The primary objective of this study is to evaluate the pharmacokinetics (PK) of olokizumab (OKZ) in patients with polyarticular juvenile idiopathic arthritis aged \>2 and \<18 years in two doses (64 mg or 48 mg every 4 weeks) depending on patient's weight. Secondary objectives are to evaluate the pharmacodynamic (PD) profile, the long-term efficacy and safety of olokizumab in patients with polyarticular juvenile idiopathic arthritis aged \>2 and \<18 years.
Study informed consent form voluntarily and independently signed by patient legal representative
Study assent form voluntarily and independently signed by minor study subject (patient)
Male or female patients aged ≥12 and <18 years (cohort 1 - subgroup A) or >2 and <12 years (cohort 1 - subgroup B) or >2 and <18 years (cohort 2) at the time of screening initiation and on Day 0
Body weight at the start of screening and on Day 0 ≥45 kg (cohort 1 - subgroup A) or ≥30 and <45 kg (cohort 1 - subgroup B) or ≥18 and <30 kg (cohort 2)
Prior use of any drug that acts directly on IL-6 or IL-6R
If methotrexate is administered - any change in dose or in a formulation within 6 weeks prior to Day 0
Previous therapy with marketed or experimental conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic disease-modifying anti-rheumatic drugs (bDMARDs) within less than 5 elimination half-lives
Use of oral steroids in the doses above 0.2 mg/kg or 10 mg/day of prednisolone daily, whatever is lower, or a change in dose within 2 weeks prior to Day 0, or use of parenteral or topical steroids within 4 weeks prior to Day 0
Parallel
OKZ q4w
DrugSubcutaneous (SC) injections of OKZ every 4 weeks; Olokizumab is a sterile solution for subcutaneous injection
OKZ q4w
DrugSC injections of OKZ 48 mg every 4 weeks; Olokizumab is a sterile solution for subcutaneous injection
Olokizumab Cmax (W24) (maximum concentration) over 24 weeks
The Cmax is defined as maximum serum concentration of olokizumab
Olokizumab area under the concentration-time curve (AUC0-W24) over 24 weeks
The AUC0-W24 is defined as area under the plasma concentration-time curve over the dosing interval (AUC0-W24)
Minimum drug concentration at steady state (Ctrough,ss)
The Ctrough is defined as concentration observed before treatment administration during repeated dosing at steady state
Maximum concentration (Cmax) of olokizumab after the first administration
The Cmax is defined as maximum serum concentration of olokizumab
Time to reach maximum concentration (tmax) of olokizumab after the first administration
T(max) is defined as the time it takes for a drug to reach the maximum concentration (Cmax) after administration of olokizumab
The area under the concentration-time curve (AUCtau) of olokizumab over the study period
The AUCtau is defined as area under the plasma concentration-time curve over the dosing interval (AUC0-tau)
Treatment response, based on Juvenile idiopathic Arthritis American College of Rheumatology (JIA ACR) 30, 50, 70 and 90 criteria over the study period
* JIA ACR 30 responder is 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% * JIA ACR 50 responder is 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% * JIA ACR 70 responder is 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% * JIA ACR 90 responder is 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%
Changes in Juvenile Arthritis Disease Activity Score-10 (JADAS-10) over the study period
The JADAS-10 includes 4 measures: 1. physician global assessment of disease activity (VAS range: 0 to 10; where 0= no activity and 10= maximum activity) 2. parent/participant global assessment of well-being (VAS range: 0 to 10; where 0= no activity and 10= maximum activity) 3. count of active joints (range: 0 to 10; where 0= no activity and 10= maximum activity) 4. index of inflammation determined by high-sensitivity C-reactive protein (hs-CRP) or erythrocyte sedimentation rate (ESR) (normalized scale range: 0 to 10; where 0= no disease activity and 10= maximum disease activity)
Changes in Juvenile Arthritis Disease Activity Score-27 (JADAS-27) over the study period
The JADAS-27 includes 4 measures: 1. physician global assessment of disease activity (VAS range: 0 to 10; where 0= no activity and 10= maximum activity) 2. parent/participant global assessment of well-being (VAS range: 0 to 10; where 0= no activity and 10= maximum activity) 3. count of active joints (range: 0 to 27; where 0= no activity and 27= maximum activity) 4. index of inflammation determined by high-sensitivity C-reactive protein (hs-CRP) or erythrocyte sedimentation rate (ESR) (normalized scale range: 0 to 10; where 0= no disease activity and 10= maximum disease activity)
Changes in Juvenile Arthritis Disease Activity Score-71 (JADAS-71) over the study period
The JADAS-71 includes 4 measures: 1. physician global assessment of disease activity (VAS range: 0 to 10; where 0= no activity and 10= maximum activity) 2. parent/participant global assessment of well-being (VAS range: 0 to 10; where 0= no activity and 10= maximum activity) 3. count of active joints (range: 0 to 71; where 0= no activity and 71= maximum activity) 4. index of inflammation determined by high-sensitivity C-reactive protein (hs-CRP) or erythrocyte sedimentation rate (ESR) (normalized scale range: 0 to 10; where 0= no disease activity and 10= maximum disease activity)
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R-Pharm International, LLC
Lead sponsor
R-Pharm
Collaborator
Keystat, LLC
Collaborator
Exacte Labs LLC
Collaborator
