Systemic juvenile idiopathic arthritis (sJIA) MedDRA version: 21.0 Level: PT Classification code 10059176 Term: Juvenile idiopathic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1 and Part 2: • Age 2 years up to and including 17 years at screening into trial • sJIA according to International League of Associations for Rheumatology (ILAR) classification (2001) • sJIA symptoms lasting for at least 1 month since diagnosis of sJIA • For female patients of reproductive potential: agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of 1 to 3 xULN TCZ=tocilizumab; ULN=upper limit of normal. • Not currently receiving oral corticosteroids, or taking oral corticosteroids at a stable dose for a minimum of 2 weeks prior to the part 2 baseline visit at no more than 10 mg/day or 0.2 mg/kg/day, whichever is less. • Not taking NSAIDs, or taking no more than 1 type of NSAID at a stable dose for a minimum of 2 weeks prior to the part 2 baseline visit, with the dose being less than or equal to the maximum recommended daily dose. Are the trial subjects under 18? yes
Exclusion criteria
Exclusion criteria: • Wheelchair bound or bedridden • Lack of peripheral venous access. • Any other auto-immune, rheumatic disease, or overlap syndrome other than sJIA. •Not fully recovered from recent surgery or less than 6 weeks since surgery, at the time of screening visit; or planned surgery during Part 1 and the initial 12 weeks of Part 2 of the study (for patients entering Part 1) or the initial 12 weeks of Part 2 of the study (for patients entering Part 2 without participating in Part 1). • Any significant concurrent medical or surgical condition which would jeopardize the patient's safety or ability to complete the trial. • Pregnant, lactating, or intending to become pregnant during study conduct and up to 6 months after the last administration of study drug. • History of significant allergic or infusion reactions to prior TCZ infusion, and/or presence of anti-TCZ antibodies by confirmatory and/or neutralizing assay at screening. • Inborn conditions characterized by a compromised immune system. • Known HIV infection or other acquired forms of immune compromise. • History of alcohol, drug, or chemical abuse within 6 months of screening. • Evidence of serious uncontrolled concomitant diseases, including but not limited to the nervous, renal, hepatic, or endocrine systems. • Any active acute, subacute, chronic, or recurrent bacterial, viral, or systemic fungal infection including but not limited to: a) Acute or chronic renal / bladder infections b) Acute or chronic pulmonary infections • History of atypical tuberculosis (TB) • Active TB requiring treatment within 2 years prior to the screening visit • Positive purified protein derivative (PPD) at screen (or equivalent result based on local methodology, e.g., Quantiferon gold), unless treated with anti-TB therapy for at least 4 weeks prior to receiving study drug and chest radiograph is negative for active TB within 6 months of screening visit according to local practice • Any major episode of infection requiring hospitalization or treatment during screening or treatment with IV antibiotics completing within 4 weeks of the screening visit or oral antibiotics completing within 2 weeks of the screening visit • History of reactivation or new onset of a systemic infection, such as herpes zoster or Epstein Barr virus, within 2 months of the screening visit • Hepatitis B surface Antigen or hepatitis C Ab positive • Chronic hepatitis - viral or autoimmune • History or concurrent serious gastrointestinal (GI) disorders, such as ulcer or inflammatory bowel disease, Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions, including ulcer and perforation • Significant cardiac [e.g., congenital heart disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy: • To explore the efficacy of TCZ in reduced dosing frequency regimens (Q3W and Q4W, as appropriate) using Juvenile Arthritis Disease Activity Score (JADAS)-71, JIA flare, and fever (attributable to sJIA) Pharmacodynamic: • To describe the pharmacodynamics, using sIL-6R and C-reactive protein (CRP), and immunogenicity of TCZ in reduced dosing frequency regimens. ; Secondary Objective: Safety: • To evaluate the safety of TCZ in reduced dosing frequency regimens. Pharmacokinetic: • To describe the pharmacokinetics of TCZ in reduced dosing frequency regimens. Patient-Reported Outcome: • To describe the Child Health Assessment Questionnaire (CHAQ) outcomes with TCZ in reduced dosing frequency regimens. • To describe parent/patient global assessment of overall well-being with TCZ in reduced dosing frequency regimens. ; Primary end point(s): Efficacy: 1.JADAS-71 will be utilized to describe efficacy in patients on Q3W and Q4W dosing as appropriate in this study 2.JIA flare relative to baseline of Part 2 will be used to determine those patients not maintaining efficacy who can be withdrawn from the study at the discretion of the investigator 3.Fever (attributable to sJIA) will be measured at each study visit of Part 2 in patients on Q3W and Q4W dosing (as appropriate) to describe efficacy and to determine patients not maintaining efficacy who can be withdrawn from the study at the discretion of the investigator Pharmocokinetics and Pharmacodynamic: 4.Serum IL-6 and sIL-6R levels and inflammatory markers (CRP and erythrocyte sedimentation rate [ESR]) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Part 1: week 1 up to 24 weeks for safety Part 2: Q3W up to 12 weeks or 52 weeks; Q4W 12 weeks up to 52 weeks for safety, PRO and pharmacokinetics ; Secondary end point(s): Safety: • Adverse events (including adverse events of special interest) • Serious adverse events • Clinical laboratory results Pharmacokinetic: • Serum TCZ concentration and population PK model predicted PK exposures (area under the serum concentration-time profile [AUCt], maximum concentration observed [Cmax], and minimum concentration under steady-state conditions within a dosing interval [Cmin]) for Q3W and Q4W dosing regimens as appropriate Patient-Reported Outcome: • The CHAQ • Parents/patients global assessment of overall well-being | — |
Countries
Australia, Canada, Germany, Israel, Italy, Mexico, Norway, Russian Federation, Spain, Sweden, United Kingdom
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed