Trial Outcomes & Findings for MEmbranous Nephropathy Trial Of Rituximab (NCT NCT01180036)
NCT ID: NCT01180036
Last Updated: 2019-04-30
Results Overview
The number of subjects to reach the composite of maintaining complete remission or partial remission at 24 months after randomization will be the primary endpoint.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
130 participants
Primary outcome timeframe
24 months after randomization
Results posted on
2019-04-30
Participant Flow
Participant milestones
| Measure |
Rituximab Treatment Arm
Patients randomized to the RTX arm will receive 1000 mg IV on Days 1 and 15. Patients who achieve complete remission at 6 months will not be retreated. A second course of RTX 1000 mg IV will be administered at study month 6 for individuals who have not achieved a complete remission, but have achieved a minimum of \>25% reduction in Time 0 proteinuria. Dosing at study month 6 will be independent of CD19+ B cell count.
Rituximab: 1000 mg, I.V. on Days 1 and 15 and will be retreated at month 6 independent of CD19+ B cell count
|
Cyclosporine Treatment Arm
Patients randomized to the Cyclosporine arm will be started at a dose of CsA = 3.5 mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Target trough CsA blood levels are 125 to 175 ng/ml. Patients will have their doses adjusted according to their blood levels of CSA as monitored every 2 weeks until the target trough level is reached. If a complete remission is achieved by 6 months, CSA will be tapered and discontinued over a three-month period. If after 6 months there has not been a reduction in proteinuria of at least 25% of baseline values, the drug will also be discontinued. If there has been a \>25% reduction in baseline proteinuria (but not complete remission) the CSA will be continued for an additional 6 months.
|
|---|---|---|
|
Overall Study
STARTED
|
65
|
65
|
|
Overall Study
COMPLETED
|
65
|
65
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
MEmbranous Nephropathy Trial Of Rituximab
Baseline characteristics by cohort
| Measure |
Rituximab Treatment Arm
n=65 Participants
Patients randomized to the RTX arm will receive 1000 mg IV on Days 1 and 15. Patients who achieve complete remission at 6 months will not be retreated. A second course of RTX 1000 mg IV will be administered at study month 6 for individuals who have not achieved a complete remission, but have achieved a minimum of \>25% reduction in Time 0 proteinuria. Dosing at study month 6 will be independent of CD19+ B cell count.
Rituximab: 1000 mg, I.V. on Days 1 and 15 and will be retreated at month 6 independent of CD19+ B cell count
|
Cyclosporine Treatment Arm
n=65 Participants
Patients randomized to the Cyclosporine arm will be started at a dose of CsA = 3.5 mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Target trough CsA blood levels are 125 to 175 ng/ml. Patients will have their doses adjusted according to their blood levels of CSA as monitored every 2 weeks until the target trough level is reached. If a complete remission is achieved by 6 months, CSA will be tapered and discontinued over a three-month period. If after 6 months there has not been a reduction in proteinuria of at least 25% of baseline values, the drug will also be discontinued. If there has been a \>25% reduction in baseline proteinuria (but not complete remission) the CSA will be continued for an additional 6 months.
|
Total
n=130 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.9 years
STANDARD_DEVIATION 12.6 • n=5 Participants
|
52.2 years
STANDARD_DEVIATION 12.4 • n=7 Participants
|
52.0 years
STANDARD_DEVIATION 12.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
51 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
20 participants
n=5 Participants
|
20 participants
n=7 Participants
|
40 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
45 participants
n=5 Participants
|
45 participants
n=7 Participants
|
90 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 months after randomizationThe number of subjects to reach the composite of maintaining complete remission or partial remission at 24 months after randomization will be the primary endpoint.
Outcome measures
| Measure |
Rituximab Treatment Arm
n=65 Participants
Patients randomized to the Rituximab (RTX) arm will receive 1000 mg IV on Days 1 and 15. Patients who achieve complete remission at 6 months will not be retreated. A second course of RTX 1000 mg IV will be administered at study month 6 for individuals who have not achieved a complete remission, but have achieved a minimum of \>25% reduction in Time 0 proteinuria. Dosing at study month 6 will be independent of Cluster of Differentiation 19 (CD19)+ B cell count.
Rituximab: 1000 mg, I.V. on Days 1 and 15 and will be retreated at month 6 independent of CD19+ B cell count
|
Cyclosporine Treatment Arm
n=65 Participants
Patients randomized to the Cyclosporine (CsA) arm will be started at a dose of CsA = 3.5 mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Target trough CsA blood levels are 125 to 175 ng/ml. Patients will have their doses adjusted according to their blood levels of CSA as monitored every 2 weeks until the target trough level is reached. If a complete remission is achieved by 6 months, CSA will be tapered and discontinued over a three-month period. If after 6 months there has not been a reduction in proteinuria of at least 25% of baseline values, the drug will also be discontinued. If there has been a \>25% reduction in baseline proteinuria (but not complete remission) the CSA will be continued for an additional 6 months.
|
|---|---|---|
|
Remission Status
|
39 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: 12 months after randomizationThe number of subjects to reach either complete remission or partial remission at 12 months after randomization.
Outcome measures
| Measure |
Rituximab Treatment Arm
n=65 Participants
Patients randomized to the Rituximab (RTX) arm will receive 1000 mg IV on Days 1 and 15. Patients who achieve complete remission at 6 months will not be retreated. A second course of RTX 1000 mg IV will be administered at study month 6 for individuals who have not achieved a complete remission, but have achieved a minimum of \>25% reduction in Time 0 proteinuria. Dosing at study month 6 will be independent of Cluster of Differentiation 19 (CD19)+ B cell count.
Rituximab: 1000 mg, I.V. on Days 1 and 15 and will be retreated at month 6 independent of CD19+ B cell count
|
Cyclosporine Treatment Arm
n=65 Participants
Patients randomized to the Cyclosporine (CsA) arm will be started at a dose of CsA = 3.5 mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Target trough CsA blood levels are 125 to 175 ng/ml. Patients will have their doses adjusted according to their blood levels of CSA as monitored every 2 weeks until the target trough level is reached. If a complete remission is achieved by 6 months, CSA will be tapered and discontinued over a three-month period. If after 6 months there has not been a reduction in proteinuria of at least 25% of baseline values, the drug will also be discontinued. If there has been a \>25% reduction in baseline proteinuria (but not complete remission) the CSA will be continued for an additional 6 months.
|
|---|---|---|
|
Remission Status
|
39 Participants
|
34 Participants
|
Adverse Events
Rituximab Treatment Arm
Serious events: 11 serious events
Other events: 46 other events
Deaths: 0 deaths
Cyclosporine Treatment Arm
Serious events: 20 serious events
Other events: 51 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rituximab Treatment Arm
n=65 participants at risk
Patients randomized to the RTX arm will receive 1000 mg IV on Days 1 and 15. Patients who achieve complete remission at 6 months will not be retreated. A second course of RTX 1000 mg IV will be administered at study month 6 for individuals who have not achieved a complete remission, but have achieved a minimum of \>25% reduction in Time 0 proteinuria. Dosing at study month 6 will be independent of CD19+ B cell count.
Rituximab: 1000 mg, I.V. on Days 1 and 15 and will be retreated at month 6 independent of CD19+ B cell count
|
Cyclosporine Treatment Arm
n=65 participants at risk
Patients randomized to the Cyclosporine arm will be started at a dose of CsA = 3.5 mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Target trough CsA blood levels are 125 to 175 ng/ml. Patients will have their doses adjusted according to their blood levels of CSA as monitored every 2 weeks until the target trough level is reached. If a complete remission is achieved by 6 months, CSA will be tapered and discontinued over a three-month period. If after 6 months there has not been a reduction in proteinuria of at least 25% of baseline values, the drug will also be discontinued. If there has been a \>25% reduction in baseline proteinuria (but not complete remission) the CSA will be continued for an additional 6 months.
|
|---|---|---|
|
General disorders
Benign neoplasms
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
0.00%
0/65 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Blood and lymphatic system disorders
Blood and lymphatic system
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Cardiac disorders
Cardiovascular
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
10.8%
7/65 • Number of events 7 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Endocrine disorders
Endocrine or metabolic
|
3.1%
2/65 • Number of events 2 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
General disorders
General
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
0.00%
0/65 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Infections and infestations
Infections
|
6.2%
4/65 • Number of events 5 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
12.3%
8/65 • Number of events 8 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
0.00%
0/65 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
1.5%
1/65 • Number of events 2 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Nervous system disorders
Nervous system
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Renal and urinary disorders
Renal and urinary
|
0.00%
0/65 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
3.1%
2/65 • Number of events 2 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
0.00%
0/65 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
Other adverse events
| Measure |
Rituximab Treatment Arm
n=65 participants at risk
Patients randomized to the RTX arm will receive 1000 mg IV on Days 1 and 15. Patients who achieve complete remission at 6 months will not be retreated. A second course of RTX 1000 mg IV will be administered at study month 6 for individuals who have not achieved a complete remission, but have achieved a minimum of \>25% reduction in Time 0 proteinuria. Dosing at study month 6 will be independent of CD19+ B cell count.
Rituximab: 1000 mg, I.V. on Days 1 and 15 and will be retreated at month 6 independent of CD19+ B cell count
|
Cyclosporine Treatment Arm
n=65 participants at risk
Patients randomized to the Cyclosporine arm will be started at a dose of CsA = 3.5 mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Target trough CsA blood levels are 125 to 175 ng/ml. Patients will have their doses adjusted according to their blood levels of CSA as monitored every 2 weeks until the target trough level is reached. If a complete remission is achieved by 6 months, CSA will be tapered and discontinued over a three-month period. If after 6 months there has not been a reduction in proteinuria of at least 25% of baseline values, the drug will also be discontinued. If there has been a \>25% reduction in baseline proteinuria (but not complete remission) the CSA will be continued for an additional 6 months.
|
|---|---|---|
|
General disorders
Benign neoplasms
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Blood and lymphatic system disorders
Blood and lymphatic system
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
4.6%
3/65 • Number of events 3 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Cardiac disorders
Cardiovascular
|
7.7%
5/65 • Number of events 6 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
16.9%
11/65 • Number of events 14 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Ear and labyrinth disorders
Ear
|
4.6%
3/65 • Number of events 3 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
1.5%
1/65 • Number of events 2 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Endocrine disorders
Endocrine or metabolic
|
10.8%
7/65 • Number of events 9 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
9.2%
6/65 • Number of events 15 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Eye disorders
Eye
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Gastrointestinal disorders
Gastrointestinal
|
10.8%
7/65 • Number of events 11 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
27.7%
18/65 • Number of events 34 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
General disorders
General
|
38.5%
25/65 • Number of events 42 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
23.1%
15/65 • Number of events 24 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Immune system disorders
Immune system
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Infections and infestations
Infections
|
26.2%
17/65 • Number of events 28 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
30.8%
20/65 • Number of events 26 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Injury, poisoning and procedural complications
Injury
|
4.6%
3/65 • Number of events 3 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
15.4%
10/65 • Number of events 17 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
27.7%
18/65 • Number of events 27 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Nervous system disorders
Nervous system
|
16.9%
11/65 • Number of events 15 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
24.6%
16/65 • Number of events 26 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
0.00%
0/65 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Psychiatric disorders
Psychiatric
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
7.7%
5/65 • Number of events 7 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Renal and urinary disorders
Renal and Urinary
|
9.2%
6/65 • Number of events 8 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
24.6%
16/65 • Number of events 19 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Reproductive system and breast disorders
Reproductive system and breast
|
4.6%
3/65 • Number of events 4 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
1.5%
1/65 • Number of events 1 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory
|
13.8%
9/65 • Number of events 13 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
9.2%
6/65 • Number of events 11 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
|
Skin and subcutaneous tissue disorders
Skin
|
18.5%
12/65 • Number of events 14 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
7.7%
5/65 • Number of events 5 • Adverse events will be collected from enrollment through month 18, for each subject, approximately 18 months total.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place