| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Polyarticular-course JIA (pcJIA) consisting of RF-positive, RF-negative, and extended oligoarticular subsets. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10059176 |
| E.1.2 | Term | Juvenile idiopathic arthritis |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Primary Objective (from PART II): To compare the proportion of patients on tocilizumab versus placebo who develop a JIA ACR30 flare (compared to week 16) by week 40. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the efficacy of open-label tocilizumab therapy (Part I). To evaluate the long-term effect of tocilizumab on the maintenance of clinical response and safety in patients with pcJIA (Part III). To evaluate the efficacy and safety of 8 mg/kg vs 10 mg/kg in patients < 30 kg (Parts I, II and III). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Documented evidence of polyarticular-course juvenile idiopathic arthritis (pcJIA): Rheumatoid Factor Positive or Rheumatoid Factor Negative JIA polyarthritis subset (pJIA) for at least 6 months -or - extended oligoarticular JIA (eoJIA) with active polyarticular course for at least 6 months prior to study entry according to ILAR Criteria [8] 2. Polyarticular-course JIA requiring presence of active disease with at least five joints with active arthritis (joints that are swollen or if no swelling is present limitation of movement accompanied by pain tenderness or both) at both screening and baseline (with a least three of the active joints having limitation of motion). 3. Age 2 years up to and including age 17 years at the time of enrollment 4. Must meet one of the following: Have had an inadequate response to MTX or Inability to tolerate MTX 5. Must meet one of the following: not receiving MTX for at least 4 weeks prior to baseline visit, -or- taking MTX for at least 12 weeks immediately prior to the baseline visit and on a stable dose of &#8805;10 to &#8804;20 mg/m2 for at least 8 weeks prior to the baseline visit, together with either folic acid or folinic acid. 6. Must meet one of the following: Not currently receiving oral corticosteroids �or- taking oral corticosteroids at a stable dose for a minimum of 4 weeks prior to the baseline visit at no more than 10 mg/day or 0.2 mg/kg/day whichever is less; 7. Fertility: Female not of child-bearing potential, or Female of child-bearing potential practicing effective contraceptive measures, having a negative urine pregnancy test within three weeks prior to randomization; or Sterile male, or Non sterile male practicing effective contraceptive measures with female partner of child-bearing potential. [Females of childbearing potential must be using a reliable means of contraception (abstinence being a possible option) throughout the study and up to 12 weeks after the last infusion of study drug]. 8. Must meet one of the following: 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 baseline visit and is less than or equal to the maximum recommended daily dose; 9. Must meet one of the following Never treated with biologics �or-, If previously treated must have discontinued anakinra &#8805; 1 week prior to baseline, etanercept &#8805; 2 weeks prior to baseline, rilonacept &#8805; 5 weeks prior to baseline, infliximab or adalimumab &#8805; 8 weeks prior to baseline, abatacept &#8805; 12 weeks prior to baseline or canakinumab &#8805; 20 weeks prior to baseline. 10. Written informed consent for study participation obtained from parents or legal guardian, with assent as appropriate by the patient, depending on the level of the patient�s understanding. |
|
| E.4 | Principal exclusion criteria |
| The presence of any of the following will exclude the patient. General: 1. Wheelchair bound or bedridden or has little or no ability for self-care; 2. Any other auto-immune, rheumatic disease or overlap syndrome other than the permitted polyarticular-course JIA subsets; Rheumatoid Factor Positive polyarticular JIA, Rheumatoid Factor Negative polyarticular JIA, and extended oligoarticular JIA. The excluded illnesses include but are not limited to systemic juvenile idiopathic arthritis, Lyme disease, enthesitis-related arthritis; psoriatic arthritis, Reiter�s syndrome, systemic lupus erythematosus, infectious or reactive arthritis or parvovirus infections (See Appendix 1 for definitions); 3. Not fully recovered from recent surgery or less than six weeks since surgery, at the time of screening visit; or planned surgery during the initial 40 weeks of the study; 4. Lack of peripheral venous access or unwilling to undergo multiple venipunctures. General Safety: 1. Pregnant, lactating, or intending to become pregnant during study conduct and up to 12 weeks after the last administration of study drug; 2.Any significant concurrent medical or surgical condition which would jeopardize the patient�s safety or ability to complete the trial; 3. History of significant allergic or infusion reactions to prior biologic therapy; 4. History of or currently active primary or secondary immunodeficiency 5. History of alcohol, drug or chemical abuse within 1 year of screening; 6. Evidence of serious uncontrolled concomitant diseases including but not limited to the cardiovascular, pulmonary, nervous, renal, hepatic or endocrine system; 7. Any active acute, subacute, chronic or recurrent bacterial, mycobacterial, viral or systemic fungal infection or opportunistic infection; 8. Active TB requiring treatment within 2 years prior to screening visit or currently active TB; 9. Positive PPD at screen unless chest radiograph is negative for active tuberculosis at screen and patient treated with anti-tuberculosis therapy for at least 4 weeks prior to receiving study medication; 10. Any major episode of infection requiring hospitalization or treatment during screening or treatment with IV antibiotics completed within 4 weeks of the screening visit or oral antibiotics completed within 2 weeks of the screening visit; 11. Known active current or history of recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infections, (e.g. bronchiectasis, ), an open or draining or infected skin wound, sinusitis, recurrent urinary tract infection (e.g. recurrent pyelonephritis); 12. 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; 13. Hepatitis B surface Ag or hepatitis C Ab positive; 14. Chronic hepatitis; 15. Significant cardiac [e.g. congenital heart disease, valvular heart disease, constrictive pericarditis, myocarditis] or pulmonary disease, (e.g. asthma, cystic fibrosis) ; Et al... |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Part II. Proportion of patients who develop a JIA ACR30 flare (relative to week 16) in the period from week 16 up to and including week 40. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Immunogenicita`, valutazione qualita` della vita |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| LPLV programmata della parte III, o decisione Sponsor di interrompere lo sviluppo farmaco.Se a fine studio tocilizumab non fosse in commpercio per il trattamento della pcJIA , si adotteranno le misure necessarie per fornire il farmaco ai pazienti. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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