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An Observational Study of The Safety of MabThera/Rituxan (Rituximab) in Participants With Granulomatosis With Polyangiitis (Wegener's) or Microscopic Polyangiitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01613599
Recruitment Status : Completed
First Posted : June 7, 2012
Results First Posted : August 17, 2016
Last Update Posted : July 26, 2018
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Conditions Granulomatosis With Polyangiitis
Microscopic Polyangiitis
Intervention Drug: Rituximab
Enrollment 100
Recruitment Details A total of 100 participants were enrolled in 15 investigational sites in United States. 3 participants out of 100 enrolled participants were not included in the analysis population as that site became unresponsive.
Pre-assignment Details  
Arm/Group Title Rituximab
Hide Arm/Group Description Participants with granulomatosis with polyangiitis (GPA) (Wegener’s granulomatosis) or microscopic polyangiitis (MPA) who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Period Title: Overall Study
Started 97
Completed 72
Not Completed 25
Reason Not Completed
Death             9
Lost to Follow-up             5
Withdrawal by Subject             8
Reason not specified             3
Arm/Group Title Rituximab
Hide Arm/Group Description Participants with GPA (Wegener’s granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Overall Number of Baseline Participants 97
Hide Baseline Analysis Population Description
The safety population included all participants who received any active dose of rituximab.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 97 participants
56.3  (16.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 97 participants
Female
57
  58.8%
Male
40
  41.2%
1.Primary Outcome
Title Incidence Rate of Serious Infections
Hide Description A serious infection was defined as an infection that was a serious adverse event (SAE) or a non-SAE infection that required treatment with intravenous antimicrobials. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time Frame From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received any active dose of rituximab.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Participants with GPA (Wegener’s granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Overall Number of Participants Analyzed 97
Overall Number of Units Analyzed
Type of Units Analyzed: Total Patient-years at Risk
338
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100 patient year
7.11
(4.55 to 10.58)
2.Secondary Outcome
Title Percentage of Participants With a Serious Infusion-related Reaction
Hide Description A serious infusion-related reaction was defined as a SAE during or within 24 hours after any rituximab infusion and considered infusion related by the Principal Investigator. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above.
Time Frame From the start of an infusion up to 24 hours following infusion completion (Up to 4.32 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received any active dose of rituximab.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Participants with GPA (Wegener’s granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Overall Number of Participants Analyzed 97
Measure Type: Number
Unit of Measure: percentage of participants
0
3.Secondary Outcome
Title Incidence Rate of Serious Cardiac Adverse Events
Hide Description A serious cardiac adverse event was defined as a SAE that was coded to the Medical Dictionary for Regulatory Activities (MedDRA) cardiac system organ class. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time Frame From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received any active dose of rituximab.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Participants with GPA (Wegener’s granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Overall Number of Participants Analyzed 97
Overall Number of Units Analyzed
Type of Units Analyzed: Total Patient-years at Risk
338
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100 patient year
5.03
(2.93 to 8.06)
4.Secondary Outcome
Title Percentage of Participants With Any Serious Adverse Events During or Within 24 Hours After Any Rituximab Infusion
Hide Description A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above.
Time Frame From the start of an infusion up to 24 hours following infusion completion (Up to 4.32 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received any active dose of rituximab.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Participants with GPA (Wegener’s granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Overall Number of Participants Analyzed 97
Measure Type: Number
Unit of Measure: percentage of participants
0
5.Secondary Outcome
Title Incidence Rate of Serious Vascular Adverse Events
Hide Description A serious vascular adverse event was defined as a SAE coded to the MedDRA vascular system organ class. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time Frame From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received any active dose of rituximab.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Participants with GPA (Wegener’s granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Overall Number of Participants Analyzed 97
Overall Number of Units Analyzed
Type of Units Analyzed: Total Patient-years at Risk
338
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100 patient year
2.37
(1.02 to 4.67)
6.Secondary Outcome
Title Incidence Rate of Malignancy, Excluding Non-melanoma Skin Cancer
Hide Description Malignancies were clinical findings of cancer and excluded non-melanoma skin cancer. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time Frame From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received any active dose of rituximab.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Participants with GPA (Wegener’s granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Overall Number of Participants Analyzed 97
Overall Number of Units Analyzed
Type of Units Analyzed: Total Patient-years at Risk
338
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100 patient year
0.89
(0.18 to 2.60)
7.Secondary Outcome
Title Incidence Rate of Serious Adverse Events
Hide Description A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time Frame From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received any active dose of rituximab.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Participants with GPA (Wegener’s granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Overall Number of Participants Analyzed 97
Overall Number of Units Analyzed
Type of Units Analyzed: Total Patient-years at Risk
338
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100 patient year
27.84
(22.50 to 34.07)
8.Secondary Outcome
Title Incidence Rate of Adverse Events With Fatal Outcomes
Hide Description Incidence rate is defined as events per 100 patient years.
Time Frame From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received any active dose of rituximab.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Participants with GPA (Wegener’s granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Overall Number of Participants Analyzed 97
Overall Number of Units Analyzed
Type of Units Analyzed: Total Patient-years at Risk
338
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100 patient year
2.67
(1.22 to 5.06)
9.Secondary Outcome
Title Incidence Rate of Serious Adverse Events in Participants Who Received Re-treatment With MabThera/Rituximab
Hide Description A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time Frame From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The re-treated safety population was a subset of the safety population and included all participants who received more than one course of rituximab.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Participants with GPA (Wegener’s granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Overall Number of Participants Analyzed 71
Overall Number of Units Analyzed
Type of Units Analyzed: Total Patient-years at Risk
264
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100 patient year
23.90
(18.36 to 30.58)
10.Secondary Outcome
Title Incidence Rate of Serious Infections in Participants Who Received Re-treatment With MabThera/Rituximab
Hide Description A serious infection was defined as an infection that was a serious adverse event (SAE) or a non-SAE infection that required treatment with intravenous antimicrobials. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time Frame From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The re-treated safety population was a subset of the safety population and included all participants who received more than one course of rituximab.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Participants with GPA (Wegener’s granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years.
Overall Number of Participants Analyzed 71
Overall Number of Units Analyzed
Type of Units Analyzed: Total Patient-years at Risk
264
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100 patient year
6.07
(3.47 to 9.86)
Time Frame Enrollment of the first participant to time of withdrawal or last participant visit (Up to 4.32 years)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rituximab
Hide Arm/Group Description Participants with GPA (Wegener's granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years
All-Cause Mortality
Rituximab
Affected / at Risk (%)
Total   9/97 (9.28%) 
Hide Serious Adverse Events
Rituximab
Affected / at Risk (%)
Total   38/97 (39.18%) 
Blood and lymphatic system disorders   
Thrombocytopenia  2  1/97 (1.03%) 
Cardiac disorders   
Atrial fibrillation  2  5/97 (5.15%) 
Atrial flutter  2  2/97 (2.06%) 
Angina pectoris  2  1/97 (1.03%) 
Cardiac failure congestive  2  1/97 (1.03%) 
Cardio-respiratory arrest  2  1/97 (1.03%) 
Myocardial infarction  2  1/97 (1.03%) 
Supraventricular tachycardia  2  1/97 (1.03%) 
Atrial tachycardia  2  1/97 (1.03%) 
Bradycardia  2  1/97 (1.03%) 
Ear and labyrinth disorders   
Vertigo  2  1/97 (1.03%) 
Vertigo positional  2  1/97 (1.03%) 
Gastrointestinal disorders   
Abdominal pain  2  1/97 (1.03%) 
Gastrointestinal haemorrhage  2  1/97 (1.03%) 
Oesophagitis  2  1/97 (1.03%) 
Lower gastrointestinal haemorrhage  2  1/97 (1.03%) 
General disorders   
Death  1  4/97 (4.12%) 
Chest pain  2  2/97 (2.06%) 
Asthenia  2  1/97 (1.03%) 
Infections and infestations   
Gastroenteritis  1  2/97 (2.06%) 
Influenza  2  2/97 (2.06%) 
Pneumonia  2  2/97 (2.06%) 
Staphylococcal bacteraemia  2  2/97 (2.06%) 
Bacteraemia  2  1/97 (1.03%) 
Bronchitis  2  1/97 (1.03%) 
Cellulitis  2  1/97 (1.03%) 
Endocarditis  2  1/97 (1.03%) 
Herpes zoster  2  2/97 (2.06%) 
Pneumonia bacterial  2  1/97 (1.03%) 
Pneumonia legionella  2  1/97 (1.03%) 
Sepsis  2  1/97 (1.03%) 
Septic shock  2  1/97 (1.03%) 
Urinary tract infection  2  2/97 (2.06%) 
Upper respiratory tract infection  2  1/97 (1.03%) 
Injury, poisoning and procedural complications   
Pubis fracture  2  1/97 (1.03%) 
Fall  2  1/97 (1.03%) 
Hip fracture  2  1/97 (1.03%) 
Investigations   
Blood creatinine increased  2  1/97 (1.03%) 
Metabolism and nutrition disorders   
Fluid overload  2  1/97 (1.03%) 
Hypercalcaemia  2  1/97 (1.03%) 
Musculoskeletal and connective tissue disorders   
Back pain  2  1/97 (1.03%) 
Osteoporosis  2  1/97 (1.03%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Adenocarcinoma  2  1/97 (1.03%) 
Lung adenocarcinoma  2  1/97 (1.03%) 
Nervous system disorders   
Ischaemic stroke  2  1/97 (1.03%) 
Metabolic encephalopathy  2  1/97 (1.03%) 
Renal and urinary disorders   
Cystitis haemorrhagic  2  1/97 (1.03%) 
Respiratory, thoracic and mediastinal disorders   
Haemoptysis  2  2/97 (2.06%) 
Hypoxia  2  2/97 (2.06%) 
Laryngeal stenosis  2  2/97 (2.06%) 
Chronic obstructive pulmonary disease  2  1/97 (1.03%) 
Dyspnoea  2  1/97 (1.03%) 
Interstitial lung disease  2  1/97 (1.03%) 
Pneumothroax  2  1/97 (1.03%) 
Pneumothorax spontaneous  2  1/97 (1.03%) 
Pulmonary alveolar haemorrhage  2  1/97 (1.03%) 
Pulmonary embolism  2  1/97 (1.03%) 
Pulmonary oedema  2  1/97 (1.03%) 
Pulmonary haemorrhage  2  1/97 (1.03%) 
Lung infiltration  2  1/97 (1.03%) 
Surgical and medical procedures   
Renal transplant  2  1/97 (1.03%) 
Vascular disorders   
Deep vein thrombosis  2  5/97 (5.15%) 
Orthostatic hypotension  2  1/97 (1.03%) 
Haematoma  2  1/97 (1.03%) 
1
Term from vocabulary, MedDRA 18.0
2
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rituximab
Affected / at Risk (%)
Total   5/97 (5.15%) 
Respiratory, thoracic and mediastinal disorders   
Throat irritation  1  5/97 (5.15%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffman-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01613599    
Other Study ID Numbers: WA27893
First Submitted: June 4, 2012
First Posted: June 7, 2012
Results First Submitted: July 6, 2016
Results First Posted: August 17, 2016
Last Update Posted: July 26, 2018