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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01750697
• Collaborator: (none)
• Enrollment: 25
• Locations: 23
• Arm: 1
• Actual Duration (Months): 59.6
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Granulomatosis With Polyangiitis	Drug: Rituximab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 23, 2013
• Actual Primary Completion Date: May 10, 2018
• Actual Study Completion Date: May 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rituximab	Drug: 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.; Other Names: MabThera/Rituxan

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Events (AEs), Including Serious AEs [Baseline (Day 1) up to last visit (1.5-5 years)]

   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.

2. Pharmacokinetics: Rituximab Clearance (CL) [From Day 1 to Day 180]

   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).

3. Pharmacokinetics: Volume of Distribution (Vd) of Rituximab [From Day 1 to Day 180]

   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).

Secondary Outcome Measures

1. Pharmacokinetics: Area Under the Concentration-Time Curve From Time 0 to 180 Days (AUC-180) of Rituximab [From Day 1 to Day 180]

   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).

2. Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Rituximab [From Day 1 to Day 180]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Louisville Research Foundation, Inc; Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky	United States	40202
2	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
3	COLUMBIA PRESBYTERIAN MEDICAL CENTER, Research Pharmacy, William Black Medical Research Building	New York	New York	United States	10032
4	Cincinnati Childrens Hospital	Cincinnati	Ohio	United States	45229
5	The Cleveland Clinic Foundation; Rheumatic and Immunologic Diseases	Cleveland	Ohio	United States	44195
6	University of Utah; Immunology/Rheumatology/Allergy	Salt Lake City	Utah	United States	84109
7	Alberta Children'S Hospital	Calgary	Alberta	Canada	T3B 6A8
8	Children's and Women's Health Center / BC Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
9	The Hospital for Sick Children Research Institute	Toronto	Ontario	Canada	M5G 1L7
10	Hopital Femme Mere Enfant; Ped Nephrologie Rhumatologie	Bron		France	69677
11	Hop Necker Enfants Malades;UIH	Paris		France	75743
12	Universitätsklinikum für Kinder und Jugendmedizin Hamburg	Hamburg		Germany	20246
13	KfH-Nierenzentrum fur Kinder und Jugendliche	Heidelberg		Germany	69120
14	Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina	Roma	Lazio	Italy	00165
15	Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS	Genova	Liguria	Italy	16147
16	Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica	Padova	Veneto	Italy	35128
17	Childrens University Hospital	Belgrade		Serbia	11000
18	Clinical Center Nis	NIS		Serbia	18000
19	Hacettepe University, School of Medicine; Pediatrics Department	Ankara		Turkey	06100
20	Istanbul University, Cerrahpasa Medical Faculty; Pediatrics Department	Istanbul		Turkey	34098
21	Alder Hey Children s Hospital; Department of Pediatrics	Liverpool		United Kingdom	L12 2AP
22	Great Ormond Street Children's Hospital; Centre of Paediatric & Adolescent Rheumatology	London		United Kingdom	WC1N 1EH
23	Nottingham Children's Hospital	Nottingham		United Kingdom	NG7 2UH

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Apr 26, 2016
• Statistical Analysis Plan - Sep 10, 2018

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01750697
• Other Study ID Numbers: WA25615; 2012-002062-13
• First Posted: Dec 17, 2012
• Last Update Posted: Jun 26, 2019
• Last Verified: Jun 1, 2019

• Additional relevant MeSH terms: Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Systemic Vasculitis; Rituximab

Study Results

Participant Flow

Recruitment Details	A total of 25 participants were enrolled in the study over a 3.5 year period from 11 sites across the United Kingdom, Italy, Serbia, Turkey, Canada and the United States.
Pre-assignment Detail	The screening visit occurred up to 28 days prior to the Day 1 baseline visit. Following successful screening, eligible participants entered the 6 month Remission Induction Phase of the study.

Arm/Group Title	Rituximab
Arm/Group Description	Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Period Title: Overall Study
STARTED	25
Completed	25
Follow-up Phase	24
COMPLETED	16
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Rituximab
Arm/Group Description	Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Overall Participants	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.4 (2.9)
Sex: Female, Male (Count of Participants)
Female	20 80%
Male	5 20%
Race/Ethnicity, Customized (participants) [Number]
Asian	4 16%
Black or African American	1 4%
White	17 68%
Multiple	1 4%
Other	2 8%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least part of one infusion of rituximab.

Arm/Group Title	Remission Induction Phase (up to 6 Mos.) Rituximab	Overall Follow-up Phase (up to 4.5 Yrs) Rituximab
Arm/Group Description	Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per metre squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during Remission Induction Phase (Day 1 (baseline) to Month 6)	Participants who received rituximab during the Remission Induction Phase were followed for a minimum of 18 months during the Follow-up Phase and could receive additional rituximab or other treatments for GPA/MPA (Day 1 (baseline) up to 4.5 yrs)
Measure Participants	25	25
Percentage of Participants with AEs	100 400%	100 NaN
Percentage of Participants with SAEs	28 112%	48 NaN

2. Primary Outcome

Title	Pharmacokinetics: Rituximab Clearance (CL)
Description	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

Outcome Measure Data

Analysis Population Description

The PK analysis population included all participants in the safety population who provided at least one evaluable PK sample.

Arm/Group Title	Rituximab (Experimental)
Arm/Group Description	Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Measure Participants	25
Geometric Mean (Geometric Coefficient of Variation) [mL/day]	204 (0.414)

3. Primary Outcome

Title	Pharmacokinetics: Volume of Distribution (Vd) of Rituximab
Description	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

Outcome Measure Data

Analysis Population Description

The PK analysis population included all participants in the safety population who provided at least one evaluable PK sample.

Arm/Group Title	Rituximab (Experimental)
Arm/Group Description	Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Measure Participants	25
Geometric Mean (Geometric Coefficient of Variation) [mL]	2220 (0.212)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The PK analysis population included all participants in the safety population who provided at least one evaluable PK sample.

Arm/Group Title	Rituximab (Experimental)
Arm/Group Description	Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Measure Participants	25
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL*day]	10120 (0.42)

5. Secondary Outcome

Title	Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Rituximab
Description	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

Outcome Measure Data

Analysis Population Description

The PK analysis population included all participants in the safety population who provided at least one evaluable PK sample.

Arm/Group Title	Rituximab (Experimental)
Arm/Group Description	Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Measure Participants	25
1st Dose	230 (0.166)
2nd Dose	305 (0.181)
3rd Dose	353 (0.183)
4th Dose	378 (0.174)

Adverse Events

Time Frame	Up to approximately 5 years
Adverse Event Reporting Description	The safety population included all participants who received at least part of one infusion of rituximab.
Arm/Group Title	Remission Induction Phase: Rituximab		Overall Follow-up Phase: Rituximab
Arm/Group Description	Participants received rituximab as an IV infusion of 375 mg/m^2 once a week on Days 1, 8, 15 and 22 during Remission Induction Phase (Day 1 (baseline) to Month 6)		Participants who received rituximab during the remission induction phase were followed for a minimum of 18 months during the follow-up phase and could receive additional rituximab or other treatments for GPA/MPA (Day 1 (baseline) up to 4.5 yrs)
All Cause Mortality
	Remission Induction Phase: Rituximab		Overall Follow-up Phase: Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)
Serious Adverse Events
	Remission Induction Phase: Rituximab		Overall Follow-up Phase: Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/25 (28%)		12/25 (48%)
Blood and lymphatic system disorders
Sickle cell anaemia with crisis	0/25 (0%)		1/25 (4%)
Congenital, familial and genetic disorders
Sickle cell anaemia	0/25 (0%)		1/25 (4%)
Gastrointestinal disorders
Pancreatitis	0/25 (0%)		1/25 (4%)
Immune system disorders
Anti-neutrophil cytoplasmic antibody positive vasculitis	0/25 (0%)		1/25 (4%)
Infections and infestations
Device related sepsis	0/25 (0%)		1/25 (4%)
Eye infection bacterial	0/25 (0%)		1/25 (4%)
Gastroenteritis norovirus	0/25 (0%)		1/25 (4%)
Gastroenteritis viral	1/25 (4%)		1/25 (4%)
Influenza	1/25 (4%)		2/25 (8%)
Lower respiratory tract infection	1/25 (4%)		2/25 (8%)
Sinusitis	0/25 (0%)		1/25 (4%)
Injury, poisoning and procedural complications
Infusion related reaction	1/25 (4%)		1/25 (4%)
Musculoskeletal and connective tissue disorders
Myopathy	1/25 (4%)		1/25 (4%)
Nervous system disorders
Seizure	0/25 (0%)		1/25 (4%)
Psychiatric disorders
Suicidal ideation	0/25 (0%)		1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Bronchostenosis	1/25 (4%)		1/25 (4%)
Laryngeal obstruction	0/25 (0%)		1/25 (4%)
Vascular disorders
Granulomatosis with polyangiitis	2/25 (8%)		4/25 (16%)
Vasculitis	1/25 (4%)		1/25 (4%)
Other (Not Including Serious) Adverse Events
	Remission Induction Phase: Rituximab		Overall Follow-up Phase: Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/25 (88%)		24/25 (96%)
Blood and lymphatic system disorders
Neutropenia	0/25 (0%)		2/25 (8%)
Ear and labyrinth disorders
Deafness unilateral	0/25 (0%)		2/25 (8%)
Gastrointestinal disorders
Abdominal pain	2/25 (8%)		3/25 (12%)
Abdominal pain upper	3/25 (12%)		4/25 (16%)
Constipation	3/25 (12%)		3/25 (12%)
Diarrhoea	0/25 (0%)		7/25 (28%)
Gastritis	0/25 (0%)		2/25 (8%)
Nausea	4/25 (16%)		5/25 (20%)
Vomiting	2/25 (8%)		4/25 (16%)
General disorders
Chest pain	2/25 (8%)		3/25 (12%)
Non-cardiac chest pain	0/25 (0%)		2/25 (8%)
Immune system disorders
Hypogammaglobulinaemia	0/25 (0%)		3/25 (12%)
Infections and infestations
Conjunctivitis	2/25 (8%)		5/25 (20%)
Ear infection	0/25 (0%)		3/25 (12%)
Fungal skin infection	0/25 (0%)		2/25 (8%)
Gastroenteritis	2/25 (8%)		3/25 (12%)
Herpes zoster	0/25 (0%)		2/25 (8%)
Influenza	0/25 (0%)		4/25 (16%)
Lower respiratory tract infection	0/25 (0%)		3/25 (12%)
Nasopharyngitis	2/25 (8%)		5/25 (20%)
Oral herpes	2/25 (8%)		2/25 (8%)
Pharyngitis	0/25 (0%)		3/25 (12%)
Pneumonia	0/25 (0%)		2/25 (8%)
Sinusitis	0/25 (0%)		3/25 (12%)
Tooth infection	0/25 (0%)		2/25 (8%)
Upper respiratory tract infection	4/25 (16%)		12/25 (48%)
Urinary tract infection	0/25 (0%)		3/25 (12%)
Viral upper respiratory tract infection	2/25 (8%)		4/25 (16%)
Injury, poisoning and procedural complications
Fall	0/25 (0%)		2/25 (8%)
Infusion related reaction	14/25 (56%)		16/25 (64%)
Skin abrasion	0/25 (0%)		2/25 (8%)
Investigations
Blood immunoglobulin G decreased	2/25 (8%)		2/25 (8%)
C-reactive protein increased	0/25 (0%)		2/25 (8%)
Serum ferritin decreased	0/25 (0%)		2/25 (8%)
Metabolism and nutrition disorders
Iron deficiency	0/25 (0%)		2/25 (8%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/25 (12%)		5/25 (20%)
Back pain	3/25 (12%)		5/25 (20%)
Musculoskeletal chest pain	0/25 (0%)		2/25 (8%)
Pain in extremity	2/25 (8%)		4/25 (16%)
Nervous system disorders
Headache	4/25 (16%)		9/25 (36%)
Migraine	0/25 (0%)		3/25 (12%)
Tremor	2/25 (8%)		2/25 (8%)
Psychiatric disorders
Depression	0/25 (0%)		2/25 (8%)
Insomnia	0/25 (0%)		2/25 (8%)
Reproductive system and breast disorders
Amenorrhoea	2/25 (8%)		2/25 (8%)
Respiratory, thoracic and mediastinal disorders
Cough	3/25 (12%)		6/25 (24%)
Dyspnoea	0/25 (0%)		2/25 (8%)
Epistaxis	3/25 (12%)		7/25 (28%)
Oropharyngeal pain	0/25 (0%)		2/25 (8%)
Skin and subcutaneous tissue disorders
Erythema	0/25 (0%)		3/25 (12%)
Pruritus	2/25 (8%)		2/25 (8%)
Purpura	0/25 (0%)		2/25 (8%)
Rash	0/25 (0%)		2/25 (8%)
Rash erythematous	2/25 (8%)		2/25 (8%)
Skin striae	2/25 (8%)		2/25 (8%)
Vascular disorders
Granulomatosis with polyangiitis	0/25 (0%)		2/25 (8%)
Hypertension	2/25 (8%)		3/25 (12%)

Limitations/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%).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.