Long-Term Safety Study Of Tofacitinib In Patients With Juvenile Idiopathic Arthritis

Study Overview
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Brief Summary
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Evaluate long-term safety and tolerability of tofacitinib in patients with JIA, who have previously participated in tofacitinib JIA studies.

Detailed Description
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This is a Phase 2/3, long term, open-label, follow-up study. Subjects will have previously participated in qualifying/index JIA studies of tofacitinib. Those who have already completed such participation and enroll outside the 14 day window following completion of the End of Study (EOS) Visit of the qualifying/index study will participate in a screening Visit to determine eligibility. A Baseline Visit will then occur within 28 days after the Screening Visit. For subjects who are completing participation in a qualifying study of tofacitinib and enrolling on the same day of the EOS Visit of the qualifying/index study, the EOS Visit of the qualifying/index study can be combined with the Screening and Baseline Visits for this study. The subjects who enroll within the 14 day window following completion of the EOS Visit of the qualifying/index study will participate in a combined Screening and Baseline Visit for this study. After the Baseline Visit, visits will occur at 1 month (1 month=30 days) and 3 months, then every 3 months thereafter as long as the subject remains in the study. Approximately 340 participants are projected to enroll into this open label extension study after completing a qualifying/index study in the JIA program. For subjects who entered this study from the A3921103 and A3921104 qualifying/index studies, their participation in this study ends after the first marketing approval of tofacitinib for the treatment of polyarticular course Juvenile Idiopathic Arthritis (pJIA) in any country. This study will end once the last subject, and all other subjects, who entered from index study A3921165 have completed approximately 1 year in this study, or after the first marketing approval of tofacitinib for the treatment of systemic JIA, whichever comes first. The total duration of an individual subject's participation may vary depending upon when they enter the trial.

Official Title
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A LONG-TERM, OPEN-LABEL FOLLOW-UP STUDY OF TOFACITINIB FOR TREATMENT OF JUVENILE IDIOPATHIC ARTHRITIS (JIA)

Conditions
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Juvenile Idiopathic Arthritis

Intervention / Treatment
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* Drug: Tofacitinib
* Drug: Tofacitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric subjects with JIA aged from 2 to less than 18 years who met entry criteria for the qualifying/index study and in the opinion of the investigator have sufficient evidence of JIA disease activity to warrant use of tofacitinib as a DMARD. Subjects turning 18 years of age during participation in the qualifying/index study or subsequently will be eligible for participation in this study. The subject has discontinued disallowed concomitant medications for the required time prior to the first dose of study drug, as defined in Appendix 1, and is taking only those concomitant medications in doses and frequency allowed by the protocol. Fertile male subjects and female subjects of childbearing potential who are, in the opinion of the investigator, sexually active and at risk for pregnancy with their partner(s) must be using a highly effective method of contraception as outlined in this protocol throughout the study and for at least 28 days after the last dose of study medication. Subjects must have previously completed participation in a qualifying study of tofacitinib for the treatment of JIA. Subjects who have required earlier discontinuation of treatment in a qualifying study for reasons other than tofacitinib related serious adverse events may be eligible. Exclusion Criteria: persistent oligoarthritis, and undifferentiated JIA. Infections: Chronic infections. Any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within the 3 months prior to the first dose of study drug. Any treated infections within 2 weeks of baseline visit. A subject known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus. History of infected joint prosthesis with prosthesis still in situ. History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tofacitinib<br>All patients will be in tofacitinib treatment group. | Drug: Tofacitinib<br>* Tofacitinib will be administered orally BID (twice daily) approximately 12 hours (±2 hours) apart, once in the morning and once in the evening, based on body weight for all subjects for all three index studies (A3921103, A3921104, and A3921165) 5 mg BID Dose Level: Body Weight (Dose in tablet [mg BID] or solution [ml BID]) 5 - < 7 kg (2 mg or 2 ml) 7 - < 10 kg (2.5 mg or 2.5 ml) 10 - <15 kg (3 mg or 3 ml) 15 - <25 kg (3.5 mg or 3.5 ml) 25 - <40 kg (4 mg or 4 ml) >=40 kg (5 mg or 5 ml) Oral solution (1 mg/mL concentration) will be used for subjects weighing <40 kg. Oral tablets (5 mg) will be used for subjects weighing >=40 kg; subjects who are unable to swallow tablets will have the option of taking oral solution. Subjects will swallow study tablets whole and will not manipulate or chew tablets prior to swallowing.<br>* Other names: CP 690,550, Xeljanz;Drug: Tofacitinib<br>* For subjects rolling over from study A3921103 and actively participating in this study at the time of Protocol Amendment 6 and receiving a dosage of tofacitinib in accordance with the dosing scheme specified in Protocol Amendment 5, investigators will have the option of maintaining the subject's current dosage regimen from index study A3921103 (if the desired clinical response has been attained with no safety concern) or adjusting the dosage regimen in accordance with the dosing scheme specified in this section.<br>* Other names: CP-690,550, Xeljanz;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standard laboratory safety data and adverse event (AE) reports. Body weight, height and Tanner Stages will collected to assess growth and physical development. |  | up to 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physician global evaluation of disease activity at each visit. |  | up to 8 years | 
| Number of joints with active arthritis at each visit. |  | up to 8 years | 
| Number of joints with limitation of motion at each visit. |  | up to 8 years | 
| Index of inflammation (C-reactive protein [CRP] and Erythrocyte Sedimentation Rate [ESR]) at each visit. |  | up to 8 years | 
| Parent's Assessment of Physical Function (Childhood Health Assessment Questionnaire [CHAQ]Disability Index)at each visit. |  | up to 8 years | 
| Parent's Assessment of Child's Arthritis Pain (Childhood Health Assessment Questionnaire [CHAQ] Discomfort Index, Visual Analog Scale [VAS])at each visit. |  | up to 8 years | 
| Parent's Global Assessment of Overall Wellbeing (Childhood Health Assessment Questionnaire [CHAQ] subsection, Visual Analog Scale [VAS])at each visit. |  | up to 8 years | 
| JIA American College of Rheumatology (ACR) response and occurrence of JIA ACR disease flare at each visit. |  | up to 8 years | 
| JIA ACR Clinical Inactive Disease status and Clinical Remission on Medication at each visit. |  | up to 8 years | 
| Change from baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27- CRP and JADAS 27-ESR, and occurrence of JADAS minimum disease activity and inactive disease at each visit. |  | up to 8 years | 
| In subjects with Enthesitis Related Arthritis (ERA): Change from baseline in the Tender Entheseal Assessment, Modified Schober's Test, Overall Back Pain and Nocturnal Back Pain responses at various visits. |  | up to 8 years | 
| In subjects with psoriatic arthritis (PsA): Change from baseline in body surface area (BSA) affected by psoriasis and Physician's Global Assessment (PGA) of psoriasis) at various visits. |  | up to 8 years | 
| In subjects with sJIA: Absence of Fever, defined as absence of fever due to sJIA in the week preceding the assessment at each visit. |  | up to 8 years | 
| Eligibility of tapering defined per protocol for corticosteroids |  | up to 8 years | 
| Eligibility of tapering defined per protocol for methotrexate |  | up to 8 years | 
| Eligibility of tapering defined per protocol for leflunomide |  | Up to 8 years | 
| Eligibility of tapering defined per protocol for tofacitinib |  | Up to 8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xeljanz, Arthritis, Pediatric, Long-term, JIA, CP-690,550, tofacitinib