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

NCT01750697 | Completed Phase 2 Results

• 2 other identifiers: WA256152012-002062-13
• Study Type: interventional
• Target: 25
• Locations: 8 countries
• Sites: 23

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

Outcome Measures

Primary Outcomes (3)

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

  An AE is any unfavourable and unintended sign (including abnormal laboratory finding), symptom, or disease temporarily associated with the use of a study drug, whether or not considered related to the study drug. A SAE is any experience that results in death, is life-threatening, requires in-patient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant.

  Baseline (Day 1) up to last visit (1.5-5 years)

• Pharmacokinetics: Rituximab Clearance (CL)

  CL is a quantitative measure of the rate at which a drug substance is removed from the body. The following allometric scaling equation was used for the estimation of CL in children: CL= qCL X (BSA/1.9) 0.92 X 1.31\*ADA where qCL is a typical value of clearance in millilitres per day (mL/day) for a typical participant (i.e., Body Surface Area (BSA) of 1.9 m\^2 and absence of anti-rituximab antibodies (ADA)) and is equal to 258 mL/day; BSA is in m\^2 and ADA is 1 when anti-rituximab antibodies are present (0 otherwise). The allometric scaling factor was 0.92. CL was calculated in millilitres per day (mL/day).

  From Day 1 to Day 180

• Pharmacokinetics: Volume of Distribution (Vd) of Rituximab

  Vd is defined as the theoretical central volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vd was calculated in millilitres (mL).

  From Day 1 to Day 180

Secondary Outcomes (2)

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

  From Day 1 to Day 180

• Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Rituximab

  From Day 1 to Day 180

Study Arms (1)

Rituximab

EXPERIMENTAL

Drug: Rituximab

Interventions

Rituximab 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.

Also known as: MabThera/Rituxan

Rituximab

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (23)

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

Louisville, Kentucky, 40202, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

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

New York, New York, 10032, United States

Location

Cincinnati Childrens Hospital

Cincinnati, Ohio, 45229, United States

Location

The Cleveland Clinic Foundation; Rheumatic and Immunologic Diseases

Cleveland, Ohio, 44195, United States

Location

University of Utah; Immunology/Rheumatology/Allergy

Salt Lake City, Utah, 84109, United States

Location

Alberta Children'S Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

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

Vancouver, British Columbia, V6H 3V4, Canada

Location

The Hospital for Sick Children Research Institute

Toronto, Ontario, M5G 1L7, Canada

Location

Hopital Femme Mere Enfant; Ped Nephrologie Rhumatologie

Bron, 69677, France

Location

Hop Necker Enfants Malades;UIH

Paris, 75743, France

Location

Universitätsklinikum für Kinder und Jugendmedizin Hamburg

Hamburg, 20246, Germany

Location

KfH-Nierenzentrum fur Kinder und Jugendliche

Heidelberg, 69120, Germany

Location

Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina

Rome, Lazio, 00165, Italy

Location

Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS

Genoa, Liguria, 16147, Italy

Location

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

Padua, Veneto, 35128, Italy

Location

Childrens University Hospital

Belgrade, 11000, Serbia

Location

Clinical Center Nis

Niš, 18000, Serbia

Location

Hacettepe University, School of Medicine; Pediatrics Department

Ankara, 06100, Turkey (Türkiye)

Location

Istanbul University, Cerrahpasa Medical Faculty; Pediatrics Department

Istanbul, 34098, Turkey (Türkiye)

Location

Alder Hey Children s Hospital; Department of Pediatrics

Liverpool, L12 2AP, United Kingdom

Location

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

London, WC1N 1EH, United Kingdom

Location

Nottingham Children's Hospital

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 35279811 DERIVED

• 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.

  PMID: 34164952 DERIVED

MeSH Terms

Conditions

Granulomatosis with Polyangiitis

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

After Month 6, participants could receive treatment for GPA/MPA in accordance with local standard of care, and this could include additional rituximab infusions and/or other immunosuppressive therapies. Low participant numbers (e.g., 1 subject = 4%).

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2012
• First Posted: December 17, 2012
• Study Start: May 23, 2013
• Primary Completion: May 10, 2018
• Study Completion: May 10, 2018
• Last Updated: June 26, 2019
• Results First Posted: June 26, 2019

Record last verified: 2019-06

Locations

CA (3); FR (2); DE (2); US (6); IT (3); GB (3); TU (2); SE (2)