E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis |
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E.1.1.1 | Medical condition in easily understood language |
ANCA-associated vasculitis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047888 |
E.1.2 | Term | Wegener's granulomatosis |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063344 |
E.1.2 | Term | Microscopic polyangiitis |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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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 |
To evaluate the safety, tolerability and pharmacokinetic parameters of rituximab in pediatric patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). |
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E.2.2 | Secondary objectives of the trial |
To explore the efficacy of rituximab for the induction of remission in pediatric patients with severe GPA or MPA; to explore the pharmacodynamics parameters of rituximab in pediatric patients with GPA or MPA |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age at screening between ≥2 and < 18 years
• Diagnosis of GPA (EULAR/PRINTO/PRES 2008, Ankara criteria for childhood WG [Özen et al. 2010]) or diagnosis of MPA (according to the Chapel Hill Consensus Conference [Jennette 1994])
• Newly diagnosed patients or patients with relapsing disease according to the following definition:
- The recurrence or new onset of potentially organ- or life-threatening disease (i.e., one or more major BVAS/WG items or disease severe enough to require treatment with cyclophosphamide).
|
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E.4 | Principal exclusion criteria |
• Diagnosis of Churg-Strauss Syndrome, as defined by the Chapel Hill Consensus Conference (Jennette 1994)
• Limited disease that would not normally be treated with cyclophosphamide
• Severe disease requiring mechanical ventilation due to alveolar hemorrhage
• Requirement for plasmapheresis or dialysis at screening
•Evidence of active tuberculosis (patients receiving chemoprophylaxis for latent tuberculosis infection are eligible for the study) |
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E.5 End points |
E.5.1 | Primary end point(s) |
- to evaluate safety and PK parameters. The primary PK parameters will be clearance and volume of distribution estimated from population PK model. The safety outcome measures are frequency, nature and severity of adverse events, and frequency of laboratory abnormalities. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PK is evaluated up to month 6. Safety is assessed throughout the trial. |
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E.5.2 | Secondary end point(s) |
- Exploratory efficacy outcomes including induction of remission,
numbers of major or minor BVAS/WG/PVAS relapses/flares, cumulative glucocorticoid dose, Exploratory pharmacodynamic outcome measures include circulating CD19-positive B cell counts. Other exploratory measures include patient reported outcomes, and vasculitis damage.
- Number of patients with disease progression prior to remission |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key time-points for exploratory efficacy evaluations include months 6, 12 and 18. |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | No |
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 |
Canada |
France |
Germany |
Italy |
Serbia |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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The end of the study will occur when the last participating patient completes the final scheduled visit (inclusive of extended follow up) or when the Sponsor decides to discontinue the study or development program. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |