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

Phase 3

Withdrawn

Conditions: juvenile rheumatoid arthritis
Still's disease
10003816
10023213

Registration Number: NL-OMON51984

Lead Sponsor: Syneos Health Netherlands B.V

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 2

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 investigator, prior to screening.
Subjects with first-degree relatives with history of psoriasis, ankylosing
spondylitis, enthesis-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 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

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 < 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 [GFR] < 40 mL/min/1.73 m2 at Screening.
GFR will be calculated by the central lab using the bedside Schwartz formula
(see Appendix 4 of the protocol).
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 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