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| Name | Class |
|---|---|
| R-Pharm | INDUSTRY |
| Keystat, LLC | INDUSTRY |
| Exacte Labs LLC | INDUSTRY |
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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.
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:
The total study duration for patients is approximately 188 weeks (including the screening period).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: OKZ 64 mg q4w | Experimental | SC injections q4w-Cohort 1 |
|
| Arm 2: OKZ 48 mg q4w | Experimental | SC injections q4w-Cohort 2 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| OKZ q4w | Drug | Subcutaneous (SC) injections of OKZ every 4 weeks; Olokizumab is a sterile solution for subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Olokizumab Cmax (W24) (maximum concentration) over 24 weeks | The Cmax is defined as maximum serum concentration of olokizumab | 24 weeks |
| 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) | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Minimum drug concentration at steady state (Ctrough,ss) | The Ctrough is defined as concentration observed before treatment administration during repeated dosing at steady state | 24 weeks |
| Maximum concentration (Cmax) of olokizumab after the first administration |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment response, based on Juvenile idiopathic Arthritis American College of Rheumatology (JIA ACR) 30, 50, 70 and 90 criteria over the study period |
|
Inclusion Criteria:
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)
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:
American College of Radiology (ACR) criteria of active polyarthritis are met: 5 or more active joints at screening and on Day 0
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
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anna Karpenko | Contact | +7 (495) 956-79-37 | 1552 | karpenko@rpharm.ru |
| Darya Bukhanova | Contact | +7 (495) 956-79-37 | bukhanova@rpharm.ru |
| Name | Affiliation | Role |
|---|---|---|
| Mikhail Samsonov | R-Pharm | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Federal State Budgetary Educational Institution of Higher Education "Kazan State Medical University" of the Ministry of Health of the Russian Federation | Recruiting | Kazan' | 420012 | Russia |
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Patients treat with olokizumab SC q4w
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| OKZ q4w | Drug | SC injections of OKZ 48 mg every 4 weeks; Olokizumab is a sterile solution for subcutaneous injection |
|
|
The Cmax is defined as maximum serum concentration of olokizumab |
| 4 weeks |
| 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 | 4 weeks |
| 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) | 12, 24, 72 weeks |
| Concentration before the next dose of olokizumab (Ctrough) | The Ctrough is defined as concentration observed before the next dose of olokizumab during repeated dosing | 12, 24, 72 weeks |
| Time to steady state (tss) | 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 | 12, 24, 72 weeks |
| Area under the concentration-time curve in the steady state (AUCss) | The АUCss is defined as the area under the curve of the plasma concentration of the drug in the dosing interval at steady state | 24, 72 weeks |
| 24, 72, 164 weeks |
| Changes in Juvenile Arthritis Disease Activity Score-10 (JADAS-10) over the study period | The JADAS-10 includes 4 measures:
| 24, 72, 164 weeks |
| Changes in Juvenile Arthritis Disease Activity Score-27 (JADAS-27) over the study period | The JADAS-27 includes 4 measures:
| 24, 72, 164 weeks |
| Changes in Juvenile Arthritis Disease Activity Score-71 (JADAS-71) over the study period | The JADAS-71 includes 4 measures:
| 24, 72, 164 weeks |
| Proportion of patients with minimal disease activity/inactive disease according to Juvenile Arthritis Disease Activity Score (JADAS) criteria | JADAS inactive disease is defined by a JADAS-27 score less than or equal to 1 The JADAS-27 includes 4 measures:
| 24, 72, 164 weeks |
| Changes in physician assessments of disease activity (VAS) over the study period | Physician global assessment of disease activity (VAS range: 0 to 10; where 0= no activity and 10= maximum activity). Higher scores indicate better outcome | 24, 72,164 weeks |
| Changes in patient/parent assessments of disease activity (VAS) over the study period | Parent/patient global assessment of well-being (VAS range: 0 to 10; where 0= no activity and 10= maximum activity). Higher scores indicate better outcome | 24, 72, 164 weeks |
| Changes in the number of active joints over the study period | Active joint is defined as defined as a swollen joint or, in the absence of swelling, with limited mobility accompanied by pain/tenderness | 24, 72, 164 weeks |
| Changes in the number of joints with functional limitations over the study period | Functional limitations is defined as defined as a swollen joint or, in the absence of swelling, with limited mobility accompanied by pain/tenderness | 24, 72, 164 weeks |
| Changes in the Childhood Health Assessment Questionnaire (CHAQ) disability index (DI) over the study period | 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 (the worst). Higher scores indicate worse outcome | 24, 72, 164 weeks |
| Changes in blood C-reactive Protein (CRP) concentrations over the study period | Serum concentrations of CRP is determined to assess the Pharmacodynamic (PD) effects of olokizumab | 24, 72, 164 weeks |
| Proportion of patients with clinically inactive disease during the study according to American College of Rheumatology (ACR) criteria | Clinically inactive disease is defined as no joints with active arthritis; no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy associated with JIA; absence of active uveitis; normal erythrocyte sedimentation rate (ESR) and/or C-reactive Protein (CRP); absence of disease activity according to the physician's global assessment of disease activity (VAS) scale; morning stiffness less than 15 minutes | 24, 72, 164 weeks |
| Proportion of patients with pharmacologic remission during the study according to American College of Rheumatology (ACR) criteria | Pharmacologic remission is defined as a clinically inactive disease for at least 6 months. Clinically inactive disease is defined as no joints with active arthritis; no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy associated with JIA; absence of active uveitis; normal erythrocyte sedimentation rate (ESR) and/or C-reactive Protein (CRP); absence of disease activity according to the physician's global assessment of disease activity (VAS) scale; morning stiffness less than 15 minutes | 24, 72, 164 weeks |
| Proportion of patients with exacerbation of Juvenile Idiopathic Arthritis (JIA) according to Pediatric Rheumatology Collaborative Study Group (PRCSG)-Paediatric Rheumatology International Trials Organisation (PRINTO) criteria | Proportion of patients with exacerbation of JIA according to PRCSG-PRINTO criteria during the first 24 weeks of the study and the entire study Juvenile Idiopathic Arthritis (JIA) exacerbation is defined as a deterioration of 30% or more in 3 or more of the 6 JIAcore components, with an improvement of no more than 1 item by 30% or more JIAcore components include:
| 24, 72, 164 weeks |
| Character of adverse events (AEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs) | Adverse events of special interest include:
| 168, 172, 186 weeks |
| Frequency of adverse events (AEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs) | Adverse events of special interest include:
| 168, 172, 186 weeks |
| Severity of adverse events (AEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs) | Adverse events of special interest include:
| 168, 172, 186 weeks |
| Outcomes of adverse events (AEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs) | Adverse events of special interest include:
| 168, 172, 186 weeks |
| Proportion of participants with adverse events (AEs) | Proportion of participants with AEs | 168, 172, 186 weeks |
| Proportion of participants with serious adverse events (SAEs) | Proportion of participants with SAEs | 168, 172, 186 weeks |
| Proportion of participants with clinically significant abnormalities in laboratory test results | Proportion of participants with clinically significant abnormalities in laboratory test results | 168, 172, 186 weeks |
| Number of Participants With Laboratory Abnormalities | Laboratory parameters include:
| 168, 172, 186 weeks |
| Number of Participants With Vital Sign Abnormalities | Vital Signs include: systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, body temperature. Abnormality in vital signs is based on investigator's discretion | 168, 172, 186 weeks |
| Number of Participants With Physical Examination Abnormalities | Physical examination included: skin, heart, lungs, abdomen, liver, spleen, ENT organs, lymph nodes. Abnormality in physical examination is based on investigator's discretion | 168, 172, 186 weeks |
| Proportion of participants who developed anti-drug antibodies (ADA) to the investigational product during the study and overall | Proportion of participants who developed anti-drug antibodies (ADA) to the investigational product during the study and overall | 168, 172, 186 weeks |
| Proportion of participants who developed neutralizing antibodies (nAb) to the investigational product during the study and overall | Proportion of participants who developed neutralizing antibodies (nAb) to the investigational product during the study and overall | 168, 172, 186 weeks |
| Federal State Budgetary Scientific Institution "V.A. Nasonova Research Institute of Rheumatology" | Recruiting | Moscow | 115522 | Russia |
| State Budgetary Institution of Healthcare of the City of Moscow "Morozovskaya Children's City Clinical Hospital of the Moscow City Health Department" (GBUZ "Morozovskaya DGBK DZM") | Recruiting | Moscow | 119049 | Russia |
| Federal State Autonomous Educational Institution of Higher Education First Moscow State Medical University named after I.M. Sechenov of the Ministry of Health of the Russian Federation (Sechenov University) | Recruiting | Moscow | 119435 | Russia |
| Federal State Autonomous Institution "National Medical Research Center for Children's Health" of the Ministry of Health of the Russian Federation | Recruiting | Moscow | 119991 | Russia |
| Limited Liability Company "Healthy Family Medical Center" | Recruiting | Novosibirsk | 630099 | Russia |
| Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University" of the Ministry of Health of the Russian Federation | Recruiting | Rostov-on-Don | 344022 | Russia |
| LLC "Medical Technologies" | Recruiting | Saint Petersburg | 192148 | Russia |
| Federal State Budgetary Educational Institution of Higher Education "Saratov State Medical University named after V.I. Razumovsky" of the Ministry of Health of the Russian Federation | Recruiting | Saratov | 410054 | Russia |
| Limited Liability Company "Scientific Medical Center of General Therapy and Pharmacology" (LLC "TERAPHARM") | Recruiting | Stavropol | 55000 | Russia |
| State Budgetary Healthcare Institution of the Samara Region "Tolyatti City Clinical Hospital No. 5" | Recruiting | Tolyatti | 445039 | Russia |
| Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Health of the Russian Federation | Recruiting | Ufa | 450083 | Russia |
| Federal State Budgetary Educational Institution of Higher Education "Voronezh State Medical University named after N.N. Burdenko" of the Ministry of Health of the Russian Federation | Recruiting | Voronezh | 394036 | Russia |
| State Budgetary Institution of Healthcare of the Yaroslavl Region "Regional Children's Clinical Hospital" | Recruiting | Yaroslavl | 150000 | Russia |
| ID | Term |
|---|---|
| D001171 | Arthritis, Juvenile |
| D009140 | Musculoskeletal Diseases |
| D001327 | Autoimmune Diseases |
| D001168 | Arthritis |
| ID | Term |
|---|---|
| D007592 | Joint Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007154 | Immune System Diseases |
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