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

NCT ID: NCT01750697

Last Updated: 2019-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-23
• Study Completion Date: 2018-05-10

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.

Conditions

Granulomatosis With Polyangiitis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Participants will receive rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15 and 22. Rituximab infusions will be given at a rate of 25 milligrams per hour (mg/h). This may be escalated at a rate of 25 mg/h increments every 30 minutes to a maximum of 200 mg/h.

Interventions

Rituximab

Participants will receive rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15 and 22. Rituximab infusions will be given at a rate of 25 milligrams per hour (mg/h). This may be escalated at a rate of 25 mg/h increments every 30 minutes to a maximum of 200 mg/h.

Intervention Type: DRUG

Other Intervention Names

MabThera/Rituxan

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)

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina

Rome, Lazio, Italy

University of Louisville Research Foundation, Inc; Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

COLUMBIA PRESBYTERIAN MEDICAL CENTER, Research Pharmacy, William Black Medical Research Building

New York, New York, United States

Cincinnati Childrens Hospital

Cincinnati, Ohio, United States

The Cleveland Clinic Foundation; Rheumatic and Immunologic Diseases

Cleveland, Ohio, United States

University of Utah; Immunology/Rheumatology/Allergy

Salt Lake City, Utah, United States

Alberta Children'S Hospital

Calgary, Alberta, Canada

Children's and Women's Health Center / BC Children's Hospital

Vancouver, British Columbia, Canada

The Hospital for Sick Children Research Institute

Toronto, Ontario, Canada

Hopital Femme Mere Enfant; Ped Nephrologie Rhumatologie

Bron, , France

Hop Necker Enfants Malades;UIH

Paris, , France

Universitätsklinikum für Kinder und Jugendmedizin Hamburg

Hamburg, , Germany

KfH-Nierenzentrum fur Kinder und Jugendliche

Heidelberg, , Germany

Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS

Genoa, Liguria, Italy

Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica

Padua, Veneto, Italy

Childrens University Hospital

Belgrade, , Serbia

Clinical Center Nis

Niš, , Serbia

Hacettepe University, School of Medicine; Pediatrics Department

Ankara, , Turkey (Türkiye)

Istanbul University, Cerrahpasa Medical Faculty; Pediatrics Department

Istanbul, , Turkey (Türkiye)

Alder Hey Children s Hospital; Department of Pediatrics

Liverpool, , United Kingdom

Great Ormond Street Children's Hospital; Centre of Paediatric & Adolescent Rheumatology

London, , United Kingdom

Nottingham Children's Hospital

Nottingham, , United Kingdom

Countries

United States; Canada; France; Germany; Italy; Serbia; Turkey (Türkiye); United Kingdom

References

Melega S, Brogan P, Cleary G, Hersh AO, Kasapcopur O, Rangaraj S, Yeung RSM, Zeft A, Cooper J, Pordeli P, Kirchner P, Lehane PB. Evaluation of Serious Infection in Pediatric Patients with Low Immunoglobulin Levels Receiving Rituximab for Granulomatosis with Polyangiitis or Microscopic Polyangiitis. Rheumatol Ther. 2022 Apr;9(2):721-734. doi: 10.1007/s40744-022-00433-0. Epub 2022 Mar 12.

Reference Type: DERIVED

PMID: 35279811 (View on PubMed)

Brogan P, Yeung RSM, Cleary G, Rangaraj S, Kasapcopur O, Hersh AO, Li S, Paripovic D, Schikler K, Zeft A, Bracaglia C, Eleftheriou D, Pordeli P, Melega S, Jamois C, Gaudreault J, Michalska M, Brunetta P, Cooper JC, Lehane PB; PePRS Study Group. Phase IIa Global Study Evaluating Rituximab for the Treatment of Pediatric Patients With Granulomatosis With Polyangiitis or Microscopic Polyangiitis. Arthritis Rheumatol. 2022 Jan;74(1):124-133. doi: 10.1002/art.41901. Epub 2021 Dec 5.

Reference Type: DERIVED

PMID: 34164952 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2012-002062-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WA25615

Identifier Type: -

Identifier Source: org_study_id