Efficacy and Safety Study Of Tofacitinib in Pediatric sJIA Populatio

Phase 1

Conditions: Systemic Juvenile Idiopathic Arthritis (sJIA)
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2017-002018-29-BE

Lead Sponsor: Pfizer Inc. 235 East 42nd Street, New York, New York 10017

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 100

Inclusion Criteria

1.Male or female aged 2 to <18 years.
2.Diagnosed with sJIA according to International League Against Rheumatism (ILAR) criteria, and, in the opinion of the inv., have active disease prior to screening. Subjects with first-degree relatives with history of psoriasis, ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, Reiter’s syndrome, or acute anterior uveitis may be allowed for enrollment after consultation with the sponsor. Subjects must have active disease at the time of enrollment defined as:
a.Documented intermittently spiking temperature >38°C/100.4°F 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: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 3.4 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 4 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 Gold Plus In Tube test performed within the 3 months prior to screening. A negative
QuantiFERON®-TB test performed locally or 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.
Note: If a subject has previously received an adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi drug resistant TB infection are <5% or an acceptable alternative regimen) or active (acceptable multi drug regimen) TB infection, neither a PPD test nor a QuantiFERON® TB Gold or Gold Plus test need be obtained. A chest radiograph ray be obtained to aid in TB status determination, according to local standards and/or in countries with a high incidence rate of TB (see 7.2.7).To be considered eligible for the study, the chest radiograph must be negative for active tuberculosis infection.
A subject who is currently being treated for latent TB infection can only be enrolled with confirmation of current incidence rates of multi drug resistant TB infection, documentation of an adequate treatment regimen, and

Exclusion Criteria

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
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);
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):
a.Hemoglobin <9 g/dL;
b.White Blood Cell count <3.0 x 109/L;
c.Absolute Neutrophil count <1.2 x 109/L;
d.Platelet count <100 x 109/L;
e.Absolute Lymphocyte count <0.75 x 109/L.
9.Estimated glomerular filtration rate [eGFR] <40 mL/min/1.73 m2 at Screening. eGFR will be calculated by the central lab using the bedside Schwartz formula (see Appendix 4).
10.Current or recent history of uncontrolled clinically significant renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
11.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =1.5 times the upper limit of normal or any other clinically significant laboratory abnormality (see Appendix 7).
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 vaccine within the 6 weeks prior to the first dose of study drug, or is expected to be vaccinated or to have household exposure to these vaccines 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.
19.Prior treatment with non B cell specific lymphocyte depleting agents/therapies (eg, alemtuzumab [CAMPATH®], alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc.).Subjects who have received rituximab or other selective B lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to study baseline and have normal CD 19/20+ counts by FACS analysis.
20.Use of prohibited prescription or non prescription drugs and dietary s