | 6 |
| Cohort 2: >= 30 kg and <= 60 kg Participants with body weight \>= 30 kg and \<= 60 kg received sarilumab 3 mg/kg SC injection q2w for 12 weeks in core treatment phase. Eligible participants continued to receive 3 mg/kg SC injection q2w in extension phase (portions 1 and 2: up to 144 weeks in extension phase and portion 3: up to 84 weeks in extension phase). | 42 |
| Cohort 2: < 30 kg and >= 10 kg Participants with body weight \< 30 kg and \>= 10 kg received sarilumab 4 mg/kg SC injection q2w for 12 weeks in core treatment phase. Eligible participants continued to receive 4 mg/kg SC injection q2w in extension phase (portions 1 and 2: up to 144 weeks in extension phase and portion 3: up to 84 weeks in extension phase). | 31 |
| Cohort 3: >= 30 kg and <= 60 kg Participants with body weight \>= 30 kg and \<= 60 kg received sarilumab 2 mg/kg SC injection qw for 12 weeks in core treatment phase. Eligible participants continued to receive 2 mg/kg SC injection qw until the selected dose was found and then switched to selected dose of 3 mg/kg SC injection qw in extension phase (portion 1: up to 144 weeks in extension phase). | 6 |
| Cohort 3: < 30 kg and >= 10 kg Participants with body weight \< 30 kg and \>= 10 kg received sarilumab 2.5 mg/kg SC injection qw for 12 weeks in core treatment phase. Eligible participants continued to receive 2.5 mg/kg SC injection qw until the selected dose was found and then switched to selected dose of 4 mg/kg SC injection qw in extension phase (portion 1: up to 144 weeks in extension phase). | 9 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 3 | 0 | 0 | 0 |
| Overall Study | Withdrawal by parent/guardian | 0 | 0 | 2 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: >= 30 kg and <= 60 kg | Cohort 1: < 30 kg and >= 10 kg | Cohort 2: >= 30 kg and <= 60 kg | Cohort 2: < 30 kg and >= 10 kg | Cohort 3: >= 30 kg and <= 60 kg | Cohort 3: < 30 kg and >= 10 kg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 12.3 years STANDARD_DEVIATION 3.3 | 6.5 years STANDARD_DEVIATION 3.2 | 12.6 years STANDARD_DEVIATION 3 | 5.4 years STANDARD_DEVIATION 3.1 | 13.7 years STANDARD_DEVIATION 3 | 4.8 years STANDARD_DEVIATION 2.4 | 9.4 years STANDARD_DEVIATION 4.7 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 3 Participants | 39 Participants | 28 Participants | 4 Participants | 8 Participants | 88 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 35 Participants | 23 Participants | 3 Participants | 6 Participants | 77 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 7 Participants | 8 Participants | 3 Participants | 3 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 42 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 31 | 0 / 5 | 0 / 5 | 0 / 9 |
| other Total, other adverse events | 7 / 7 | 39 / 42 | 4 / 4 | 5 / 6 | 5 / 6 | 6 / 6 | 29 / 31 | 5 / 5 | 5 / 5 | 9 / 9 |
| serious Total, serious adverse events | 2 / 7 | 3 / 42 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 3 / 31 | 0 / 5 | 0 / 5 | 0 / 9 |
Outcome results
Primary
Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12
The AUC0-t was defined as area under the concentration in serum versus time curve calculated using the trapezoidal method during a dose interval (tau). The values reported are mean and standard deviation.
Time frame: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12
Population: The PK analysis set included all participants in the safety population with at least 1 post-dose, non-missing serum concentration value. Only participants with data collected are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12 | 61.4 day*mg/L | Standard Deviation 25.2 |
| Cohort 1: < 30 kg and >= 10 kg | Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12 | 106 day*mg/L | Standard Deviation 36.8 |
| Cohort 2: >= 30 kg and <= 60 kg | Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12 | 212 day*mg/L | Standard Deviation 77.2 |
| Cohort 2: < 30 kg and >= 10 kg | Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12 | 318 day*mg/L | Standard Deviation 90 |
| Cohort 3: >= 30 kg and <= 60 kg | Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12 | 202 day*mg/L | Standard Deviation 55 |
| Cohort 3: < 30 kg and >= 10 kg | Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12 | 192 day*mg/L | Standard Deviation 60.7 |
Primary
Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12
The Ctrough was defined as concentration observed before treatment administration during repeated dosing from baseline to Week 12. The values reported are mean and standard deviation.
Time frame: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12
Population: The PK analysis set included all participants in the safety population with at least 1 post-dose, non-missing serum concentration value. Only participants with data collected are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12 | 1.30 mg/L | Standard Deviation 0.952 |
| Cohort 1: < 30 kg and >= 10 kg | Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12 | 1.32 mg/L | Standard Deviation 1.27 |
| Cohort 2: >= 30 kg and <= 60 kg | Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12 | 5.76 mg/L | Standard Deviation 3.57 |
| Cohort 2: < 30 kg and >= 10 kg | Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12 | 9.88 mg/L | Standard Deviation 5.42 |
| Cohort 3: >= 30 kg and <= 60 kg | Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12 | 22.2 mg/L | Standard Deviation 7.12 |
| Cohort 3: < 30 kg and >= 10 kg | Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12 | 23.2 mg/L | Standard Deviation 8.28 |
Primary
Maximum Serum Concentration (Cmax) of Sarilumab at Week 12
The Cmax was defined as maximum serum concentration. The values reported are mean and standard deviation.
Time frame: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12
Population: The Pharmacokinetic (PK) analysis set included all participants in the safety population with at least 1 post-dose, non-missing serum concentration value. Only participants with data collected are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Maximum Serum Concentration (Cmax) of Sarilumab at Week 12 | 7.57 milligram per liter (mg/L) | Standard Deviation 4.14 |
| Cohort 1: < 30 kg and >= 10 kg | Maximum Serum Concentration (Cmax) of Sarilumab at Week 12 | 13.7 milligram per liter (mg/L) | Standard Deviation 2.52 |
| Cohort 2: >= 30 kg and <= 60 kg | Maximum Serum Concentration (Cmax) of Sarilumab at Week 12 | 22.0 milligram per liter (mg/L) | Standard Deviation 8.07 |
| Cohort 2: < 30 kg and >= 10 kg | Maximum Serum Concentration (Cmax) of Sarilumab at Week 12 | 33.6 milligram per liter (mg/L) | Standard Deviation 7.16 |
| Cohort 3: >= 30 kg and <= 60 kg | Maximum Serum Concentration (Cmax) of Sarilumab at Week 12 | 32.0 milligram per liter (mg/L) | Standard Deviation 7.27 |
| Cohort 3: < 30 kg and >= 10 kg | Maximum Serum Concentration (Cmax) of Sarilumab at Week 12 | 31.0 milligram per liter (mg/L) | Standard Deviation 7.98 |
Secondary
Change From Baseline in Interleukin-6 (IL-6) at Week 12
Serum concentrations of IL-6 was determined to assess the PD effects of sarilumab. The values reported are mean and standard deviation.
Time frame: Baseline (Day 1) and Week 12
Population: All treated population included participants who signed informed consent and received at least 1 dose of the study treatment. Only participants with data collected at Baseline and Week 12 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Change From Baseline in Interleukin-6 (IL-6) at Week 12 | 1.27 nanogram (ng)/L | Standard Deviation 9.79 |
| Cohort 1: < 30 kg and >= 10 kg | Change From Baseline in Interleukin-6 (IL-6) at Week 12 | 13.65 nanogram (ng)/L | Standard Deviation 18.2 |
| Cohort 2: >= 30 kg and <= 60 kg | Change From Baseline in Interleukin-6 (IL-6) at Week 12 | 43.71 nanogram (ng)/L | Standard Deviation 113.42 |
| Cohort 2: < 30 kg and >= 10 kg | Change From Baseline in Interleukin-6 (IL-6) at Week 12 | 11.36 nanogram (ng)/L | Standard Deviation 35.81 |
| Cohort 3: >= 30 kg and <= 60 kg | Change From Baseline in Interleukin-6 (IL-6) at Week 12 | 66.21 nanogram (ng)/L | Standard Deviation 86.21 |
| Cohort 3: < 30 kg and >= 10 kg | Change From Baseline in Interleukin-6 (IL-6) at Week 12 | 9.20 nanogram (ng)/L | Standard Deviation 26.5 |
Secondary
Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12
Serum concentrations of sIL-6R was determined to assess the PD effects of sarilumab. The values reported are mean and standard deviation.
Time frame: Baseline (Day 1) and Week 12
Population: All treated population included participants who signed informed consent and received at least 1 dose of the study treatment. Only participants with data collected at Baseline and Week 12 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12 | 40.09 ng/mL | Standard Deviation 49.75 |
| Cohort 1: < 30 kg and >= 10 kg | Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12 | 101.50 ng/mL | Standard Deviation 129.59 |
| Cohort 2: >= 30 kg and <= 60 kg | Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12 | 316.77 ng/mL | Standard Deviation 129.29 |
| Cohort 2: < 30 kg and >= 10 kg | Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12 | 388.33 ng/mL | Standard Deviation 185.82 |
| Cohort 3: >= 30 kg and <= 60 kg | Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12 | 535.76 ng/mL | Standard Deviation 98.12 |
| Cohort 3: < 30 kg and >= 10 kg | Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12 | 582.95 ng/mL | Standard Deviation 149.52 |
Secondary
Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156
Serum concentrations of hs-CRP was determined to assess the PD effects of sarilumab. The values reported are mean and standard deviation.
Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
Population: All treated population included participants who signed informed consent and received at least 1 dose of the study treatment. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156 | Week 24 | -8.54 mg/L | Standard Deviation 19.17 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156 | Week 96 | -9.39 mg/L | Standard Deviation 21.65 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156 | Week 48 | -9.93 mg/L | Standard Deviation 21.6 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156 | Week 156 | -5.10 mg/L | Standard Deviation 14.68 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156 | Week 12 | -3.54 mg/L | Standard Deviation 33.57 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156 | Week 156 | -12.30 mg/L | Standard Deviation 26.69 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156 | Week 12 | -20.66 mg/L | Standard Deviation 48.35 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156 | Week 24 | -11.72 mg/L | Standard Deviation 23.54 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156 | Week 48 | -12.57 mg/L | Standard Deviation 24.23 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156 | Week 96 | -13.88 mg/L | Standard Deviation 25.96 |
Secondary
Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Activity joint count-71 was calculated as sum (joints with active arthritis)\*(71/number of joints with assessment).
Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -16.66 joint | Standard Error 1.497 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -16.47 joint | Standard Error 1.682 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -17.24 joint | Standard Error 1.547 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -18.65 joint | Standard Error 2.334 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -15.15 joint | Standard Error 1.511 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -13.88 joint | Standard Error 2.495 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -12.38 joint | Standard Error 1.519 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -13.26 joint | Standard Error 1.575 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -13.73 joint | Standard Error 1.618 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -13.79 joint | Standard Error 1.751 |
Secondary
Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. The CHAQ questionnaire consists of 30 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain is scored on a 4 point scale ranges from 0 to 3: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). An additional response of not applicable is available to indicate activities the participant is unable to perform because he/she is too young. The CHAQ-DI total score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst). Higher scores indicate worse outcome.
Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -0.90 units on a scale | Standard Error 0.096 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -0.92 units on a scale | Standard Error 0.109 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -0.88 units on a scale | Standard Error 0.084 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -1.07 units on a scale | Standard Error 0.163 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -0.77 units on a scale | Standard Error 0.092 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -1.20 units on a scale | Standard Error 0.169 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -0.74 units on a scale | Standard Error 0.113 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -0.95 units on a scale | Standard Error 0.132 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -1.08 units on a scale | Standard Error 0.119 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -1.13 units on a scale | Standard Error 0.136 |
Secondary
Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Serum concentrations of hs-CRP was determined to assess the PD effects of sarilumab.
Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -8.54 mg/L | Standard Error 3.151 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -9.39 mg/L | Standard Error 3.608 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -9.93 mg/L | Standard Error 3.505 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -5.10 mg/L | Standard Error 3.671 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -3.84 mg/L | Standard Error 5.437 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -12.30 mg/L | Standard Error 6.672 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -20.66 mg/L | Standard Error 9.304 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -11.72 mg/L | Standard Error 4.371 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -12.57 mg/L | Standard Error 4.664 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -13.88 mg/L | Standard Error 5.414 |
Secondary
Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Limited motion joint count was calculated as sum (joints with limited motion)\*(67/number of joints with assessment).
Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -11.29 joint | Standard Error 2.203 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -9.71 joint | Standard Error 1.249 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -10.40 joint | Standard Error 1.33 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -10.99 joint | Standard Error 1.498 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -11.14 joint | Standard Error 1.661 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -10.42 joint | Standard Error 1.493 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -10.73 joint | Standard Error 1.525 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -9.21 joint | Standard Error 1.54 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -11.81 joint | Standard Error 2.55 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -10.63 joint | Standard Error 1.559 |
Secondary
Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Participant/parent assessment of overall well-being was rated on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome.
Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -4.38 units on a scale | Standard Error 0.313 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -4.36 units on a scale | Standard Error 0.387 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -4.21 units on a scale | Standard Error 0.356 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -4.19 units on a scale | Standard Error 0.738 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -3.73 units on a scale | Standard Error 0.335 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -5.01 units on a scale | Standard Error 0.636 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -4.01 units on a scale | Standard Error 0.435 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -4.39 units on a scale | Standard Error 0.475 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -4.64 units on a scale | Standard Error 0.51 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -5.09 units on a scale | Standard Error 0.521 |
Secondary
Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Physician global assessment of disease activity was assessed on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome.
Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -4.99 units on a scale | Standard Error 0.237 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -5.30 units on a scale | Standard Error 0.306 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -5.27 units on a scale | Standard Error 0.263 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -5.66 units on a scale | Standard Error 0.396 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -4.50 units on a scale | Standard Error 0.248 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156 | Week 156 | -5.73 units on a scale | Standard Error 0.437 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156 | Week 12 | -4.09 units on a scale | Standard Error 0.367 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156 | Week 24 | -5.01 units on a scale | Standard Error 0.341 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156 | Week 48 | -5.25 units on a scale | Standard Error 0.321 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156 | Week 96 | -5.35 units on a scale | Standard Error 0.347 |
Secondary
Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156
The JADAS is used for assessment of disease activity, and it includes 4 measures: Physician global assessment of disease activity (VAS range: 0 to10; where 0= no activity and 10= maximum activity), parent/participant global assessment of well-being (VAS range: 0 to 10; where 0= no activity and10= maximum activity), count of joints with active disease (range: 0 to 27; where 0= no activity and 27= maximum activity), and index of inflammation determined by hs-CRP or ESR (normalized scale range: 0 to 10; where 0= no disease activity and 10= maximum disease activity). The JADAS total score is calculated as the simple sum of the scores of its 4 components. The total score ranges from 0 to 57 where 0= no disease activity and 57= maximum disease activity. Higher scores indicate higher disease activity. Clinical JADAS-27 is without CRP or ESR component and score ranges from 0 to 47 where 0= no disease activity and 47= maximum disease activity.
Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-ESR: Week 156 | -23.2 units on a scale | Standard Error 2.06 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-CRP: Week 96 | -21.9 units on a scale | Standard Error 1.58 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-ESR: Week 24 | -21.9 units on a scale | Standard Error 1.32 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-CRP: Week 156 | -21.8 units on a scale | Standard Error 2.01 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-CRP: Week 12 | -18.2 units on a scale | Standard Error 1.26 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | Clinical JADAS-27: Week 12 | -17.9 units on a scale | Standard Error 1.19 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-ESR: Week 96 | -22.4 units on a scale | Standard Error 1.69 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | Clinical JADAS-27: Week 24 | -20.5 units on a scale | Standard Error 1.14 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-CRP: Week 24 | -20.9 units on a scale | Standard Error 1.2 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | Clinical JADAS-27: Week 48 | -21.0 units on a scale | Standard Error 1.22 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-ESR: Week 48 | -22.3 units on a scale | Standard Error 1.45 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | Clinical JADAS-27: Week 96 | -21.2 units on a scale | Standard Error 1.52 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-CRP: Week 48 | -21.6 units on a scale | Standard Error 1.23 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | Clinical JADAS-27: Week 156 | -21.2 units on a scale | Standard Error 1.85 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-ESR: Week 12 | -18.9 units on a scale | Standard Error 1.46 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | Clinical JADAS-27: Week 156 | -19.3 units on a scale | Standard Error 2.14 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-ESR: Week 12 | -16.9 units on a scale | Standard Error 1.51 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-ESR: Week 24 | -18.3 units on a scale | Standard Error 1.72 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-ESR: Week 48 | -19.4 units on a scale | Standard Error 1.61 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-ESR: Week 96 | -20.4 units on a scale | Standard Error 1.84 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-ESR: Week 156 | -20.6 units on a scale | Standard Error 2.57 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-CRP: Week 12 | -16.3 units on a scale | Standard Error 1.42 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-CRP: Week 24 | -18.8 units on a scale | Standard Error 1.53 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-CRP: Week 48 | -19.4 units on a scale | Standard Error 1.58 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-CRP: Week 96 | -20.1 units on a scale | Standard Error 1.5 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | JADAS-27-CRP: Week 156 | -20.2 units on a scale | Standard Error 2.24 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | Clinical JADAS-27: Week 12 | -16.0 units on a scale | Standard Error 1.32 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | Clinical JADAS-27: Week 24 | -18.0 units on a scale | Standard Error 1.46 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | Clinical JADAS-27: Week 48 | -18.8 units on a scale | Standard Error 1.49 |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156 | Clinical JADAS-27: Week 96 | -19.5 units on a scale | Standard Error 1.6 |
Secondary
Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156
JIA ACR100 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 100% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%.
Time frame: Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156 | Week 24 | 23.1 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156 | Week 96 | 47.2 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156 | Week 48 | 42.1 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156 | Week 156 | 52.9 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156 | Week 12 | 12.8 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156 | Week 156 | 87.5 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156 | Week 12 | 24.1 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156 | Week 24 | 48.1 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156 | Week 48 | 53.8 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156 | Week 96 | 70.8 percentage of participants with response |
Secondary
Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156
JIA ACR30 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 30% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%.
Time frame: Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156 | Week 24 | 100 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156 | Week 96 | 97.2 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156 | Week 48 | 100 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156 | Week 156 | 94.1 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156 | Week 12 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156 | Week 156 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156 | Week 12 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156 | Week 24 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156 | Week 48 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156 | Week 96 | 100 percentage of participants with response |
Secondary
Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156
JIA ACR50 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 50% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%.
Time frame: Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156 | Week 24 | 100 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156 | Week 96 | 97.2 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156 | Week 48 | 100 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156 | Week 156 | 94.1 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156 | Week 12 | 94.9 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156 | Week 156 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156 | Week 12 | 96.6 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156 | Week 24 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156 | Week 48 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156 | Week 96 | 100 percentage of participants with response |
Secondary
Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156
JIA ACR70 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 70% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%.
Time frame: Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156 | Week 24 | 87.2 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156 | Week 96 | 97.2 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156 | Week 48 | 89.5 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156 | Week 156 | 94.1 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156 | Week 12 | 74.4 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156 | Week 156 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156 | Week 12 | 89.7 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156 | Week 24 | 96.3 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156 | Week 48 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156 | Week 96 | 100 percentage of participants with response |
Secondary
Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156
JIA ACR90 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 90% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%.
Time frame: Weeks 12, 24, 48, 96, and 156
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Participants in Cohorts 1 and 3 only participated in portion 1 and then switched to Dose 2 after the dose is selected. Therefore, only Cohort 2 participants analyzed at baseline and specific time points are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156 | Week 24 | 64.1 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156 | Week 96 | 80.6 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156 | Week 48 | 68.4 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156 | Week 156 | 76.5 percentage of participants with response |
| Cohort 1: >= 30 kg and <= 60 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156 | Week 12 | 43.6 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156 | Week 156 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156 | Week 12 | 48.3 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156 | Week 24 | 74.1 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156 | Week 48 | 88.5 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156 | Week 96 | 95.8 percentage of participants with response |
Secondary
Cohorts 1 and 3: Change From Baseline in High-Sensitivity C-reactive Protein (Hs-CRP) at Week 12
Serum concentrations of hs-CRP was determined to assess the Pharmacodynamic (PD) effects of sarilumab. The values reported are mean and standard deviation.
Time frame: Baseline (Day 1) and Week 12
Population: All treated population included participants who signed informed consent and received at least 1 dose of the study treatment. Only participants analyzed at baseline and Week 12 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in High-Sensitivity C-reactive Protein (Hs-CRP) at Week 12 | -1.00 mg/L | Standard Deviation 2.53 |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in High-Sensitivity C-reactive Protein (Hs-CRP) at Week 12 | -0.52 mg/L | Standard Deviation 3.64 |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in High-Sensitivity C-reactive Protein (Hs-CRP) at Week 12 | -5.71 mg/L | Standard Deviation 8.9 |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in High-Sensitivity C-reactive Protein (Hs-CRP) at Week 12 | -6.83 mg/L | Standard Deviation 11.74 |
Secondary
Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Week 12
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using visual analog scale (VAS), Childhood Health Questionnaire Disability Index (CHAQ-DI) and hs-CRP. Activity joint count-71 was calculated as sum (joints with active arthritis)\*(71/number of joints with assessment).
Time frame: Baseline (Day 1) and Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at baseline and Week 12 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Week 12 | -14.40 joint | Standard Error 2.159 |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Week 12 | -11.20 joint | Standard Error 2.871 |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Week 12 | -16.50 joint | Standard Error 4.137 |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Week 12 | -14.40 joint | Standard Error 5.573 |
Secondary
Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Week 12
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. The CHAQ questionnaire consists of 30 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain is scored on a 4 point scale ranges from 0 to 3: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). An additional response of not applicable is available to indicate activities the participant is unable to perform because he/she is too young. The CHAQ-DI total score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst). Higher scores indicate worse outcome.
Time frame: Baseline (Day 1) and Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at baseline and Week 12 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Week 12 | -0.80 units on a scale | Standard Error 0.242 |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Week 12 | -1.08 units on a scale | Standard Error 0.239 |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Week 12 | -0.42 units on a scale | Standard Error 0.173 |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Week 12 | -0.75 units on a scale | Standard Error 0.213 |
Secondary
Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Week 12
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Serum concentrations of hs-CRP was determined to assess the PD effects of sarilumab.
Time frame: Baseline (Day 1) and Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at baseline and Week 12 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Week 12 | -1.00 mg/L | Standard Error 1.13 |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Week 12 | -1.67 mg/L | Standard Error 1.139 |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Week 12 | -5.71 mg/L | Standard Error 3.633 |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Week 12 | -2.54 mg/L | Standard Error 1.845 |
Secondary
Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Week 12
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Limited motion joint count was calculated as sum (joints with limited motion)\*(67/number of joints with assessment).
Time frame: Baseline (Day 1) and Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at baseline and Week 12 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Week 12 | -7.80 joint | Standard Error 2.083 |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Week 12 | -5.80 joint | Standard Error 2.267 |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Week 12 | -7.83 joint | Standard Error 2.6 |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Week 12 | -13.00 joint | Standard Error 4.219 |
Secondary
Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Week 12
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Participant/parent assessment of overall well-being was rated on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome.
Time frame: Baseline (Day 1) and Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at baseline and Week 12 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Week 12 | -3.30 units on a scale | Standard Error 1.014 |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Week 12 | -3.16 units on a scale | Standard Error 1.364 |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Week 12 | -3.05 units on a scale | Standard Error 0.992 |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Week 12 | -5.00 units on a scale | Standard Error 0.969 |
Secondary
Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Week 12
The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Physician global assessment of disease activity was assessed on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome.
Time frame: Baseline (Day 1) and Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at baseline and Week 12 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Week 12 | -3.56 units on a scale | Standard Error 0.969 |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Week 12 | -6.30 units on a scale | Standard Error 0.397 |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Week 12 | -4.55 units on a scale | Standard Error 0.509 |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Week 12 | -5.68 units on a scale | Standard Error 1.163 |
Secondary
Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12
The JADAS is used for assessment of disease activity, and it includes 4 measures: Physician global assessment of disease activity (VAS range: 0 to10; where 0= no activity and 10= maximum activity), parent/participant global assessment of well-being (VAS range: 0 to 10; where 0= no activity and10= maximum activity), count of joints with active disease (range: 0 to 27; where 0= no activity and 27= maximum activity), and index of inflammation determined by hs-CRP or ESR (normalized scale range: 0 to 10; where 0= no disease activity and 10= maximum disease activity). The JADAS total score is calculated as the simple sum of the scores of its 4 components. The total score ranges from 0 to 57 where 0= no disease activity and 57= maximum disease activity. Higher scores indicate higher disease activity. Clinical JADAS-27 is without CRP or ESR component and score ranges from 0 to 47 where 0= no disease activity and 47= maximum disease activity.
Time frame: Baseline (Day 1) and Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at baseline and Week 12 are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | JADAS-27-ESR: Week 12 | -15.4 units on a scale | Standard Error 2.98 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | Clinical JADAS-27: Week 12 | -16.1 units on a scale | Standard Error 2.77 |
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | JADAS-27-CRP: Week 12 | -16.0 units on a scale | Standard Error 2.78 |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | JADAS-27-ESR: Week 12 | -19.1 units on a scale | Standard Error 3.05 |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | Clinical JADAS-27: Week 12 | -18.1 units on a scale | Standard Error 2.62 |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | JADAS-27-CRP: Week 12 | -18.1 units on a scale | Standard Error 2.62 |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | JADAS-27-CRP: Week 12 | -18.5 units on a scale | Standard Error 3.42 |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | JADAS-27-ESR: Week 12 | -20.0 units on a scale | Standard Error 3.82 |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | Clinical JADAS-27: Week 12 | -18.3 units on a scale | Standard Error 3.28 |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | JADAS-27-ESR: Week 12 | -19.4 units on a scale | Standard Error 6.01 |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | Clinical JADAS-27: Week 12 | -21.1 units on a scale | Standard Error 4.96 |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12 | JADAS-27-CRP: Week 12 | -21.1 units on a scale | Standard Error 4.96 |
Secondary
Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Week 12
JIA ACR100 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 100% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%.
Time frame: Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at Week 12 are reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Week 12 | 0 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Week 12 | 0 percentage of participants with response |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Week 12 | 33.3 percentage of participants with response |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Week 12 | 40.0 percentage of participants with response |
Secondary
Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Week 12
JIA ACR50 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 50% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%.
Time frame: Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at Week 12 are reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Week 12 | 80.0 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Week 12 | 100 percentage of participants with response |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Week 12 | 100 percentage of participants with response |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Week 12 | 100 percentage of participants with response |
Secondary
Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Week 12
JIA ACR70 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 70% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%.
Time frame: Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at Week 12 are reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Week 12 | 60.0 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Week 12 | 40.0 percentage of participants with response |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Week 12 | 100 percentage of participants with response |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Week 12 | 100 percentage of participants with response |
Secondary
Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Week 12
JIA ACR90 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 90% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%.
Time frame: Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at Week 12 are reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Week 12 | 60.0 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Week 12 | 20.0 percentage of participants with response |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Week 12 | 66.7 percentage of participants with response |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Week 12 | 60.0 percentage of participants with response |
Secondary
Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology (JIA ACR) 30 Response at Week 12
JIA ACR30 response was defined as a participant with at least 3 out of the 6 JIA core set variables with \>= 30% improvement from baseline with no more than 1 of the remaining variables worsened by \>= 30%.
Time frame: Week 12
Population: The efficacy analysis set included all participants who received at least 1 dose of sarilumab. Only participants analyzed at Week 12 are reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology (JIA ACR) 30 Response at Week 12 | 100 percentage of participants with response |
| Cohort 1: < 30 kg and >= 10 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology (JIA ACR) 30 Response at Week 12 | 100 percentage of participants with response |
| Cohort 2: >= 30 kg and <= 60 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology (JIA ACR) 30 Response at Week 12 | 100 percentage of participants with response |
| Cohort 2: < 30 kg and >= 10 kg | Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology (JIA ACR) 30 Response at Week 12 | 100 percentage of participants with response |
Secondary
Number of Participants With Local Site Reactions
Participants were observed for at least 30 minutes after each study treatment administration either on site or at home and any local reactions were noted in the diary regardless of being clinically significant.
Time frame: From the first administration of study treatment (Day 1) up to end of treatment period, maximum of 156 weeks for portions 1 and 2 and 96 weeks for portion 3
Population: The Safety analysis set included all participants who received at least 1 dose or part of a dose of the study treatment, analyzed according to the treatment actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Number of Participants With Local Site Reactions | 1 Participants |
| Cohort 1: < 30 kg and >= 10 kg | Number of Participants With Local Site Reactions | 0 Participants |
| Cohort 2: >= 30 kg and <= 60 kg | Number of Participants With Local Site Reactions | 21 Participants |
| Cohort 2: < 30 kg and >= 10 kg | Number of Participants With Local Site Reactions | 19 Participants |
| Cohort 3: >= 30 kg and <= 60 kg | Number of Participants With Local Site Reactions | 3 Participants |
| Cohort 3: < 30 kg and >= 10 kg | Number of Participants With Local Site Reactions | 1 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
An adverse events (AEs) is any untoward medical occurrence in a participant or in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with the study treatment. An SAE is any untoward medical occurrence that at any dose results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect or is an important medical event. TEAEs are defined as AEs that develop or worsen during the on-treatment period \[that is, from the time of first dose of study treatment up to 6 weeks after the last administration of the study treatment\].
Time frame: From the first administration of study treatment (Day 1) up to end of treatment period, maximum of 156 weeks for portions 1 and 2 and 96 weeks for portion 3
Population: The Safety analysis set included all participants who received at least 1 dose or part of a dose of the study treatment, analyzed according to the treatment actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: >= 30 kg and <= 60 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any TEAE | 7 Participants |
| Cohort 1: >= 30 kg and <= 60 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any treatment emergent SAE | 2 Participants |
| Cohort 1: < 30 kg and >= 10 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any TEAE | 6 Participants |
| Cohort 1: < 30 kg and >= 10 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any treatment emergent SAE | 0 Participants |
| Cohort 2: >= 30 kg and <= 60 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any TEAE | 40 Participants |
| Cohort 2: >= 30 kg and <= 60 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any treatment emergent SAE | 3 Participants |
| Cohort 2: < 30 kg and >= 10 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any TEAE | 30 Participants |
| Cohort 2: < 30 kg and >= 10 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any treatment emergent SAE | 3 Participants |
| Cohort 3: >= 30 kg and <= 60 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any TEAE | 5 Participants |
| Cohort 3: >= 30 kg and <= 60 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any treatment emergent SAE | 0 Participants |
| Cohort 3: < 30 kg and >= 10 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any TEAE | 9 Participants |
| Cohort 3: < 30 kg and >= 10 kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any treatment emergent SAE | 0 Participants |