Study of Human Anti-TNF Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Idiopathic Arthritis (JIA)
Study of Human Anti-TNF Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Idiopathic Arthritis (JIA)
This is a multicenter, Phase 3 randomized, placebo-controlled study designed to evaluate
 adalimumab in children 4 to 17 years old with polyarticular juvenile idiopathic arthritis
 (JIA) who are either methotrexate (MTX) treated or non-MTX treated.
The study design for this clinical trial was chosen to evaluate adalimumab in subjects who
 were either methotrexate (MTX)-naive or had been withdrawn from MTX at least 2 weeks prior to
 study drug administration (non-MTX stratum) or were inadequate responders to MTX and
 continued MTX treatment (MTX stratum). The study consisted of 4 phases: a 16-week Open-label
 Lead-in (OL LI), a 32-week Double-blind (DB) phase, an up to 136-week Open-label Extension
 Body Surface Area (OLE BSA) phase, and an up to 224-week OLE Fixed Dose (FD) phase. All
 subjects who met entry criteria were enrolled into one of the appropriate strata and received
 adalimumab (plus concomitant MTX in the MTX stratum) in the 16 week OL LI phase of the study.
 All subjects who responded to adalimumab during the OL LI phase were to be enrolled in the DB
 phase of the study and randomized to receive adalimumab (plus concomitant MTX in the MTX
 stratum) or placebo (plus concomitant MTX in the MTX stratum). Subjects in the DB phase
 received either adalimumab (24 mg/m2 BSA up to a maximum of 40 mg total body dose) or placebo
 subcutaneously (SC) administered every other week (eow). Adalimumab or placebo was
 administered for an additional 32 weeks or until flare of disease (based on PedACR30 response
 criteria = a worsening of 30% or more in 3 of the 6 response variables (Parent's global
 assessment of subject's overall well-being by visual analog scale [VAS], Physician's global
 assessment [PhGA] of subject's disease severity by VAS, number of active joints [joints with
 swelling not due to deformity or joints with limitation of passive motion (LOM)], pain,
 tenderness, or both, number of joints with LOM, Childhood Health Assessment Questionnaire
 [CHAQ], and CRP levels), a minimum of 2 active joints, and no more than 1 indicator improving
 by 30% or more), whichever occurred earlier. For subjects who did not have a disease flare,
 the DB phase was completed at Week 48. Subjects who experienced disease flare during the DB
 phase or subjects who completed 48 weeks of the study were given the option to receive
 adalimumab for up to a minimum of 44 weeks (up to a maximum of 136 weeks) in the OLE BSA
 phase before being eligible to switch to the OLE FD phase. In this phase, subjects received
 OL adalimumab (24 mg/m2 BSA up to a maximum of 40 mg total body dose SC eow). All subjects
 who completed at least 44 weeks of OLE BSA treatment were given the opportunity to continue
 into the OLE FD phase for up to 224 weeks of additional adalimumab exposure. In this phase,
 subjects weighing less than 30 kg were treated with a fixed dose of 20 mg of adalimumab SC
 eow. Subjects weighing 30 kg or more were treated with a fixed dose of 40 mg of adalimumab SC
 eow.
Inclusion Criteria:

 -  Subjects must have a diagnosis of polyarticular juvenile idiopathic arthritis (JIA)
 age 4 to 17 by the American College of Rheumatology (ACR) criteria. Disease onset may
 have been systemic, polyarticular, or pauciarticular. If the disease was systemic
 onset, then the subjects must be free of any systemic JIA manifestations for at least
 3 months before the time of qualification.

 -  At the time of study screening, the subject must have continuing active disease
 defined as >= 5 swollen joints and >= 3 joints with limitation of motion (LOM). These
 joints are not mutually exclusive.

 -  Subjects may be either naïve to MTX, inadequate responders to MTX, or intolerant to
 MTX. Intolerance to MTX will be defined by the subject's physician. The MTX must be
 maintained at a dose of at least 10 mg/m2 body surface area/week for a minimum of 3
 months, prior to screening.

 -  Duration of disease is not limited, but must have been long enough for a subject to
 have been given an adequate trial of nonsteroidal anti-inflammatory drugs (NSAIDs).

 -  Have not received other disease-modifying anti-rheumatic drugs (DMARDs) including
 penicillamine, hydroxychloroquine, sulfasalazine, oral or injectable gold,
 cyclosporin; or intravenous immunoglobulin (IV Ig); or cytotoxic agents, for at least
 4 weeks prior to receiving 1st dose of study drug. Subjects currently on one or more
 of these DMARDs must demonstrate active disease (defined above) prior to a minimum 4
 weeks (28 days) washout of all DMARDs.

 -  Subjects who are refractory to MTX after 3 months of treatment must demonstrate active
 disease (defined above) prior to enrollment in the open-label part of the trial.

 -  Have not received an intra-articular glucocorticoid injection within 4 weeks (28 days)
 prior to enrollment into the study.

 -  Have good venous access and stable hematocrit >= 24%.

 -  All sexually active male and female study participants must be practicing adequate
 contraception. Post-pubertal females must have a negative serum pregnancy test no
 greater than 10 days prior to the first dose of study drug.

 -  Parent or guardian has voluntarily signed and dated an informed consent form, approved
 by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the
 nature of the study has been explained and the subject's parent or legal guardian has
 had the opportunity to ask questions.

 Exclusion Criteria:

 -  Pregnant or nursing female.

 -  Functional class IV by ACR criteria.

 -  Laboratory parameters outside limits established in the protocol.

 -  Medical history, medical condition, or previous treatment not allowed by the protocol.