juvenile rheumatoid arthritis Still's disease
Conditions
Interventions
Open-label phase: All subjects
Sponsors
Syneos Health Netherlands B.V
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: 1.Male or female aged 2 to 38*C for at least 1 day due to sJIA in the screening period and within 1 week before the first dose, and the presence of at least 2 joints with active arthritis at screening and baseline, and an ESR >30 mm/hr [1.5 X ULN] at screening. OR b.Only after cohort review is completed and enrollment is opened without restrictions at a particular dose level: The presence of at least 5 joints with active arthritis at screening and baseline, and an ESR >30 mm/hr [1.5 X ULN] at screening. Refer to Section 3.4 of the protocol for details. 3.Treatment with stable doses of methotrexate (MTX) and/or oral CSs is permitted: •For subjects taking MTX: Treatment for >=3 months with MTX and with a stable dose of MTX (dose must be <=25 mg/wk or <=20 mg/m2/week, whichever is lower) for at least 46 weeks before the first study drug dose (Day 1). Subjects taking MTX must be taking folic acid or folinic acid in accordance with local standards. •For subjects taking CS: 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 (Day 1). 4.No evidence or history of untreated or inadequately treated active or latent tuberculosis (TB) infection as evidenced by the following: •A negative QuantiFERON® TB Gold or Glod Plus In Tube test performed within the 3 months prior to screening. A negative purified protein derivative (PPD) test can be substituted for the QuantiFERON® TB Gold or Gold Plus In Tube test only if the central laboratory is unable to perform the test or cannot determine the results to be positive or negative and the Pfizer medical monitor is informed and agrees on a case by case basis. •Chest radiograph without changes suggestive of active tuberculosis (TB) infection within 3 months prior to screening is recommended and should be performed according to local standards of care or country specific guidelines. •No history of either untreated or inadequately treated latent or active TB infection. 5.Fertile males and females who are, in the opinion of the investigator, sexually active and at risk for pregnancy with their partner(s) must be willing and able to use a highly effective method of contraception as outlined in this protocol during the study and for at least 28 days after the last dose of study medication (see Section 4.4.1 of the protocol). Country-specific amendment for EU sites (including UK): Subjects who are, in the opinion of the investigator, sexually active and at risk for pregnancy with their partner(s) must agree to use 2 methods of contraception (at least one of which is considered to be highly effective with low user dependency as defined below) throughout the study and for
Exclusion criteria
Exclusion criteria: Subjects with any of the following characteristics/conditions will not be included in the study: 1.Previous JIA treatment with tofacitinib. 2.Current symptoms or findings of myocarditis, endocarditis or more than minimal pericardial effusion associated with sJIA. 3.Current symptoms or findings of more than minimal pleuritis with sJIA. 4.Subjects who are still within the washout periods for disallowed nonbiological and biological DMARDs as indicated in Section 5.8.1.2 of the protocol. 5.Infections: a.Chronic infections; b.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; c.Any treated infections within 2 weeks of baseline; d.A subject known to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C (see Section 7.2.8 of the protocol); e.History of infected joint prosthesis with prosthesis still in situ. 6.History of recurrent (more than one episode) herpes zoster or disseminated (at least one episode) herpes zoster, or disseminated (at least one episode) herpes simplex. 7.Diagnosis of active Macrophage Activation Syndrome (MAS) within 3 months prior to the first dose of study drug. 8.Blood dyscrasias, including (see Appendix 7 of the protocol): a.Hemoglobin =1.5 times the upper limit of normal or any other clinically significant laboratory abnormality (see Appendix 7 of the protocol). 12.History of any other rheumatologic disease, other than Sjogren*s syndrome. 13.History or current symptoms suggestive of lymphoproliferative disorders (eg, Epstein Barr Virus [EBV] related lymphoproliferative disorder, lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease). 14.Vaccinated or exposed to a live or attenuated vaccine within the 6 weeks prior to the first dose of study drug, or is expected to be vaccinated or there are household members that require oral polio vaccination (see Section 4.5.2 Vaccination in Household Members) during treatment or during the 6 weeks following discontinuation of study drug. 15.Current malignancy or history of any malignancy with the exception of adequately treated or excised basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ. 16.Subjects with a first degree relative with a hereditary immunodeficiency; IgA deficiency not exclusionary. 17.Recent (within 28 days prior to first dose of study drug) significant trauma or major surgery. 18.Subjects receiving potent and moderate CYP3A4 inhibitors or inducers (Appendix 5 of the protocol). 19.Prior treatment with non B cell specific lymphocyte depleting agents/thera
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * Time to sJIA disease flare in the double-blind randomized withdrawal phase. | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy endpoints: * Occurrence of disease flares in the double-blind phase at each visit. * Achievement of corticosteroid tapering per protocol at the end of the open-label active treatment period in applicable subjects receiving corticosteroids on study Day 1 of the open-label phase. * Achievement of a corticosteroid dose of 38 Degrees Celsius) attributed to sJIA at Day 3, Day 7 and Day 14 of the open-label phase. * CRP | — |
Countries
Netherlands
Outcome results
None listed