A Safety, Efficacy And Pharmacokinetics Study Of Tofacitinib In Pediatric Patients With sJIA

Study Overview
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Brief Summary
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A randomized withdrawal study in which responders to open-label treatment with tofacitinib will be randomized in a 1:1 ratio to tofacitinib or placebo in a double-blind phase. In the double-blind phase time to sJIA flare will be evaluated as primary endpoint and subjects will be discontinued once they experience sJIA flare. Once 31 flares are reported the study will be completed.

Official Title
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EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF TOFACITINIB FOR TREATMENT OF SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS (SJIA) WITH ACTIVE SYSTEMIC FEATURES IN CHILDREN AND ADOLESCENT SUBJECTS

Conditions
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Arthritis Juvenile Idiopathic

Intervention / Treatment
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* Drug: In open-label phase: treatment with tofacitinib
* Drug: In double-blind phase: treatment with tofacitinib or placebo in 1:1 ratio


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: active sJIA disease according to ILAR criteria before screening and at baseline (Day 1); Treatment with stable doses of methotrexate (MTX) ≤25 mg/week or ≤20 mg/m2/week, whichever is lower, is permitted; Treatment with a stable dose of oral prednisone ≤1 mg/kg/day up to a maximum of 30 mg/day, or equivalent, for at least 1 week before the first study drug dose is permitted. Exclusion Criteria: Previous juvenile idiopathic arthritis (JIA) treatment with tofacitinib. Current symptoms or findings of myocarditis, endocarditis or more than minimal pericardial effusion associated with systemic juvenile idiopathic arthritis (sJIA). Current symptoms or findings of more than minimal pleuritis with sJIA. Current infection or serious infection within 3 months of study enrollment.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tofacitinib 5 mg BID<br>oral, twice daily, tablet or solution. | Drug: In open-label phase: treatment with tofacitinib<br>* Treatment with investigational drug<br>* Other names: Xeljanz;Drug: In double-blind phase: treatment with tofacitinib or placebo in 1:1 ratio<br>* Treatment with investigational drug or placebo<br>* Other names: Xeljanz;|
| Placebo Comparator: Placebo<br> | Drug: In double-blind phase: treatment with tofacitinib or placebo in 1:1 ratio<br>* Treatment with investigational drug or placebo<br>* Other names: Xeljanz;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to flare | Time to sJIA disease flare in the double-blind phase | Up to 82 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of disease flare in double-blind phase | disease flare frequency by visit in the double-blind phase. | Up to 82 weeks after randomization | 
| Achievement of corticosteroid tapering at the end of the open-label phase | Rate of successful corticosteroid tapering. | 12 to 40 weeks | 
| Achievement of a corticosteroid dose of 0.2 mg/kg/day or 10 mg/day (whichever is lower) at the end of the open label treatment period |  | 12 to 40 weeks | 
| Adapted sJIA ACR 30/50/70/90/100 response at every visit from Day 7 onward in the open label and double blind phase. |  | Up to 82 weeks after randomization | 
| Fever (Temp >38 Degrees Celsius) attributed to sJIA at Day 3, Day 7 and Day 14 of the open label phase. |  | Day 3, Day 7, Day 14 | 
| CRP ≤ 10 mg/L at every visit of the open label phase. |  | 12 to 40 weeks | 
| Absence of fever, defined as absence of fever due to sJIA in the week preceding the assessment at every visit from Day 7 onward in the open label and double blind phase. |  | Up to 82 weeks after randomization. | 
| Time to first Adapted JIA ACR 30 response in Part 1 of the open label phase. |  | 12 to 40 weeks | 
| Change from baseline in Juvenile Arthritis Disease Activity Score (JADAS 27) at every visit from Day 7 onward in the open label and double blind phase. |  | Up to 82 weeks after randomization. | 
| Change from baseline in each JIA ACR core variable at every visit from Day 7 onward in the open label and double blind phase. |  | Up to 82 weeks after randomization. | 
| Change from baseline in Child Health Questionnaire (CHQ) responses at the end of Part 1 and Part 2 of the open label phase, at randomization and every 3 months thereafter. |  | Up to 82 weeks after randomization. | 
| Change from baseline in Child Health Assessment Questionnaire (CHAQ) at every visit from Day 7 onward in the open label and double blind phase. |  | Up to 82 weeks after randomization. | 
| Occurrence of inactive disease status and minimal disease activity clinical remission at every visit from Day 7 onward (JADAS 27) in the open label and double blind phase. |  | Up to 82 weeks after randomization. | 
| Occurrence of inactive disease status and clinical remission at every visit from Day 7 onward (JIA ACR) in the open label and double blind phase. |  | Up to 82 weeks after randomization. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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systemic Juvenile Idiopathic Arthritis, Xeljanz, Tofacitinib, sJIA, CP-690 550