Juvenile Idiopathic Arthritis
Conditions
Keywords
olokizumab, interleukin-6 (IL-6), C-reactive protein (CRP), Musculoskeletal Diseases, Autoimmune Diseases, Rheumatic Diseases Connective Tissue Diseases, Arthritis, Juvenile Arthritis
Brief summary
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.
Detailed description
This study is a multicenter, open-label, non-randomized, uncontrolled study with an interim analysis of endpoints after 12 weeks of therapy, a final analysis of endpoints after 24 weeks of therapy, and an additional analysis at the end of all study visits. The total number of study subjects screened is 71 subjects. Up to 50 patients will begin treatment. This study includes: 1. A screening period of up to 2 weeks 2. A main period of open label treatment from Week 0 to Week 24 (24 weeks) 3. A period of extended open label treatment from Week 24 to Week 164 (140 weeks) 4. Safety follow-up period from Week 165 to Week 186 (22 weeks) The total study duration for patients is approximately 188 weeks (including the screening period).
Interventions
DRUGOKZ q4w
Subcutaneous (SC) injections of OKZ every 4 weeks; Olokizumab is a sterile solution for subcutaneous injection
Sponsors
R-Pharm International, LLC
R-Pharm
Keystat, LLC
Exacte Labs LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients treat with olokizumab SC q4w
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Study informed consent form voluntarily and independently signed by patient legal representative 2. Study assent form voluntarily and independently signed by minor study subject (patient) 3. 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 4. 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) 5. A reliable diagnosis of juvenile idiopathic arthritis (JIA) according to the JIA International League of Associations for Rheumatology (ILAR) 1 criteria with onset before the age of 16 years: 1. Seropositive or seronegative polyarthritis (pJIA) ≥3 months before screening, or 2. Systemic JIA (sJIA) for ≥3 months before screening, provided that joint symptoms persist without active systemic manifestations for ≥3 months before screening, or 3. Extended oligoarticular JIA (оJIA) ≥3 months before screening 6. American College of Radiology (ACR) criteria of active polyarthritis are met: 5 or more active joints at screening and on Day 0 7. C-reactive protein (CRP) level on screening or in anamnesis, not associated with alternative causes of increase other than the activity of the underlying disease, ≥6 mg/l 8. Intolerance or failure of methotrexate in the dose of ≥15 mg/m\^2/week (or less, in a case of documented intolerance of higher doses) for ≥3 months in medical history
Exclusion criteria
1. Prior use of any drug that acts directly on IL-6 or IL-6R 2. If methotrexate is administered - any change in dose or in a formulation within 6 weeks prior to Day 0 3. 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 4. 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 5. Change in dose of a non-steroidal anti-inflammatory drug (NSAID) within ≤2 weeks prior to Day 0 6. Vaccination with live vaccines within 6 weeks before baseline, or planned vaccination with live vaccines during the study and/or within 6 weeks after the last olokizumab administration 7. Active uveitis at screening or uveitis exacerbation within 24 weeks before screening 8. Laboratory abnormalities (creatinine ≥1 mg/dL (88 mM) for children aged 12 or ≥1.2 mg/dL (106 mM) for children aged 13 and older; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥1.5 х upper limit normal (ULN); platelets \<180,000/mm\^3; white blood count (WBC) \<4000/mm\^3; neutrophils \<2000/mm\^3; hemoglobin ≤80 g/L 9.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Olokizumab Cmax (W24) (maximum concentration) over 24 weeks | 24 weeks | The Cmax is defined as maximum serum concentration of olokizumab |
| Olokizumab area under the concentration-time curve (AUC0-W24) over 24 weeks | 24 weeks | The AUC0-W24 is defined as area under the plasma concentration-time curve over the dosing interval (AUC0-W24) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum drug concentration at steady state (Ctrough,ss) | 24 weeks | 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 | 4 weeks | The Cmax is defined as maximum serum concentration of olokizumab |
| Time to reach maximum concentration (tmax) of olokizumab after the first administration | 4 weeks | 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 | 12, 24, 72 weeks | The AUCtau is defined as area under the plasma concentration-time curve over the dosing interval (AUC0-tau) |
| Concentration before the next dose of olokizumab (Ctrough) | 12, 24, 72 weeks | The Ctrough is defined as concentration observed before the next dose of olokizumab during repeated dosing |
| Time to steady state (tss) | 12, 24, 72 weeks | Time to reach steady state will be assessed both graphically and statistically. The statistical approach will involve fitting a repeated measures linear mixed model to natural log-transformed data, using Helmert contrasts to compare earlier and later weeks, and identifying the earliest week where the mean concentration difference is not statistically significant |
| Area under the concentration-time curve in the steady state (AUCss) | 24, 72 weeks | The АUCss is defined as the area under the curve of the plasma concentration of the drug in the dosing interval at steady state |
Countries
Russia
Contacts
CONTACTAnna Karpenko
CONTACTDarya Bukhanova
STUDY_DIRECTORMikhail Samsonov
R-Pharm
Outcome results
None listed