A phase IIa, international, multicenter, open-label, uncontrolled study to evaluate the safety and pharmacokinetics of 4 x 375 mg/m2 Intravenous rituximab in pediatric patients with severe granulomatosis with polyangiitis (Wegener’s) or microscopic polyangiitis

Phase 1

• Conditions: granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis; MedDRA version: 19.0Level: LLTClassification code 10047888Term: Wegener's granulomatosisSystem Organ Class: 10047065 - Vascular disorders; MedDRA version: 19.0Level: PTClassification code 10063344Term: Microscopic polyangiitisSystem Organ Class: 10047065 - Vascular disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2012-002062-13-GB
• Lead Sponsor: F. Hoffmann-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-08-23
• Study Completion: 2018-05-10
• Last Update Posted: 20 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

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).

Are the trial subjects under 18? yes
Number of subjects for this age range: 25
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.;Timepoint(s) of evaluation of this end point: PK is evaluated up to month 6. Safety is assessed throughout the trial.;Main Objective: To evaluate the safety, tolerability and pharmacokinetic parameters of rituximab in pediatric patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).;Secondary Objective: 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

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Exploratory efficacy outcomes including induction of remission,<br>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.<br>- Number of patients with disease progression prior to remission ;Timepoint(s) of evaluation of this end point: Key time-points for exploratory efficacy evaluations include months 6, 12 and 18.