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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
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.
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.
Time frame: 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).
Time frame: 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).
Time frame: From Day 1 to Day 180
Pharmacokinetics: Area Under the Concentration-Time Curve From Time 0 to 180 Days (AUC-180) of Rituximab
The AUC0-180 is a measure of the plasma concentration of rituximab over time. The AUC0-180 was calculated in micrograms per millilitres times day (mcg/mL\*day).
Time frame: From Day 1 to Day 180
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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
...and 13 more locations
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Rituximab
Cmax is the maximum observed plasma rituximab concentration. Cmax was assessed at each visit following 1st, 2nd, 3rd, and 4th IV dose of rituximab 375 mg/m\^2 on Days 1, 8, 15, and 22. Cmax was calculated in micrograms per millilitre (mcg/mL).
Time frame: From Day 1 to Day 180