E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Juvenile Idiopathic Arthritis (sJIA) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059177 |
E.1.2 | Term | Juvenile arthritis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part I: Primary Objectives: 1. To assess the efficacy of tocilizumab versus placebo in combination with stable ongoing therapy at 12 weeks, with regard to signs and symptoms in sJIA patients with persistent activity and an inadequate response to NSAIDs and systemic corticosteroids. 2. To evaluate the short term safety of tocilizumab versus placebo in combination with stable ongoing therapy at 12 weeks, with regard to adverse events and laboratory assessments in patients with sJIA with persistent activity and an inadequate response to NSAIDs and corticosteroids. Part II: Primary Objectives: 1. To evaluate the safety of tocilizumab in chronic administration; 2. To assess the effect of tocilizumab to enable the reduction or elimination of corticosteroids. |
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E.2.2 | Secondary objectives of the trial |
Part I: Secondary Objectives: 1. To assess the efficacy of tocilizumab versus placebo in combination with stable ongoing therapy, with regard to common systemic features in sJIA patients with persistent activity and an inadequate response to NSAIDs and corticosteroids; 2. To assess the efficacy of treatment with tocilizumab to permit concomitant corticosteroid reduction; 3. To explore the immunogenicity and pharmacodynamic properties of tocilizumab in this patient population; 4. To investigate, by a population analysis approach, the pharmacokinetics of tocilizumab in sJIA patients, including the influence of covariates. Part II: Secondary Objectives: 1. To assess the durability and magnitude of the tocilizumab efficacy response in patients with sJIA including meeting the definition of inactive disease and clinical remission. 2. To assess the efficacy of treatment with tocilizumab to permit concomitant medication reductions. Etc. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALTRI SOTTOSTUDI: Progetto di ricerca Roche per la raccolta di campioni per la determinazione dei marcatori biologici.
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E.3 | Principal inclusion criteria |
1. Age 2 up to and including 17 years at screening into trial; 2. Systemic Juvenile Idiopathic Arthritis according to ILAR classification (2001); 3. More than 6 months of persistent sJIA activity prior to screening including an inadequate response to NSAIDs and corticosteroids due to toxicity or lack of efficacy. 4. Presence of active disease as determined by the presence of : > 5 active joints, or > 2 active joints and fever >38C for at least 5 out of any 14 consecutive days during screening and receiving prednisone or equivalent at a stable dose at nomore than 0.5 mg/kg/day or 30 mg/day, whichever is less. During this same time period the corticosteroid dose continues unchanged. 5. hsCRP > 4.3 mg/L or 0.43 mg/dl (1.5 x ULN (ULN= 0.28 mg/dl)); 6. Recovered from any symptomatic serositis for at least one month prior to the screening visit, and requiring dose of corticosteroids < than 30 mg/day at baseline 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]. Etc. |
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E.4 | Principal exclusion criteria |
General Exclusion Criteria 1. Wheelchair or bedridden; 2. Any other auto-immune, rheumatic disease or overlap syndrome other than sJIA; 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 12 weeks of the study; 4. Lack of peripheral venous access; Other Exclusion criteria regarding - General Safety - Previous or Concomitant Therapy - Laboratory Exclusions |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: The proportion of patients with at least 30% improvement in JIA core set (JIA ACR30 response) at week 12 (JIA Core Set assessed in comparison to baseline) and absence of fever* *Absence of fever is defined as no temperature measurement > 37.5 C. in the preceding seven days |
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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 | Yes |
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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
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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
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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 | 0 |
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 | 0 |