A Phase IIa Study of Intravenous Rituximab in Pediatric Participants With Severe Granulomatosis With Polyangiitis (Wegener's) or Microscopic Polyangiitis

Roche

Status and phase

Completed

Phase 2

Conditions

Granulomatosis With Polyangiitis

Treatments

Drug: Rituximab

Study type

Interventional

Funder types

Industry

Identifiers

NCT01750697

WA25615

2012-002062-13 (EudraCT Number)

Details and patient eligibility

About

This Phase IIa international multicenter, open-label, uncontrolled study will evaluate the safety and pharmacokinetics of rituximab (MabThera/Rituxan) in pediatric participants with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Participants will receive rituximab 375 milligrams per square meter (mg/m^2) intravenously (IV) on Days 1, 8, 15 and 22.

Enrollment

25 patients

Sex

All

Ages

2 to 17 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosis of GPA (EULAR/PRINTO/PRES 2008, Ankara criteria for childhood Wegener's granulomatosis) or diagnosis of MPA (according to the Chapel Hill Consensus Conference)
Newly diagnosed participants or participants 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 Birmingham Vasculitis Activity Score for Wegener's Granulomatosis [BVAS/WG] items or disease severe enough to require treatment with cyclophosphamide)

For participants of reproductive potential (males and females), use of reliable means of contraception throughout the study participation
For all eligible participants mandatory prophylactic treatment for Pneumocystis jirovecii infection

Exclusion criteria

Diagnosis of Churg-Strauss syndrome, as defined by the Chapel Hill Consensus Conference
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
Incomplete recovery from recent surgery or less than (<) 12 weeks since surgery prior to baseline or planned within 24 weeks of baseline
Lack of peripheral venous access
Pregnancy or breast-feeding
Evidence of other significant uncontrolled concomitant disease, or of disorder or condition that, in the investigator's opinion, would preclude or interfere with participation of participant
Primary or secondary immunodeficiency (history of or currently active), including known history of human immunodeficiency virus (HIV) infection
Evidence of active tuberculosis (participants receiving chemoprophylaxis for latent tuberculosis infection are eligible for the study)
Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV anti-infective agents within 4 weeks of baseline or completion of oral anti-infective agents within 2 weeks prior to baseline. Entry into this study may be reconsidered once the infection has fully resolved
History of deep space/tissue infection within 24 weeks prior to baseline
History of serious recurrent or chronic infection
History of cancer (except for basal cell and squamous cell carcinoma of the skin that have been excised and cured)
Currently active alcohol or drug abuse or history of alcohol or drug abuse
History of severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of rituximab or to murine proteins
Treatment with rituximab or other biologic B cell-targeted therapy (e.g., anti- Cluster of Differentiation [CD] 19, anti-CD20, anti-CD22, or anti-B-lymphocyte stimulator [BLys]/B-cell activating factor [BAFF]) within 6 months prior to baseline visit
Previous treatment with an anti-alpha 4 integrin antibody or co-stimulation modulator
Previous treatment with other cell-depleting therapies, including, but not limited to, investigational agents (e.g., alemtuzumab, anti-CD4, anti-CD5, anti-CD3, and anti-CD11a)
Receipt of oral or IV cyclophosphamide within the previous 4 months prior to the baseline visit
Receipt of infliximab within 3 months, adalimumab within 2 months or etanercept within 1 month prior to the baseline visit
Treatment with any investigational agent within 28 days of baseline or 5 half-lives of the investigational drug (whichever is longer)
Receipt of any live attenuated vaccine within 28 days prior to baseline
Intolerance or contraindications to IV glucocorticoids
Positive serum human chorionic gonadotropin measured at screening or a positive pregnancy test prior to the first rituximab infusion for participants of childbearing potential
Positive tests for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis B virus (HBV), or hepatitis C serology
Level of Immunoglobulin (Ig) M below lower limit of normal of age-specific reference range
Level of IgG below 5.65 milligram per milliliter
Absolute neutrophil count < 1.5 × 10^3 per microliter and platelet count < 130 × 10^3 per microliter
Estimated Glomerular Filtration Rate < 15 milliliter per minute per 1.73 m^2
Alanine aminotransferase or aspartate aminotransferase levels greater than 2.5 times the upper limit of normal (for age and sex) that cannot be attributed to underlying granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)