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

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.

This study (A3921145) is planned to run until the first global marketing approval of tofacitinib for the treatment of JIA. The total duration of an individual subject's participation may vary depending upon when they enter the trial.

• Drug: Tofacitinib
  

  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.

  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.

  Other Name: CP 690,550, Xeljanz
• Drug: Tofacitinib
  
  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.
  Other Name: CP-690,550, Xeljanz
• Drug: Tofacitinib
  

  For participants rolling over from study A3921165: 10 mg BID Dose Level

  Body Weight (Dose in tablet [mg BID] or solution [ml BID])

  5 ? < 7 kg (4 mg or 4 ml) 7 - < 10 kg (5 mg or 5 ml) 10 - <15 kg (6 mg or 6 ml) 15 - <25 kg (7 mg or 7 ml) 25 - <40 kg (8 mg or 8 ml) >=40 kg (10 mg or 10 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.

  Other Name: CP 690,550; Xeljanz

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:

• Systemic JIA (sJIA) with active systemic features other than active joints and elevated acute phase reactants, persistent oligoarthritis, and undifferentiated JIA.

• Infections:

  1. Chronic infections.
  2. Any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within the 6 months prior to the first dose of study drug.
  3. Any treated infections within 2 weeks of baseline visit.
  4. A subject known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus.
  5. 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.