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

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Brief Title

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

Official Title

A Phase IIA, International, Multicenter, Open-label, Uncontrolled Study to Evaluate The Safety And Pharmacokinetics of 4 × 375 mg/m2 Intravenous Rituximab in Pediatric Patients With Severe Granulomatosis With Polyangiitis (Wegener's) or Microscopic Polyangiitis

Brief Summary

      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.
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Percentage of Participants With Adverse Events (AEs), Including Serious AEs

Secondary Outcome

 Pharmacokinetics: Area Under the Concentration-Time Curve From Time 0 to 180 Days (AUC-180) of Rituximab

Condition

Granulomatosis With Polyangiitis

Intervention

Rituximab

Study Arms / Comparison Groups

 Rituximab
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

25

Start Date

May 23, 2013

Completion Date

May 10, 2018

Primary Completion Date

May 10, 2018

Eligibility Criteria

        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)
      

Gender

All

Ages

2 Years - 17 Years

Accepts Healthy Volunteers

No

Contacts

Clinical Trials, , 

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT01750697

Organization ID

WA25615

Secondary IDs

2012-002062-13

Responsible Party

Sponsor

Study Sponsor

Hoffmann-La Roche


Study Sponsor

Clinical Trials, Study Director, Hoffmann-La Roche


Verification Date

June 2019