Lupus Nephritis
Conditions
Brief summary
In this experimental study, researchers will try to find out if treatment of lupus nephritis with a combination of rituximab and cyclophosphamide (CTX), or a combination of rituximab and CTX followed by treatment with belimumab is safe and if this drug combination can block the immune system attacks.
Detailed description
Lupus nephritis is a severe form of systemic lupus erythematosus (SLE) with active disease in the kidneys. SLE is a complex disease in which the body's own immune system attacks some of the body parts: the skin, the joints, the kidneys, the nervous system, the heart, the lungs and the blood. The cause of SLE is not known. Treatment for SLE usually involves drugs that are designed to block the immune system attacks. When SLE affects the kidneys (nephritis), stronger immune suppressing treatment is usually needed. The drugs used in treatment of lupus nephritis often do not cure the disease and can cause serious side effects, including lowering the immune system too much. When the immune system is too low, a person is at a higher risk of getting infections. Therefore, research into new treatments with fewer serious side effects is needed for lupus nephritis.
Interventions
BIOLOGICALRituximab
Rituximab 1000mg intravenously (IV) at week 0 and week 2
DRUGCyclophosphamide
Cyclophosphamide (750 mg) intravenously (IV) at week 0 and week 2.
DRUGPrednisone
* Week 0 and Week 2: Prednisone (40 mg/day; taper to 10 mg/day by week 12) * Continue prednisone 10 mg/day to week 96
DRUGMethylprednisolone
Week 0 and Week 2: Solumedrol (100 mg) IV
DRUGDiphenhydramine
Diphenhydramine (50 mg, or equivalent dose of similar antihistamine) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
DRUGAcetaminophen
Acetaminophen (650 mg) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
BIOLOGICALBelimumab
The RCB Group will receive IV belimumab 10mg/kg at weeks 4, 6, 8, and then every 4 weeks through week 48
Sponsors
Immune Tolerance Network (ITN)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR) criteria. 2. Positive antinuclear antibody (ANA) or positive anti-ds DNA test results at visit -1 or any time within 14 days before visit -1. 3. Active proliferative lupus nephritis, as defined by either of the following: * Kidney biopsy documentation within the last 3 months of International Society of Nephrology/Renal Pathology Society (ISN/RPS) proliferative nephritis: Class III, Class IV, or Class V in combination with Class III or IV. * Active urinary sediment and kidney biopsy documentation within the last 12 months of ISN/RPS proliferative nephritis: Class III, Class IV, or Class V in combination with Class III or IV. Active urinary sediment is defined as any one of the following: * \>5 RBC/hpf in the absence of menses and infection; * \>5 White blood cell per high powered field (WBC/hpf) in the absence of infection; or * Cellular casts limited to RBC or WBC casts. 4. Urine protein-to-creatinine ratio (UPCR) \>1 at study entry based on a 24-hour collection. 5. Ability to provide informed consent.
Exclusion criteria
1. New onset lupus nephritis, defined as lupus nephritis for which the participant has not yet been treated with either mycophenolate mofetil or cyclophosphamide. 2. Neutropenia (absolute neutrophil count \<1500/mm\^3). 3. Thrombocytopenia (platelets \<50,000/mm\^3). 4. Moderately severe anemia (Hgb \< mg/dL). 5. Moderately severe hypogammaglobulinemia (IgG \<450 mg/dL) or Immunoglobulin A (IgA) \<10mg/dL. 6. Positive QuantiFERON -Tuberculosis (TB) Gold test results. 7. Pulmonary fibrotic changes on chest radiograph consistent with prior healed tuberculosis. 8. Active bacterial, viral, fungal, or opportunistic infections. 9. Evidence of infection with human immunodeficiency virus (HIV), hepatitis B (as assessed by HBsAg and anti-HBc) or hepatitis C. 10. Hospitalization for treatment of infections, or parenteral (IV or IM) antibacterials, antivirals, anti-fungals, or anti-parasitic agents within the past 60 days. 11. Chronic infection that is currently being treated with suppressive antibiotic therapy, including but not limited to tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, and atypical mycobacteria. 12. History of significant infection or recurrent infection that, in the investigator's opinion, places the participant at risk by participating in this study. 13. Receipt of a live-attenuated vaccine within 3 months of study enrollment. 14. End-stage renal disease (eGFR \<20 mL/min/1.73m\^2). 15. Concomitant malignancies or a history of malignancy, with the exception of adequately treated basal and squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. 16. History of transplantation. 17. History of primary immunodeficiency. 18. Pregnancy. 19. Breastfeeding. 20. Unwillingness to use an FDA-approved form of birth control (including but not limited to a diaphragm, an intrauterine device, progesterone implants or injections, oral contraceptives, the double-barrier method, or a condom). 21. Use of cyclophosphamide within the past 6 months. 22. Use of anti-Tumor Necrosis Factor (TNF) medication, other biologic medications, or experimental non- biologic therapeutic agents within the past 90 days, or 5 half-lives prior to screening, whichever is greater. 23. Intravenous immunoglobulin (IVIG), plasmapheresis, or leukopheresis within the past 90 days. 24. Use of investigational biologic agent within the past 12 months. 25. Prior treatment with rituximab, belimumab, atacicept, or other biologic B cell therapy. 26. Liver function test \[aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase\] results that are \>=2 times the upper limit of normal. 27. Severe, progressive, or uncontrolled renal, hepatic, hematological,gastrointestinal, pulmonary, cardiac, or neurological disease, either related or unrelated to SLE, with the exception of active lupus nephritis (or, in the investigator's opinion, any other concomitant medical condition that places the participant at risk by participating in this study). 28. Comorbidities requiring corticosteroid therapy, including those which have required three or more courses of systemic corticosteroids within the previous 12 months. 29. Current substance abuse or history of substance abuse within the past year. 30. History of severe allergic or anaphylactic reactions to chimeric or fully human monoclonal antibodies. 31. History of anaphylactic reaction to parenteral administration of contrast agents. 32. Lack of peripheral venous access. 33. History of severe depression or severe psychiatric condition. 34. History of suicidal thoughts within the past 2 months or suicidal behavior within the past 6 months, or a significant suicide risk in the investigator's opinion. 35. Inability to comply with study and follow-up procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96 | Week 0 to Week 96 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96 | Week 24, Week 48 and Week 96 | 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). |
| Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96 | Week 24, Week 48 and Week 96 | 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. |
| Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96 | Week 24, Week 48 and Week 96 | 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. |
| Percentage of Participants With a Sustained Complete Response | Week 48, Week 96 | 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. |
| Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96 | Week 24, Week 48 and Week 96 | 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. |
| Count of Participants: Frequency of Non-renal Flares by Week 24 | Week 24 | 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. |
| Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96 | Week 24, Week 48 and Week 96 | 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. |
| Count of Participants: Frequency of Non-renal Flares by Week 96 | Week 96 | 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. |
| Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96 | Week 24, Week 48 and Week 96 | 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. |
| Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96 | Week 24, Week 48 and Week 96 | 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. |
| Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96 | Week 24, Week 48 and Week 96 | 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. |
| Frequency of Specific Adverse Events of Interest By Event by Week 96 | Week 96 | 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. |
| Frequency of Specific Adverse Events of Interest By Participant, By Week 96 | Week 96 | 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. |
| Count of Participants: Frequency of Non-renal Flares by Week 48 | Week 48 | 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. |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab/Cyclophosphamide (RC) 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. | 22 |
| Rituximab/Cyclophosphamide/Belimumab (RCB) 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. | 21 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Participant Relocated | 1 | 0 |
| Overall Study | Site error | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Rituximab/Cyclophosphamide/Belimumab (RCB) | Total | Rituximab/Cyclophosphamide (RC) |
|---|---|---|---|
| Age, Continuous | 34.5 years STANDARD_DEVIATION 9.1 | 33.4 years STANDARD_DEVIATION 10.3 | 32.3 years STANDARD_DEVIATION 11.4 |
| Anti-Double Stranded DNA (Anti-dsDNA) Positive | 19 Participants | 39 Participants | 20 Participants |
| B Cell Count | 216.0 cells/µL STANDARD_DEVIATION 207.3 | 188.3 cells/µL STANDARD_DEVIATION 183.6 | 160.5 cells/µL STANDARD_DEVIATION 157.4 |
| Duration of Lupus Nephritis | 6.8 Years STANDARD_DEVIATION 6.6 | 5.8 Years STANDARD_DEVIATION 5.7 | 4.8 Years STANDARD_DEVIATION 4.5 |
| Duration of Lupus Nephritis More Than One Year ≤ 1 year | 3 Participants | 7 Participants | 4 Participants |
| Duration of Lupus Nephritis More Than One Year > 1 year | 18 Participants | 36 Participants | 18 Participants |
| Elevated Urine Protein-to-Creatinine Ratio (UPCR) | 8 Participants | 22 Participants | 14 Participants |
| Estimated glomerular filtration rate (eGFR) | 89.1 mL/min/1.73m^2 STANDARD_DEVIATION 33.9 | 90.9 mL/min/1.73m^2 STANDARD_DEVIATION 34.6 | 92.7 mL/min/1.73m^2 STANDARD_DEVIATION 36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 15 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 28 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hypocomplementemic for C3 | 16 Participants | 34 Participants | 18 Participants |
| Hypocomplementemic for C4 | 8 Participants | 18 Participants | 10 Participants |
| Hypogammaglobulinemia | 4 Participants | 6 Participants | 2 Participants |
| Immunoglobulin G (IgG) Level | 1057.1 mg/dL STANDARD_DEVIATION 589.5 | 1050.8 mg/dL STANDARD_DEVIATION 499.1 | 1044.9 mg/dL STANDARD_DEVIATION 408.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 17 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 9 Participants | 16 Participants | 7 Participants |
| Region of Enrollment United States | 21 Participants | 43 Participants | 22 Participants |
| Serum Albumin | 2.9 g/dL STANDARD_DEVIATION 0.6 | 2.9 g/dL STANDARD_DEVIATION 0.6 | 3.0 g/dL STANDARD_DEVIATION 0.5 |
| Serum Creatinine | 1.0 mg/dL STANDARD_DEVIATION 0.5 | 1.0 mg/dL STANDARD_DEVIATION 0.4 | 1.0 mg/dL STANDARD_DEVIATION 0.4 |
| Sex: Female, Male Female | 19 Participants | 37 Participants | 18 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 4 Participants |
| Urine Protein-to-Creatinine Ratio (UPCR) from 24 Hour Collection | 3.3 Ratio STANDARD_DEVIATION 2.5 | 3.4 Ratio STANDARD_DEVIATION 2 | 3.4 Ratio STANDARD_DEVIATION 1.5 |
| Weight | 75.4 kg STANDARD_DEVIATION 26 | 72.5 kg STANDARD_DEVIATION 22.2 | 69.7 kg STANDARD_DEVIATION 18 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 21 | 0 / 22 | 0 / 21 |
| other Total, other adverse events | 22 / 22 | 21 / 21 | 11 / 22 | 6 / 21 |
| serious Total, serious adverse events | 6 / 22 | 4 / 21 | 8 / 22 | 1 / 21 |
Outcome results
Primary
Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96 | Week 0 to Week 24 | 9.1 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96 | Week 0 to Week 48 | 22.7 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96 | Week 0 to Week 96 | 27.3 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96 | Week 0 to Week 24 | 4.8 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96 | Week 0 to Week 48 | 9.5 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96 | Week 0 to Week 96 | 9.5 percentage of participants |
Comparison: Week 0 to Week 24p-value: 0.58Regression, Logistic
Comparison: Week 0 to Week 48p-value: 0.25Regression, Logistic
Comparison: Week 0 to Week 96.p-value: 0.15Regression, Logistic
Secondary
Count of Participants: Frequency of Non-renal Flares by Week 24
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Count of Participants: Frequency of Non-renal Flares by Week 24 | 0 Non-renal flares | 21 Participants |
| Rituximab/Cyclophosphamide (RC) | Count of Participants: Frequency of Non-renal Flares by Week 24 | 1 Non-renal flare | 1 Participants |
| Rituximab/Cyclophosphamide (RC) | Count of Participants: Frequency of Non-renal Flares by Week 24 | 2 Non-renal flares | 0 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Count of Participants: Frequency of Non-renal Flares by Week 24 | 0 Non-renal flares | 20 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Count of Participants: Frequency of Non-renal Flares by Week 24 | 2 Non-renal flares | 1 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Count of Participants: Frequency of Non-renal Flares by Week 24 | 1 Non-renal flare | 0 Participants |
Comparison: Week 0 to Week 24p-value: >0.99Fisher Exact
Secondary
Count of Participants: Frequency of Non-renal Flares by Week 48
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Count of Participants: Frequency of Non-renal Flares by Week 48 | 0 Non-renal flares | 20 Participants |
| Rituximab/Cyclophosphamide (RC) | Count of Participants: Frequency of Non-renal Flares by Week 48 | 1 Non-renal flares | 2 Participants |
| Rituximab/Cyclophosphamide (RC) | Count of Participants: Frequency of Non-renal Flares by Week 48 | 2 Non-renal flare | 0 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Count of Participants: Frequency of Non-renal Flares by Week 48 | 0 Non-renal flares | 20 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Count of Participants: Frequency of Non-renal Flares by Week 48 | 1 Non-renal flares | 0 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Count of Participants: Frequency of Non-renal Flares by Week 48 | 2 Non-renal flare | 1 Participants |
Comparison: Week 0 to Week 48p-value: 0.49Fisher Exact
Secondary
Count of Participants: Frequency of Non-renal Flares by Week 96
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Count of Participants: Frequency of Non-renal Flares by Week 96 | 0 Non-renal flares | 18 Participants |
| Rituximab/Cyclophosphamide (RC) | Count of Participants: Frequency of Non-renal Flares by Week 96 | 1 Non-renal flare | 4 Participants |
| Rituximab/Cyclophosphamide (RC) | Count of Participants: Frequency of Non-renal Flares by Week 96 | 2 Non-renal flares | 0 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Count of Participants: Frequency of Non-renal Flares by Week 96 | 0 Non-renal flares | 19 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Count of Participants: Frequency of Non-renal Flares by Week 96 | 1 Non-renal flare | 1 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Count of Participants: Frequency of Non-renal Flares by Week 96 | 2 Non-renal flares | 1 Participants |
Secondary
Frequency of Specific Adverse Events of Interest By Event by Week 96
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
Population: The safety population includes all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Frequency of Specific Adverse Events of Interest By Event by Week 96 | ≥Grade 2 leukopenia or thrombocytopenia | 13 Events |
| Rituximab/Cyclophosphamide (RC) | Frequency of Specific Adverse Events of Interest By Event by Week 96 | Malignancy | 0 Events |
| Rituximab/Cyclophosphamide (RC) | Frequency of Specific Adverse Events of Interest By Event by Week 96 | Premature ovarian failure | 0 Events |
| Rituximab/Cyclophosphamide (RC) | Frequency of Specific Adverse Events of Interest By Event by Week 96 | Venous thromboembolic event | 3 Events |
| Rituximab/Cyclophosphamide (RC) | Frequency of Specific Adverse Events of Interest By Event by Week 96 | Any event leading to death | 0 Events |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Frequency of Specific Adverse Events of Interest By Event by Week 96 | Venous thromboembolic event | 0 Events |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Frequency of Specific Adverse Events of Interest By Event by Week 96 | Any event leading to death | 0 Events |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Frequency of Specific Adverse Events of Interest By Event by Week 96 | ≥Grade 2 leukopenia or thrombocytopenia | 16 Events |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Frequency of Specific Adverse Events of Interest By Event by Week 96 | Premature ovarian failure | 0 Events |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Frequency of Specific Adverse Events of Interest By Event by Week 96 | Malignancy | 0 Events |
Secondary
Frequency of Specific Adverse Events of Interest By Participant, By Week 96
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
Population: The safety population includes all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Frequency of Specific Adverse Events of Interest By Participant, By Week 96 | ≥Grade 2 leukopenia or thrombocytopenia | 6 Participants |
| Rituximab/Cyclophosphamide (RC) | Frequency of Specific Adverse Events of Interest By Participant, By Week 96 | Malignancy | 0 Participants |
| Rituximab/Cyclophosphamide (RC) | Frequency of Specific Adverse Events of Interest By Participant, By Week 96 | Premature ovarian failure | 0 Participants |
| Rituximab/Cyclophosphamide (RC) | Frequency of Specific Adverse Events of Interest By Participant, By Week 96 | Venous thromboembolic event | 2 Participants |
| Rituximab/Cyclophosphamide (RC) | Frequency of Specific Adverse Events of Interest By Participant, By Week 96 | Any event leading to death | 0 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Frequency of Specific Adverse Events of Interest By Participant, By Week 96 | Venous thromboembolic event | 0 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Frequency of Specific Adverse Events of Interest By Participant, By Week 96 | Any event leading to death | 0 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Frequency of Specific Adverse Events of Interest By Participant, By Week 96 | ≥Grade 2 leukopenia or thrombocytopenia | 6 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Frequency of Specific Adverse Events of Interest By Participant, By Week 96 | Premature ovarian failure | 0 Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Frequency of Specific Adverse Events of Interest By Participant, By Week 96 | Malignancy | 0 Participants |
Secondary
Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96 | Week 24 | 57.1 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96 | Week 48 | 55.0 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96 | Week 96 | 61.1 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96 | Week 24 | 30.0 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96 | Week 48 | 30.0 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96 | Week 96 | 27.8 percentage of participants |
Comparison: Treatment group was the independent variable in the logistic regression.p-value: 0.08Regression, Logistic
Comparison: Treatment group was the independent variable in the logistic regression.p-value: 0.11Regression, Logistic
Comparison: Treatment group was the independent variable in the logistic regression.p-value: 0.05Regression, Logistic
Secondary
Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96 | Week 24 | 19.0 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96 | Week 48 | 15.0 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96 | Week 96 | 16.7 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96 | Week 24 | 5.0 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96 | Week 48 | 15.0 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96 | Week 96 | 11.1 percentage of participants |
Comparison: Treatment group was the independent variable in the logistic regression.p-value: 0.2Regression, Logistic
Comparison: Treatment group was the independent variable in the logistic regression.p-value: >0.99Regression, Logistic
Comparison: Treatment group was the independent variable in the logistic regression.p-value: 0.63Regression, Logistic
Secondary
Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96 | Week 24 | 23.8 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96 | Week 48 | 35.0 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96 | Week 96 | 33.3 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96 | Week 24 | 30.0 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96 | Week 48 | 42.1 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96 | Week 96 | 42.9 percentage of participants |
Comparison: Week 24p-value: 0.66Regression, Logistic
Comparison: Week 48p-value: 0.65Regression, Logistic
Secondary
Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96 | Week 24 | 14.3 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96 | Week 48 | 20.0 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96 | Week 96 | 0.0 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96 | Week 24 | 15.8 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96 | Week 48 | 30.0 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96 | Week 96 | 27.8 percentage of participants |
Comparison: Treatment group was the independent variable in the logistic regression.p-value: 0.89Regression, Logistic
Comparison: Treatment group was the independent variable in the logistic regression.p-value: 0.47Regression, Logistic
Comparison: Treatment group was the independent variable in the logistic regression.p-value: 0.94Regression, Logistic
Secondary
Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96 | Week 24 | 46.7 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96 | Week 48 | 60.0 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96 | Week 96 | 53.3 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96 | Week 24 | 55.0 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96 | Week 48 | 73.7 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96 | Week 96 | 71.4 percentage of participants |
Comparison: Week 24 Treatment group was the independent variable in the logistic regression.p-value: 0.64Regression, Logistic
Comparison: Week 48p-value: 0.37Regression, Logistic
Comparison: Week 96p-value: 0.32Regression, Logistic
Secondary
Percentage of Participants With a Sustained Complete Response
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With a Sustained Complete Response | 26.7 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With a Sustained Complete Response | 28.6 percentage of participants |
Comparison: Week 96p-value: 0.91Regression, Logistic
Secondary
Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96 | Week 24 | 31.3 Percentage of Participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96 | Week 48 | 35.7 Percentage of Participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96 | Week 96 | 40.0 Percentage of Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96 | Week 24 | 6.3 Percentage of Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96 | Week 48 | 11.8 Percentage of Participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96 | Week 96 | 30.8 Percentage of Participants |
Secondary
Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96 | Week 0 to Week 24 | 0 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96 | Week 0 to Week 48 | 0 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96 | Week 0 to Week 96 | 0 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96 | Week 0 to Week 24 | 0 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96 | Week 0 to Week 48 | 0 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96 | Week 0 to Week 96 | 0 percentage of participants |
Comparison: Week 0 to Week 24Regression, Logistic
Comparison: Week 0 to Week 48Regression, Logistic
Comparison: 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.Regression, Logistic
Secondary
Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96 | Week 0 to Week 24 | 18.2 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96 | Week 0 to Week 48 | 45.5 percentage of participants |
| Rituximab/Cyclophosphamide (RC) | Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96 | Week 0 to Week 96 | 63.6 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96 | Week 0 to Week 24 | 14.3 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96 | Week 0 to Week 48 | 28.6 percentage of participants |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96 | Week 0 to Week 96 | 47.6 percentage of participants |
Comparison: Week 0 to Week 24p-value: 0.73Regression, Logistic
Comparison: Week 0 to Week 48p-value: 0.26Regression, Logistic
Comparison: Week 0 to Week 96p-value: 0.29Regression, Logistic