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Rituximab and Belimumab for Lupus Nephritis (CALIBRATE)

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: NCT02260934
Recruitment Status : Completed
First Posted : October 9, 2014
Results First Posted : April 8, 2019
Last Update Posted : March 24, 2020
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lupus Nephritis
Interventions Biological: Rituximab
Drug: Cyclophosphamide
Drug: Prednisone
Drug: Methylprednisolone
Drug: Diphenhydramine
Drug: Acetaminophen
Biological: Belimumab
Enrollment 43
Recruitment Details Of the 59 participants screened, 43 were enrolled at 14 sites in the US from July 9, 2015 to May 22, 2017.
Pre-assignment Details Prior to randomization, enrolled participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone was administered at 40 mg/day for the first 2 weeks, followed by a guided steroid taper. Participants were randomized at Week 4.
Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone was administered at 40 mg/day for the first 2 weeks, followed by a guided steroid taper to 10 mg/day by Week 12. Prednisone was continued through to Week 96 at 10 mg/day, with the potential of a taper to a minimum of 5 mg/day. Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone was administered at 40 mg/day for the first 2 weeks, followed by a guided steroid taper to 10 mg/day by Week 12. Prednisone was continued through to Week 96 at 10 mg/day, with the potential of a taper to a minimum of 5 mg/day. In addition, participants received IV belimumab 10mg/kg at Weeks 4, 6, 8, and then every 4 weeks through Week 48 in addition to prednisone.
Period Title: Overall Study
Started 22 21
Completed 19 [1] 17 [2]
Not Completed 3 4
Reason Not Completed
Lost to Follow-up             2             1
Withdrawal by Subject             0             2
Participant Relocated             1             0
Site error             0             1
[1]
At primary outcome timepoint: Ten participants engaged in ongoing scheduled study visits.
[2]
At primary outcome timepoint: Eleven participants engaged in ongoing scheduled study visits.
Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB) Total
Hide Arm/Group Description Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone was administered at 40 mg/day for the first 2 weeks, followed by a guided steroid taper to 10 mg/day by Week 12. Prednisone was continued through to Week 96 at 10 mg/day, with the potential of a taper to a minimum of 5 mg/day. Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone was administered at 40 mg/day for the first 2 weeks, followed by a guided steroid taper to 10 mg/day by Week 12. Prednisone was continued through to Week 96 at 10 mg/day, with the potential of a taper to a minimum of 5 mg/day. In addition, participants received IV belimumab 10mg/kg at Weeks 4, 6, 8, and then every 4 weeks through Week 48 in addition to prednisone. Total of all reporting groups
Overall Number of Baseline Participants 22 21 43
Hide Baseline Analysis Population Description
Participants who signed informed consent and were enrolled in the study. Reported baseline measurements are the most recent measurements for a participant taken between the Screening Visit (occurring within 21 days of Week 0/Study Enrollment) and Week 0 (Study Enrollment).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 21 participants 43 participants
32.3  (11.4) 34.5  (9.1) 33.4  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
Female
18
  81.8%
19
  90.5%
37
  86.0%
Male
4
  18.2%
2
   9.5%
6
  14.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
Hispanic or Latino
10
  45.5%
5
  23.8%
15
  34.9%
Not Hispanic or Latino
12
  54.5%
16
  76.2%
28
  65.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
  13.6%
2
   9.5%
5
  11.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
9
  40.9%
8
  38.1%
17
  39.5%
White
7
  31.8%
9
  42.9%
16
  37.2%
More than one race
1
   4.5%
1
   4.8%
2
   4.7%
Unknown or Not Reported
2
   9.1%
1
   4.8%
3
   7.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 22 participants 21 participants 43 participants
22
 100.0%
21
 100.0%
43
 100.0%
Urine Protein-to-Creatinine Ratio (UPCR) from 24 Hour Collection   [1] 
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 22 participants 21 participants 43 participants
3.4  (1.5) 3.3  (2.5) 3.4  (2.0)
[1]
Measure Description: Urine protein-to-creatinine ratio (UPCR) from a 24-hour collection is a measure of lupus nephritis disease activity. Higher ratios indicate poorer kidney function. Elevated ratio: >3.
Elevated Urine Protein-to-Creatinine Ratio (UPCR)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
14
  63.6%
8
  38.1%
22
  51.2%
[1]
Measure Description: Count of participants with a urine protein-to-creatinine ratio (UPCR) from a 24-hour collection that was >3.
Serum Creatinine   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 22 participants 21 participants 43 participants
1.0  (0.4) 1.0  (0.5) 1.0  (0.4)
[1]
Measure Description: Serum creatinine is a measure of renal function. Normal values: 0.67 to 1.18mg/dL for men and 0.51 to 0.95mg/dL for women. Higher results indicate poorer kidney function.
Estimated glomerular filtration rate (eGFR)   [1] 
Mean (Standard Deviation)
Unit of measure:  mL/min/1.73m^2
Number Analyzed 22 participants 21 participants 43 participants
92.7  (36.0) 89.1  (33.9) 90.9  (34.6)
[1]
Measure Description: Estimated glomerular filtration rate (eGFR) is a measure of renal function. Methodology: Calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula based on serum creatinine, age, sex and race. Normal GFR: ≥90 mL/min/1.73m^2. Lower GFRs reflect poorer kidney function.
Serum Albumin   [1] 
Mean (Standard Deviation)
Unit of measure:  g/dL
Number Analyzed 22 participants 21 participants 43 participants
3.0  (0.5) 2.9  (0.6) 2.9  (0.6)
[1]
Measure Description: Normal values: 3.7 to 4.9 g/dL.
B Cell Count   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  cells/µL
Number Analyzed 18 participants 18 participants 36 participants
160.5  (157.4) 216.0  (207.3) 188.3  (183.6)
[1]
Measure Description: Total B cell number in the peripheral blood. B cell depletion was expected to occur in this study between Weeks 0 and 4, after initiation of rituximab and cyclophosphamide. Normal B Cell Count in the peripheral blood: 107 to 698 cells/µL.
[2]
Measure Analysis Population Description: Participants who signed informed consent and were enrolled in the study. Reported baseline measurements are the most recent measurements for a participant taken between the screening visit and Week 0.
Immunoglobulin G (IgG) Level   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 22 participants 21 participants 43 participants
1044.9  (408.9) 1057.1  (589.5) 1050.8  (499.1)
[1]
Measure Description: Immunoglobulin G (IgG) is a measure of immune function. Normal values: 700 to 1600 mg/dL.
Hypogammaglobulinemia   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
2
   9.1%
4
  19.0%
6
  14.0%
[1]
Measure Description: Count of participants with hypogammaglobulinemia at baseline, defined as having a serum Immunoglobulin G (IgG) level <450 mg/dL.
Anti-Double Stranded DNA (Anti-dsDNA) Positive   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
20
  90.9%
19
  90.5%
39
  90.7%
[1]
Measure Description: Count of participants who were anti-double stranded DNA (anti-dsDNA) positive at baseline, defined as anti-dsDNA levels >30 IU/mL. Anti-dsDNA levels are associated with systemic lupus erythematosus disease activity.
Hypocomplementemic for C3   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
18
  81.8%
16
  76.2%
34
  79.1%
[1]
Measure Description: Count of participants who were hypocomplementemic for C3, defined as a C3 level <90 mg/dL. Serum C3 complement is a protein which can be measured in the blood. Low blood levels of C3 are common in those with active lupus.
Hypocomplementemic for C4   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
10
  45.5%
8
  38.1%
18
  41.9%
[1]
Measure Description: Count of participants who were hypocomplementemic for C4, defined as C4 level <10 mg/dL. Serum C4 complement is a protein which can be measured in the blood. Low blood levels of C4 are common in those with active lupus.
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 22 participants 21 participants 43 participants
69.7  (18.0) 75.4  (26.0) 72.5  (22.2)
[1]
Measure Description: Body weight measurement taken before infusion of study drug.
Duration of Lupus Nephritis   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 21 participants 43 participants
4.8  (4.5) 6.8  (6.6) 5.8  (5.7)
[1]
Measure Description: Duration of lupus nephritis (LN) is the number of years at the screening visit since the onset of LN.
Duration of Lupus Nephritis More Than One Year   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 43 participants
> 1 year
18
  81.8%
18
  85.7%
36
  83.7%
≤ 1 year
4
  18.2%
3
  14.3%
7
  16.3%
[1]
Measure Description: Count of participants with a duration of lupus nephritis of greater than one year. Duration of lupus nephritis is defined by the number of years from onset of lupus nephritis to the screening visit.
1.Primary Outcome
Title Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96
Hide Description

The percentage of participants who experienced at least one Grade 3 or higher treatment-emergent infectious adverse event. The severity of adverse events (AEs) was classified into grades using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v4.03:June 14, 2010). Treatment-emergent AEs are those:

  • with an onset date on or after the first dose of study medication,
  • with onset before first dose but that worsened in severity after first dose, and
  • for which the start of the AE in relation to the start of study medication could not be established.

AEs were classified by system organ class and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA) version 17.0. Grade 3 or higher AEs were classified infectious based on the study team's review of the MedDRA body systems and preferred terms of the AEs.

Time Frame Week 0 to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description

The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.

Confidence intervals were calculated using Clopper-Pearson method.

Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone was administered at 40 mg/day for the first 2 weeks, followed by a guided steroid taper to 10 mg/day by Week 12. Prednisone was continued through to Week 96 at 10 mg/day, with the potential of a taper to a minimum of 5 mg/day.
Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone was administered at 40 mg/day for the first 2 weeks, followed by a guided steroid taper to 10 mg/day by Week 12. Prednisone was continued through to Week 96 at 10 mg/day, with the potential of a taper to a minimum of 5 mg/day. In addition, participants received IV belimumab 10mg/kg at Weeks 4, 6, 8, and then every 4 weeks through Week 48 in addition to prednisone.
Overall Number of Participants Analyzed 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 0 to Week 24
9.1
(1.1 to 29.2)
4.8
(0.1 to 23.8)
Week 0 to Week 48
22.7
(7.8 to 45.4)
9.5
(1.2 to 30.4)
Week 0 to Week 96
27.3
(10.7 to 50.2)
9.5
(1.2 to 30.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 0 to Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments Two-sided test
Method Regression, Logistic
Comments Treatment group was the independent variable in the logistic regression.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 0 to Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments Two-sided test.
Method Regression, Logistic
Comments Treatment group was the independent variable in the logistic regression.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 0 to Week 96.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments Two-sided test.
Method Regression, Logistic
Comments Treatment group was the independent variable in the logistic regression.
2.Secondary Outcome
Title Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96
Hide Description

The percentage of participants who achieved B cell reconstitution, defined as a peripheral blood total B cell count ≥ to the baseline count or the lower limit of normal, whichever was lower. Note: B cell depletion was expected to occur in this study between Weeks 0 and 4, after initiation of rituximab and cyclophosphamide.

Normal peripheral blood B Cell count: 107 to 698 cells/µL.

Time Frame Week 24, Week 48 and Week 96
Hide Outcome Measure Data
Hide Analysis Population Description

The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.

Confidence intervals were calculated using Clopper-Pearson method.

Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone was administered at 40 mg/day for the first 2 weeks, followed by a guided steroid taper to 10 mg/day by Week 12. Prednisone was continued through to Week 96 at 10 mg/day, with the potential of a taper to a minimum of 5 mg/day.
Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone was administered at 40 mg/day for the first 2 weeks, followed by a guided steroid taper to 10 mg/day by Week 12. Prednisone was continued through to Week 96 at 10 mg/day, with the potential of a taper to a minimum of 5 mg/day. In addition, participants received IV belimumab 10mg/kg at Weeks 4, 6, 8, and then every 4 weeks through Week 48 in addition to prednisone.
Overall Number of Participants Analyzed 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Week 24 Number Analyzed 16 participants 16 participants
31.3
(11.0 to 58.7)
6.3
(0.2 to 30.2)
Week 48 Number Analyzed 14 participants 17 participants
35.7
(12.8 to 64.9)
11.8
(1.5 to 36.4)
Week 96 Number Analyzed 15 participants 13 participants
40.0
(16.3 to 67.7)
30.8
(9.1 to 61.4)
3.Secondary Outcome
Title Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96
Hide Description The percentage of participants who experienced Grade 4 hypogammaglobulinemia, defined as having a serum Immunoglobulin G (IgG) level < 300 mg/dL. Severity of adverse events (AEs) was classified using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v4.03:June 14, 2010).
Time Frame Week 24, Week 48 and Week 96
Hide Outcome Measure Data
Hide Analysis Population Description

The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.

Confidence intervals were calculated using Clopper-Pearson method.

Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone was administered at 40 mg/day for the first 2 weeks, followed by a guided steroid taper to 10 mg/day by Week 12. Prednisone was continued through to Week 96 at 10 mg/day, with the potential of a taper to a minimum of 5 mg/day.
Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone was administered at 40 mg/day for the first 2 weeks, followed by a guided steroid taper to 10 mg/day by Week 12. Prednisone was continued through to Week 96 at 10 mg/day, with the potential of a taper to a minimum of 5 mg/day.
Overall Number of Participants Analyzed 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 0 to Week 24
0
(0.0 to 15.4)
0
(0.0 to 16.1)
Week 0 to Week 48
0
(0.0 to 15.4)
0
(0.0 to 16.1)
Week 0 to Week 96
0
(0.0 to 15.4)
0
(0.0 to 16.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 0 to Week 24
Type of Statistical Test Superiority
Comments P-value could not be produced because of zero count in at least one of the treatment arms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Two sided test. P-value could not be produced because of zero count in at least one of the treatment arms.
Other Statistical Analysis Treatment group was the independent variable in the logistic regression.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 0 to Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments P-value could not be produced because of zero count in at least one of the treatment arms.
Other Statistical Analysis P-value could not be produced because of zero count in at least one of the treatment arms.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 0 to Week 96 The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Type of Statistical Test Superiority
Comments P-value could not be produced because of zero count in at least one of the treatment arms
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments P-value could not be produced because of zero count in at least one of the treatment arms
Other Statistical Analysis P-value could not be produced because of zero count in at least one of the treatment arms
4.Secondary Outcome
Title Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96
Hide Description

The percentage of participants who achieved a complete response, defined as meeting all of the following criteria:

  1. Urine protein-to-creatinine ratio (UPCR) < 0.5, based on a 24-hour collection;
  2. Estimated glomerular filtration rate (eGFR) ≥ 120 ml/min/1.73 m^2 calculated by the CKD-EPI formula or, if < 120 ml/min/1.73 m^2, then > 80% of eGFR at entry; and
  3. Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.
Time Frame Week 24, Week 48 and Week 96
Hide Outcome Measure Data
Hide Analysis Population Description

The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.

Confidence intervals were calculated using Clopper-Pearson method.

Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Overall Number of Participants Analyzed 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 24 Number Analyzed 21 participants 20 participants
23.8
(8.2 to 47.2)
30.0
(11.9 to 54.3)
Week 48 Number Analyzed 20 participants 19 participants
35.0
(15.4 to 59.2)
42.1
(20.3 to 66.5)
Week 96 Number Analyzed 15 participants 14 participants
33.3
(11.8 to 61.6)
42.9
(17.7 to 71.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 24
Type of Statistical Test Superiority
Comments Treatment group was the independent variable in the logistic regression.
Statistical Test of Hypothesis P-Value 0.66
Comments Treatment group was the independent variable in the logistic regression.
Method Regression, Logistic
Comments 2 sided test
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 48
Type of Statistical Test Superiority
Comments Treatment group was the independent variable in the logistic regression.
Statistical Test of Hypothesis P-Value 0.65
Comments Treatment group was the independent variable in the logistic regression.
Method Regression, Logistic
Comments 2 sided test
Other Statistical Analysis Treatment group was the independent variable in the logistic regression.
5.Secondary Outcome
Title Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96
Hide Description

The percentage of participants who achieved an overall response, defined as meeting all of the following criteria:

  1. >50% improvement in the urine protein-to-creatinine ratio (UPCR) from study entry, based on a 24-hour collection;
  2. Estimated glomerular filtration rate (eGFR) ≥120 ml/min/1.73 m^2 calculated by the CKD-EPI formula or, if < 120 ml/min/1.73 m^2, then > 80% of eGFR at entry; and
  3. Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.
Time Frame Week 24, Week 48 and Week 96
Hide Outcome Measure Data
Hide Analysis Population Description

The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.

Confidence intervals were calculated using Clopper-Pearson method.

Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Overall Number of Participants Analyzed 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 24 Number Analyzed 21 participants 20 participants
46.7
(25.7 to 70.2)
55.0
(31.5 to 76.9)
Week 48 Number Analyzed 20 participants 19 participants
60.0
(36.1 to 80.9)
73.7
(48.8 to 90.9)
Week 96 Number Analyzed 15 participants 14 participants
53.3
(26.6 to 78.7)
71.4
(41.9 to 91.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 24 Treatment group was the independent variable in the logistic regression.
Type of Statistical Test Superiority
Comments Treatment group was the independent variable in the logistic regression.
Statistical Test of Hypothesis P-Value 0.64
Comments 2 sided test
Method Regression, Logistic
Comments Treatment group was the independent variable in the logistic regression.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 48
Type of Statistical Test Superiority
Comments Treatment group was the independent variable in the logistic regression.
Statistical Test of Hypothesis P-Value 0.37
Comments 2 sided test
Method Regression, Logistic
Comments Treatment group was the independent variable in the logistic regression.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 96
Type of Statistical Test Superiority
Comments Treatment group was the independent variable in the logistic regression.
Statistical Test of Hypothesis P-Value 0.32
Comments [Not Specified]
Method Regression, Logistic
Comments Treatment group was the independent variable in the logistic regression.
6.Secondary Outcome
Title Percentage of Participants With a Sustained Complete Response
Hide Description

The percentage of participants who achieved a sustained complete response, defined as a complete response achieved at Week 48 and Week 96.

Complete response was defined as meeting all of the following criteria:

  1. Urine protein-to-creatinine ratio (UPCR) < 0.5, based on a 24-hour collection;
  2. Estimated glomerular filtration rate (eGFR) ≥120 ml/min/1.73 m^2 calculated by the CKD-EPI formula or, if < 120 ml/min/1.73 m^2, then > 80% of eGFR at entry; and
  3. Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.
Time Frame Week 48, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description

The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.

Confidence intervals were calculated using Clopper-Pearson method.

Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Overall Number of Participants Analyzed 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
26.7
(7.8 to 55.1)
28.6
(8.4 to 58.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 96
Type of Statistical Test Superiority
Comments Treatment group was the independent variable in the logistic regression.
Statistical Test of Hypothesis P-Value 0.91
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
7.Secondary Outcome
Title Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96
Hide Description The percentage of participants who met the criteria for treatment failure, defined by withdrawal from the protocol treatment regimen due to worsening nephritis, infection, or study medication toxicity.
Time Frame Week 24, Week 48 and Week 96
Hide Outcome Measure Data
Hide Analysis Population Description

The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.

Confidence intervals were calculated using Clopper-Pearson method.

Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Overall Number of Participants Analyzed 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 0 to Week 24
18.2
(5.2 to 40.3)
14.3
(3.1 to 36.3)
Week 0 to Week 48
45.5
(24.4 to 67.8)
28.6
(11.3 to 52.2)
Week 0 to Week 96
63.6
(40.7 to 82.8)
47.6
(25.7 to 70.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 0 to Week 24
Type of Statistical Test Superiority
Comments Treatment group was the independent variable in the logistic regression.
Statistical Test of Hypothesis P-Value .73
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 0 to Week 48
Type of Statistical Test Superiority
Comments Treatment group was the independent variable in the logistic regression.
Statistical Test of Hypothesis P-Value 0.26
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 0 to Week 96
Type of Statistical Test Superiority
Comments Treatment group was the independent variable in the logistic regression.
Statistical Test of Hypothesis P-Value 0.29
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
8.Secondary Outcome
Title Count of Participants: Frequency of Non-renal Flares by Week 24
Hide Description Count of participants who experienced non-renal flares, defined as any new "A" finding in a non-renal organ system in the British Isles Lupus Assessment Group (BILAG) assessment. A BILAG "A" finding represents a significant increase in, or a new manifestation of, disease activity.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Overall Number of Participants Analyzed 22 21
Measure Type: Count of Participants
Unit of Measure: Participants
0 Non-renal flares
21
  95.5%
20
  95.2%
1 Non-renal flare
1
   4.5%
0
   0.0%
2 Non-renal flares
0
   0.0%
1
   4.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 0 to Week 24
Type of Statistical Test Superiority
Comments 2 sided test
Statistical Test of Hypothesis P-Value >0.99
Comments 2 sided test
Method Fisher Exact
Comments 2 sided test
9.Secondary Outcome
Title Count of Participants: Frequency of Non-renal Flares by Week 48
Hide Description Count of participants who experienced non-renal flares, defined as any new "A" finding in a non-renal organ system in the British Isles Lupus Assessment Group (BILAG) assessment. A BILAG "A" finding represents a significant increase in, or a new manifestation of, disease activity.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Overall Number of Participants Analyzed 22 21
Measure Type: Count of Participants
Unit of Measure: Participants
0 Non-renal flares
20
  90.9%
20
  95.2%
1 Non-renal flares
2
   9.1%
0
   0.0%
2 Non-renal flare
0
   0.0%
1
   4.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Week 0 to Week 48
Type of Statistical Test Superiority
Comments 2 sided test
Statistical Test of Hypothesis P-Value 0.49
Comments 2 sided test
Method Fisher Exact
Comments 2 sided test
10.Secondary Outcome
Title Count of Participants: Frequency of Non-renal Flares by Week 96
Hide Description Count of participants who experienced non-renal flares, defined as any new "A" finding in a non-renal organ system in the British Isles Lupus Assessment Group (BILAG) assessment. A BILAG "A" finding represents a significant increase in, or a new manifestation of, disease activity.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Overall Number of Participants Analyzed 22 21
Measure Type: Count of Participants
Unit of Measure: Participants
0 Non-renal flares
18
  81.8%
19
  90.5%
1 Non-renal flare
4
  18.2%
1
   4.8%
2 Non-renal flares
0
   0.0%
1
   4.8%
11.Secondary Outcome
Title Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96
Hide Description

The percentage of participants who were anti-double stranded DNA (anti-dsDNA) negative, defined as having anti-dsDNA levels <30 IU/mL.

Anti-dsDNA levels are associated with systemic lupus erythematosus disease activity.

Time Frame Week 24, Week 48 and Week 96
Hide Outcome Measure Data
Hide Analysis Population Description

The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.

Confidence intervals were calculated using Clopper-Pearson method.

Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Overall Number of Participants Analyzed 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 24 Number Analyzed 21 participants 19 participants
14.3
(3.1 to 36.3)
15.8
(3.4 to 39.6)
Week 48 Number Analyzed 20 participants 20 participants
20.0
(5.7 to 43.7)
30.0
(11.9 to 54.3)
Week 96 Number Analyzed 17 participants 18 participants
0.0
(0.0 to 19.5)
27.8
(9.7 to 53.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Treatment group was the independent variable in the logistic regression.
Type of Statistical Test Superiority
Comments 2 sided test
Statistical Test of Hypothesis P-Value 0.89
Comments 2 sided test
Method Regression, Logistic
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Treatment group was the independent variable in the logistic regression.
Type of Statistical Test Superiority
Comments Week 48
Statistical Test of Hypothesis P-Value 0.47
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Treatment group was the independent variable in the logistic regression.
Type of Statistical Test Superiority
Comments Week 96
Statistical Test of Hypothesis P-Value 0.94
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
12.Secondary Outcome
Title Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96
Hide Description

The percentage of participants who were hypocomplementemic for complement component, C3, defined as a C3 level <90 mg/dL.

Serum C3 complement is a protein which can be measured in the blood. Low blood levels of C3 are common in those with active lupus.

Time Frame Week 24, Week 48 and Week 96
Hide Outcome Measure Data
Hide Analysis Population Description

The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.

Confidence intervals were calculated using Clopper-Pearson method.

Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Overall Number of Participants Analyzed 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 24 Number Analyzed 21 participants 20 participants
57.1
(34.0 to 78.2)
30.0
(11.9 to 54.3)
Week 48 Number Analyzed 20 participants 20 participants
55.0
(31.5 to 76.9)
30.0
(11.9 to 54.3)
Week 96 Number Analyzed 18 participants 18 participants
61.1
(35.8 to 82.7)
27.8
(9.7 to 53.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Treatment group was the independent variable in the logistic regression.
Type of Statistical Test Superiority
Comments Week 24
Statistical Test of Hypothesis P-Value 0.08
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Treatment group was the independent variable in the logistic regression.
Type of Statistical Test Superiority
Comments Week 48
Statistical Test of Hypothesis P-Value 0.11
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Treatment group was the independent variable in the logistic regression.
Type of Statistical Test Superiority
Comments Week 96
Statistical Test of Hypothesis P-Value 0.05
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
13.Secondary Outcome
Title Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96
Hide Description

The percentage of participants who were hypocomplementemic for complemen component C4, defined as a C4 level <10 mg/dL.

Serum C4 complement is a protein which can be measured in the blood. Low blood levels of C4 are common in those with active lupus.

Time Frame Week 24, Week 48 and Week 96
Hide Outcome Measure Data
Hide Analysis Population Description

The modified intent-to-treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.

Confidence intervals were calculated using Clopper-Pearson method.

Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
The modified intent to treat population includes all randomized participants who received 1 dose of Solumedrol, 1 dose of rituximab, 1 dose of cyclophosphamide, and, if in the Rituximab/Cyclophosphamide/Belimumab (RCB) arm, 1 dose of belimumab.
Overall Number of Participants Analyzed 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 24 Number Analyzed 21 participants 20 participants
19.0
(5.5 to 41.9)
5.0
(0.1 to 24.9)
Week 48 Number Analyzed 20 participants 20 participants
15.0
(3.2 to 37.9)
15.0
(3.2 to 37.9)
Week 96 Number Analyzed 18 participants 18 participants
16.7
(3.6 to 41.4)
11.1
(1.4 to 34.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Treatment group was the independent variable in the logistic regression.
Type of Statistical Test Superiority
Comments Week 24
Statistical Test of Hypothesis P-Value .20
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Treatment group was the independent variable in the logistic regression.
Type of Statistical Test Superiority
Comments Week 48
Statistical Test of Hypothesis P-Value >0.99
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab/Cyclophosphamide (RC), Rituximab/Cyclophosphamide/Belimumab (RCB)
Comments Treatment group was the independent variable in the logistic regression.
Type of Statistical Test Superiority
Comments Week 96
Statistical Test of Hypothesis P-Value 0.63
Comments 2 sided test
Method Regression, Logistic
Comments 2 sided test
14.Secondary Outcome
Title Frequency of Specific Adverse Events of Interest By Event by Week 96
Hide Description

Number of ≥ Grade 2 specific treatment-emergent adverse events (AEs) of interest. Grade 2 or higher AEs were classified according to the listed categories of interest based on the study team's review of the AEs.

Treatment-emergent AEs are those:

  • with an onset date on or after the first dose of study medication,
  • with onset before first dose but that worsened in severity after first dose, and
  • for which the start of the AE in relation to the start of study medication could not be established.

The severity of AEs was classified using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v4.03: June 14, 2010). AEs were classified by system organ class and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA) version 17.0.

Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population includes all participants who received at least one dose of study treatment.
Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The safety population includes all participants who received at least one dose of study treatment.
The safety population includes all participants who received at least one dose of study treatment.
Overall Number of Participants Analyzed 22 21
Measure Type: Number
Unit of Measure: Events
Any event leading to death 0 0
≥Grade 2 leukopenia or thrombocytopenia 13 16
Premature ovarian failure 0 0
Malignancy 0 0
Venous thromboembolic event 3 0
15.Secondary Outcome
Title Frequency of Specific Adverse Events of Interest By Participant, By Week 96
Hide Description

Number of participants who experienced ≥Grade 2 specific treatment-emergent adverse events (AEs) of interest. Grade 2 or higher AEs were classified according to the listed categories of interest based on the study team's review of the AEs.

Treatment-emergent AEs are those:

  • with an onset date on or after the first dose of study medication,
  • with onset before first dose but that worsened in severity after first dose, and
  • for which the start of the AE in relation to the start of study medication could not be established.

The severity of AEs was classified using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v4.03: June 14, 2010). AEs were classified by system organ class and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA) version 17.0.

Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population includes all participants who received at least one dose of study treatment.
Arm/Group Title Rituximab/Cyclophosphamide (RC) Rituximab/Cyclophosphamide/Belimumab (RCB)
Hide Arm/Group Description:
The safety population includes all participants who received at least one dose of study treatment.
The safety population includes all participants who received at least one dose of study treatment.
Overall Number of Participants Analyzed 22 21
Measure Type: Count of Participants
Unit of Measure: Participants
Any event leading to death
0
   0.0%
0
   0.0%
≥Grade 2 leukopenia or thrombocytopenia
6
  27.3%
6
  28.6%
Premature ovarian failure
0
   0.0%
0
   0.0%
Malignancy
0
   0.0%
0
   0.0%
Venous thromboembolic event
2
   9.1%
0
   0.0%
Time Frame 1 year, 8 months (96 Weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title RC Group on Treatment RCB Group on Treatment RC Group After Treatment Discontinuation RCB Group After Treatment Discontinuation
Hide Arm/Group Description Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone 40 mg per day was administered for the first 2 weeks, with a guided steroid taper to 10mg per day by Week 12 and continued treatment until Week 96. Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone 40 mg per day was administered for the first 2 weeks, with a guided steroid taper to 10mg per day by Week 12 and continued treatment until Week 96. In addition, participants received IV belimumab 10mg/kg at Weeks 4, 6, 8, and then every 4 weeks through Week 48 in addition to prednisone. Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone 40 mg per day was administered for the first 2 weeks, with a guided steroid taper to 10mg per day by Week 12 and continued treatment until Week 96. Participants received infusions of Solumedrol 100mg, rituximab 1000mg, and cyclophosphamide 750mg intravenously (IV) at Week 0 and Week 2. Prednisone 40 mg per day was administered for the first 2 weeks, with a guided steroid taper to 10mg per day by Week 12 and continued treatment until Week 96. In addition, participants received IV belimumab 10mg/kg at Weeks 4, 6, 8, and then every 4 weeks through Week 48 in addition to prednisone.
All-Cause Mortality
RC Group on Treatment RCB Group on Treatment RC Group After Treatment Discontinuation RCB Group After Treatment Discontinuation
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)      0/21 (0.00%)      0/22 (0.00%)      0/21 (0.00%)    
Hide Serious Adverse Events
RC Group on Treatment RCB Group on Treatment RC Group After Treatment Discontinuation RCB Group After Treatment Discontinuation
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/22 (27.27%)      4/21 (19.05%)      8/22 (36.36%)      1/21 (4.76%)    
Blood and lymphatic system disorders         
Anaemia  1  1/22 (4.55%)  1 0/21 (0.00%)  0 1/22 (4.55%)  2 0/21 (0.00%)  0
Pancytopenia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Cardiac disorders         
Aortic valve incompetence  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Atrial fibrillation  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Myocardial ischaemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Eye disorders         
Blindness transient  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Immune system disorders         
Serum sickness  1  0/22 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0 0/21 (0.00%)  0
Infections and infestations         
Abscess soft tissue  1  0/22 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0 0/21 (0.00%)  0
Cellulitis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 1/21 (4.76%)  2
Infective myositis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0 1/21 (4.76%)  1
Mediastinitis  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Pneumonia  1  2/22 (9.09%)  2 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Pneumonia respiratory syncytial viral  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Pseudomonal bacteraemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Sepsis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Staphylococcal bacteraemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Urinary tract infection  1  0/22 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0 0/21 (0.00%)  0
Injury, poisoning and procedural complications         
Tendon rupture  1  0/22 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0 0/21 (0.00%)  0
Investigations         
Blood creatinine increased  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Metabolism and nutrition disorders         
Hypocalcaemia  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Intervertebral disc protrusion  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Osteonecrosis  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Systemic lupus erythematosus  1  2/22 (9.09%)  2 0/21 (0.00%)  0 2/22 (9.09%)  3 0/21 (0.00%)  0
Nervous system disorders         
Grand mal convulsion  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Posterior reversible encephalopathy syndrome  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  2 0/21 (0.00%)  0
Renal and urinary disorders         
Lupus nephritis  1  1/22 (4.55%)  1 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Renal failure  1  0/22 (0.00%)  0 0/21 (0.00%)  0 2/22 (9.09%)  2 0/21 (0.00%)  0
Renal failure acute  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  2 0/21 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Pulmonary alveolar haemorrhage  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Vascular disorders         
Axillary vein thrombosis  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Hypertensive emergency  1  0/22 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  2 0/21 (0.00%)  0
Subclavian vein thrombosis  1  1/22 (4.55%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
1
Term from vocabulary, 17.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
RC Group on Treatment RCB Group on Treatment RC Group After Treatment Discontinuation RCB Group After Treatment Discontinuation
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/22 (100.00%)      21/21 (100.00%)      11/22 (50.00%)      6/21 (28.57%)    
Blood and lymphatic system disorders         
Anaemia  1  10/22 (45.45%)  17 13/21 (61.90%)  20 3/22 (13.64%)  3 1/21 (4.76%)  1
Leukopenia  1  5/22 (22.73%)  10 6/21 (28.57%)  15 2/22 (9.09%)  2 0/21 (0.00%)  0
Lymphopenia  1  17/22 (77.27%)  33 11/21 (52.38%)  19 9/22 (40.91%)  11 3/21 (14.29%)  4
Neutropenia  1  3/22 (13.64%)  5 5/21 (23.81%)  8 2/22 (9.09%)  2 0/21 (0.00%)  0
Endocrine disorders         
Cushingoid  1  2/22 (9.09%)  2 0/21 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Gastrointestinal disorders         
Diarrhoea  1  2/22 (9.09%)  2 2/21 (9.52%)  3 1/22 (4.55%)  1 1/21 (4.76%)  1
Dyspepsia  1  2/22 (9.09%)  2 1/21 (4.76%)  1 0/22 (0.00%)  0 0/21 (0.00%)  0
Nausea  1  5/22 (22.73%)  6 1/21 (4.76%)  1 0/22 (0.00%)  0 0/21 (0.00%)  0
Vomiting  1  0/22 (0.00%)  0 2/21 (9.52%)  3 0/22 (0.00%)  0 0/21 (0.00%)  0
General disorders         
Fatigue  1  2/22 (9.09%)  4 1/21 (4.76%)  1 0/22 (0.00%)  0 0/21 (0.00%)  0
Local swelling  1  0/22 (0.00%)  0 2/21 (9.52%)  2 0/22 (0.00%)  0 1/21 (4.76%)  1
Oedema peripheral  1  3/22 (13.64%)  3 1/21 (4.76%)  1 1/22 (4.55%)  1 0/21 (0.00%)  0
Immune system disorders         
Hypogammaglobulinaemia  1  9/22 (40.91%)  12 11/21 (52.38%)  18 4/22 (18.18%)  5 0/21 (0.00%)  0
Infections and infestations         
Herpes zoster  1  0/22 (0.00%)  0 3/21 (14.29%)  3 0/22 (0.00%)  0 0/21 (0.00%)  0
Nasopharyngitis  1  0/22 (0.00%)  0 2/21 (9.52%)  3 0/22 (0.00%)  0 1/21 (4.76%)  1
Oral candidiasis  1  2/22 (9.09%)  3 2/21 (9.52%)  3 0/22 (0.00%)  0 0/21 (0.00%)  0
Upper respiratory tract infection  1  3/22 (13.64%)  6 1/21 (4.76%)  4 0/22 (0.00%)  0 1/21 (4.76%)  1
Urinary tract infection  1  3/22 (13.64%)  7 1/21 (4.76%)  2 0/22 (0.00%)  0 0/21 (0.00%)  0
Viral upper respiratory tract infection  1  2/22 (9.09%)  2 0/21 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Injury, poisoning and procedural complications         
Infusion related reaction  1  1/22 (4.55%)  1 2/21 (9.52%)  2 0/22 (0.00%)  0 0/21 (0.00%)  0
Maternal exposure during pregnancy  1  0/22 (0.00%)  0 3/21 (14.29%)  4 0/22 (0.00%)  0 0/21 (0.00%)  0
Investigations         
Blood creatinine increased  1  6/22 (27.27%)  9 8/21 (38.10%)  11 1/22 (4.55%)  1 2/21 (9.52%)  2
Metabolism and nutrition disorders         
Hypoalbuminaemia  1  10/22 (45.45%)  15 8/21 (38.10%)  10 2/22 (9.09%)  2 1/21 (4.76%)  2
Musculoskeletal and connective tissue disorders         
Arthralgia  1  2/22 (9.09%)  2 1/21 (4.76%)  1 0/22 (0.00%)  0 0/21 (0.00%)  0
Back pain  1  3/22 (13.64%)  3 1/21 (4.76%)  1 0/22 (0.00%)  0 1/21 (4.76%)  1
Nervous system disorders         
Headache  1  0/22 (0.00%)  0 2/21 (9.52%)  2 1/22 (4.55%)  1 0/21 (0.00%)  0
Psychiatric disorders         
Insomnia  1  2/22 (9.09%)  2 0/21 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Renal and urinary disorders         
Lupus nephritis  1  4/22 (18.18%)  4 6/21 (28.57%)  6 1/22 (4.55%)  1 1/21 (4.76%)  1
Proteinuria  1  7/22 (31.82%)  7 6/21 (28.57%)  8 3/22 (13.64%)  3 1/21 (4.76%)  1
Respiratory, thoracic and mediastinal disorders         
Cough  1  2/22 (9.09%)  2 2/21 (9.52%)  2 0/22 (0.00%)  0 0/21 (0.00%)  0
Dyspnoea  1  2/22 (9.09%)  2 1/21 (4.76%)  1 0/22 (0.00%)  0 0/21 (0.00%)  0
Skin and subcutaneous tissue disorders         
Alopecia  1  2/22 (9.09%)  2 0/21 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Vascular disorders         
Hypertension  1  2/22 (9.09%)  2 1/21 (4.76%)  1 1/22 (4.55%)  2 0/21 (0.00%)  0
1
Term from vocabulary, 17.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Clinical Research Operations Program
Organization: DAIT/NIAID
Phone: 301-594-7669
EMail: DAITClinicalTrialsGov@niaid.nih.gov
Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02260934    
Other Study ID Numbers: DAIT ITN055AI
CALIBRATE ( Other Identifier: Immune Tolerance Network )
First Submitted: October 6, 2014
First Posted: October 9, 2014
Results First Submitted: March 13, 2019
Results First Posted: April 8, 2019
Last Update Posted: March 24, 2020