CALIBRATE: Rituximab and Belimumab for Lupus Nephritis

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02260934
• Collaborator: Immune Tolerance Network (ITN) (Other)
• Enrollment: 43
• Locations: 15
• Arms: 2
• Actual Duration (Months): 43
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lupus Nephritis	Biological: Rituximab; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Methylprednisolone; Drug: Diphenhydramine; Drug: Acetaminophen; Biological: Rituximab; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Methylprednisolone; Drug: Diphenhydramine; Drug: Acetaminophen; Biological: Belimumab	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis (ITN055AI)
• Actual Study Start Date: Jul 9, 2015
• Actual Primary Completion Date: Mar 12, 2018
• Actual Study Completion Date: Feb 8, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Rituximab/Cyclophosphamide (RC) Prednisone taper to 10 mg/day by week 12 and continue prednisone 10 mg/day to week 96.	Biological: Rituximab; Rituximab 1000mg intravenously (IV) at week 0 and week 2; Other Names: Rituxan ; Drug: Cyclophosphamide; Cyclophosphamide (750 mg) intravenously (IV) at week 0 and week 2.; Other Names: Cytoxan ; Drug: Prednisone; 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; Other Names: Deltasone ; Drug: Methylprednisolone; Week 0 and Week 2: Solumedrol (100 mg) IV; Other Names: Solu-Medrol ; Drug: Diphenhydramine; 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.; Drug: Acetaminophen; Acetaminophen (650 mg) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.; Other Names: Tylenol
Experimental: Rituximab/Cyclophosphamide/Belimumab (RCB) Belimumab (10 mg/kg IV) at weeks 4, 6, 8, and every 4 weeks to week 48. Prednisone taper to 10 mg/day by week 12, and continue prednisone 10 mg/day to week 96.	Biological: Rituximab; Rituximab 1000mg intravenously (IV) at week 0 and week 2.; Other Names: Rituxan ; Drug: Cyclophosphamide; Cyclophosphamide (750 mg) intravenously (IV) at week 0 and week 2.; Other Names: Cytoxan ; Drug: Prednisone; 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; Other Names: Deltasone ; Drug: Methylprednisolone; Week 0 and Week 2: Solumedrol (100 mg) IV; Other Names: Solu-Medrol ; Drug: Diphenhydramine; 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.; Drug: Acetaminophen; Acetaminophen (650 mg) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.; Other Names: Tylenol ; Biological: Belimumab; The RCB Group will receive IV belimumab 10mg/kg at weeks 4, 6, 8, and then every 4 weeks through week 48; Other Names: Benlysta

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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).

3. 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: Urine protein-to-creatinine ratio (UPCR) < 0.5, based on a 24-hour collection; 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 Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.

4. 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: >50% improvement in the urine protein-to-creatinine ratio (UPCR) from study entry, based on a 24-hour collection; 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 Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.

5. 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: Urine protein-to-creatinine ratio (UPCR) < 0.5, based on a 24-hour collection; 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 Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

1. Urine protein-to-creatinine ratio (UPCR) >1 at study entry based on a 24-hour collection.

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama, Birmingham	Birmingham	Alabama	United States	35294
2	UCLA Medical Center: Division of Rheumatology	Los Angeles	California	United States	90095
3	University of California, San Francisco	San Francisco	California	United States	94143
4	University of Colorado Denver: School of Medicine: Division of Rheumatology	Aurora	Colorado	United States	80045
5	Colorado Kidney Care	Denver	Colorado	United States	80218
6	Emory University School of Medicine	Atlanta	Georgia	United States	30303
7	Washington University in St. Louis	Saint Louis	Missouri	United States	36110
8	Feinstein Institute, North Shore Hospital	Manhasset	New York	United States	10030
9	New York University, Langone Medical Center	New York	New York	United States	10016
10	Weill Cornell Medical College: Hospital for Special Surgery -	New York	New York	United States	10021
11	Columbia University Medical Center	New York	New York	United States	10032
12	University of North Carolina School of Medicine:	Chapel Hill	North Carolina	United States	27599
13	Ohio State University Wexner Medical Center:	Columbus	Ohio	United States	43213
14	Medical University of South Carolina	Charleston	South Carolina	United States	29425
15	University of Texas Southwestern	Dallas	Texas	United States	75390

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Immune Tolerance Network (ITN)

Investigators

• Study Chair: Betty Diamond, M.D., Feinstein Institute for Medical Research
• Study Chair: David Wofsy, M.D., University of California San Francisco, Department of Medicine
• Study Chair: Maria Dall'Era, M.D., University of California San Francisco, Department of Medicine
• Study Chair: Cynthia Aranow, M.D., Feinstein Institute for Medical Research

Study Documents (Full-Text)

• Study Protocol - Oct 9, 2015
• Statistical Analysis Plan - May 7, 2018

More Information

Additional Information:

• National Institute of Allergy and Infectious Diseases website
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Immune Tolerance Network (ITN) website
• ITN CALIBRATE study website

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT02260934
• Other Study ID Numbers: DAIT ITN055AI; CALIBRATE
• First Posted: Oct 9, 2014
• Last Update Posted: Dec 1, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Nephritis; Lupus Nephritis; Acetaminophen; Diphenhydramine; Promethazine; Prednisone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Rituximab; Belimumab; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

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 Detail	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)
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	17
NOT COMPLETED	3	4

Baseline Characteristics

Arm/Group Title	Rituximab/Cyclophosphamide (RC)	Rituximab/Cyclophosphamide/Belimumab (RCB)	Total
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 Participants	22	21	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.3 (11.4)	34.5 (9.1)	33.4 (10.3)
Sex: Female, Male (Count of Participants)
Female	18 81.8%	19 90.5%	37 86%
Male	4 18.2%	2 9.5%	6 14%
Ethnicity (NIH/OMB) (Count of 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%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	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%
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%
Region of Enrollment (Count of Participants)
United States	22 100%	21 100%	43 100%
Urine Protein-to-Creatinine Ratio (UPCR) from 24 Hour Collection (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	3.4 (1.5)	3.3 (2.5)	3.4 (2.0)
Elevated Urine Protein-to-Creatinine Ratio (UPCR) (Count of Participants)
Count of Participants [Participants]	14 63.6%	8 38.1%	22 51.2%
Serum Creatinine (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1.0 (0.4)	1.0 (0.5)	1.0 (0.4)
Estimated glomerular filtration rate (eGFR) (mL/min/1.73m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min/1.73m^2]	92.7 (36.0)	89.1 (33.9)	90.9 (34.6)
Serum Albumin (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	3.0 (0.5)	2.9 (0.6)	2.9 (0.6)
B Cell Count (cells/µL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/µL]	160.5 (157.4)	216.0 (207.3)	188.3 (183.6)
Immunoglobulin G (IgG) Level (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1044.9 (408.9)	1057.1 (589.5)	1050.8 (499.1)
Hypogammaglobulinemia (Count of Participants)
Count of Participants [Participants]	2 9.1%	4 19%	6 14%
Anti-Double Stranded DNA (Anti-dsDNA) Positive (Count of Participants)
Count of Participants [Participants]	20 90.9%	19 90.5%	39 90.7%
Hypocomplementemic for C3 (Count of Participants)
Count of Participants [Participants]	18 81.8%	16 76.2%	34 79.1%
Hypocomplementemic for C4 (Count of Participants)
Count of Participants [Participants]	10 45.5%	8 38.1%	18 41.9%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	69.7 (18.0)	75.4 (26.0)	72.5 (22.2)
Duration of Lupus Nephritis (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	4.8 (4.5)	6.8 (6.6)	5.8 (5.7)
Duration of Lupus Nephritis More Than One Year (Count of Participants)
> 1 year	18 81.8%	18 85.7%	36 83.7%
≤ 1 year	4 18.2%	3 14.3%	7 16.3%

Outcome Measures

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
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
Week 0 to Week 24	9.1 41.4%	4.8 22.9%
Week 0 to Week 48	22.7 103.2%	9.5 45.2%
Week 0 to Week 96	27.3 124.1%	9.5 45.2%

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
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.

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
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.

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
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
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
Week 24	31.3 142.3%	6.3 30%
Week 48	35.7 162.3%	11.8 56.2%
Week 96	40.0 181.8%	30.8 146.7%

3. Secondary Outcome

Title	Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
Week 0 to Week 24	0 0%	0 0%
Week 0 to Week 48	0 0%	0 0%
Week 0 to Week 96	0 0%	0 0%

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
	Comments
	Method
	Comments
Other Statistical Analysis		Treatment group was the independent variable in the logistic regression.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		P-value could not be produced because of zero count in at least one of the treatment arms.

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
	Comments
	Method
	Comments
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
Description	The percentage of participants who achieved a complete response, defined as meeting all of the following criteria: Urine protein-to-creatinine ratio (UPCR) < 0.5, based on a 24-hour collection; 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 Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.
Time Frame	Week 24, Week 48 and Week 96

Outcome Measure Data

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)
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.
Measure Participants	22	21
Week 24	23.8 108.2%	30.0 142.9%
Week 48	35.0 159.1%	42.1 200.5%
Week 96	33.3 151.4%	42.9 204.3%

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

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
Description	The percentage of participants who achieved an overall response, defined as meeting all of the following criteria: >50% improvement in the urine protein-to-creatinine ratio (UPCR) from study entry, based on a 24-hour collection; 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 Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.
Time Frame	Week 24, Week 48 and Week 96

Outcome Measure Data

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)
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.
Measure Participants	22	21
Week 24	46.7 212.3%	55.0 261.9%
Week 48	60.0 272.7%	73.7 351%
Week 96	53.3 242.3%	71.4 340%

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.

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.

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
	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
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: Urine protein-to-creatinine ratio (UPCR) < 0.5, based on a 24-hour collection; 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 Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.
Time Frame	Week 48, Week 96

Outcome Measure Data

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)
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.
Measure Participants	22	21
Number (95% Confidence Interval) [percentage of participants]	26.7 121.4%	28.6 136.2%

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
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
Week 0 to Week 24	18.2 82.7%	14.3 68.1%
Week 0 to Week 48	45.5 206.8%	28.6 136.2%
Week 0 to Week 96	63.6 289.1%	47.6 226.7%

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

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

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
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
0 Non-renal flares	21 95.5%	20 95.2%
1 Non-renal flare	1 4.5%	0 0%
2 Non-renal flares	0 0%	1 4.8%

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
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
0 Non-renal flares	20 90.9%	20 95.2%
1 Non-renal flares	2 9.1%	0 0%
2 Non-renal flare	0 0%	1 4.8%

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
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
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%	1 4.8%

11. Secondary Outcome

Title	Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
Week 24	14.3 65%	15.8 75.2%
Week 48	20.0 90.9%	30.0 142.9%
Week 96	0.0 0%	27.8 132.4%

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

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

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
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
Week 24	57.1 259.5%	30.0 142.9%
Week 48	55.0 250%	30.0 142.9%
Week 96	61.1 277.7%	27.8 132.4%

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

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

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
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
Week 24	19.0 86.4%	5.0 23.8%
Week 48	15.0 68.2%	15.0 71.4%
Week 96	16.7 75.9%	11.1 52.9%

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

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

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
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
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
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

Outcome Measure Data

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)
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.
Measure Participants	22	21
Any event leading to death	0 0%	0 0%
≥Grade 2 leukopenia or thrombocytopenia	6 27.3%	6 28.6%
Premature ovarian failure	0 0%	0 0%
Malignancy	0 0%	0 0%
Venous thromboembolic event	2 9.1%	0 0%

Adverse Events

Time Frame	1 year, 8 months (96 Weeks)
Arm/Group Title	RC Group on Treatment		RCB Group on Treatment		RC Group After Treatment Discontinuation		RCB Group After Treatment Discontinuation
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/21 (0%)		0/22 (0%)		0/21 (0%)
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 (27.3%)		4/21 (19%)		8/22 (36.4%)		1/21 (4.8%)
Blood and lymphatic system disorders
Anaemia	1/22 (4.5%)	1	0/21 (0%)	0	1/22 (4.5%)	2	0/21 (0%)	0
Pancytopenia	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Cardiac disorders
Aortic valve incompetence	1/22 (4.5%)	1	0/21 (0%)	0	0/22 (0%)	0	0/21 (0%)	0
Atrial fibrillation	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Myocardial ischaemia	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Eye disorders
Blindness transient	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Immune system disorders
Serum sickness	0/22 (0%)	0	1/21 (4.8%)	1	0/22 (0%)	0	0/21 (0%)	0
Infections and infestations
Abscess soft tissue	0/22 (0%)	0	1/21 (4.8%)	1	0/22 (0%)	0	0/21 (0%)	0
Cellulitis	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	1/21 (4.8%)	2
Infective myositis	0/22 (0%)	0	0/21 (0%)	0	0/22 (0%)	0	1/21 (4.8%)	1
Mediastinitis	1/22 (4.5%)	1	0/21 (0%)	0	0/22 (0%)	0	0/21 (0%)	0
Pneumonia	2/22 (9.1%)	2	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Pneumonia respiratory syncytial viral	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Pseudomonal bacteraemia	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Sepsis	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Staphylococcal bacteraemia	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Urinary tract infection	0/22 (0%)	0	1/21 (4.8%)	1	0/22 (0%)	0	0/21 (0%)	0
Injury, poisoning and procedural complications
Tendon rupture	0/22 (0%)	0	1/21 (4.8%)	1	0/22 (0%)	0	0/21 (0%)	0
Investigations
Blood creatinine increased	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Metabolism and nutrition disorders
Hypocalcaemia	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Osteonecrosis	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Systemic lupus erythematosus	2/22 (9.1%)	2	0/21 (0%)	0	2/22 (9.1%)	3	0/21 (0%)	0
Nervous system disorders
Grand mal convulsion	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Posterior reversible encephalopathy syndrome	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	2	0/21 (0%)	0
Renal and urinary disorders
Lupus nephritis	1/22 (4.5%)	1	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Renal failure	0/22 (0%)	0	0/21 (0%)	0	2/22 (9.1%)	2	0/21 (0%)	0
Renal failure acute	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	2	0/21 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary alveolar haemorrhage	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0
Vascular disorders
Axillary vein thrombosis	1/22 (4.5%)	1	0/21 (0%)	0	0/22 (0%)	0	0/21 (0%)	0
Hypertensive emergency	0/22 (0%)	0	0/21 (0%)	0	1/22 (4.5%)	2	0/21 (0%)	0
Subclavian vein thrombosis	1/22 (4.5%)	1	0/21 (0%)	0	0/22 (0%)	0	0/21 (0%)	0
Other (Not Including 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	22/22 (100%)		21/21 (100%)		11/22 (50%)		6/21 (28.6%)
Blood and lymphatic system disorders
Anaemia	10/22 (45.5%)	17	13/21 (61.9%)	20	3/22 (13.6%)	3	1/21 (4.8%)	1
Leukopenia	5/22 (22.7%)	10	6/21 (28.6%)	15	2/22 (9.1%)	2	0/21 (0%)	0
Lymphopenia	17/22 (77.3%)	33	11/21 (52.4%)	19	9/22 (40.9%)	11	3/21 (14.3%)	4
Neutropenia	3/22 (13.6%)	5	5/21 (23.8%)	8	2/22 (9.1%)	2	0/21 (0%)	0
Endocrine disorders
Cushingoid	2/22 (9.1%)	2	0/21 (0%)	0	0/22 (0%)	0	0/21 (0%)	0
Gastrointestinal disorders
Diarrhoea	2/22 (9.1%)	2	2/21 (9.5%)	3	1/22 (4.5%)	1	1/21 (4.8%)	1
Dyspepsia	2/22 (9.1%)	2	1/21 (4.8%)	1	0/22 (0%)	0	0/21 (0%)	0
Nausea	5/22 (22.7%)	6	1/21 (4.8%)	1	0/22 (0%)	0	0/21 (0%)	0
Vomiting	0/22 (0%)	0	2/21 (9.5%)	3	0/22 (0%)	0	0/21 (0%)	0
General disorders
Fatigue	2/22 (9.1%)	4	1/21 (4.8%)	1	0/22 (0%)	0	0/21 (0%)	0
Local swelling	0/22 (0%)	0	2/21 (9.5%)	2	0/22 (0%)	0	1/21 (4.8%)	1
Oedema peripheral	3/22 (13.6%)	3	1/21 (4.8%)	1	1/22 (4.5%)	1	0/21 (0%)	0
Immune system disorders
Hypogammaglobulinaemia	9/22 (40.9%)	12	11/21 (52.4%)	18	4/22 (18.2%)	5	0/21 (0%)	0
Infections and infestations
Herpes zoster	0/22 (0%)	0	3/21 (14.3%)	3	0/22 (0%)	0	0/21 (0%)	0
Nasopharyngitis	0/22 (0%)	0	2/21 (9.5%)	3	0/22 (0%)	0	1/21 (4.8%)	1
Oral candidiasis	2/22 (9.1%)	3	2/21 (9.5%)	3	0/22 (0%)	0	0/21 (0%)	0
Upper respiratory tract infection	3/22 (13.6%)	6	1/21 (4.8%)	4	0/22 (0%)	0	1/21 (4.8%)	1
Urinary tract infection	3/22 (13.6%)	7	1/21 (4.8%)	2	0/22 (0%)	0	0/21 (0%)	0
Viral upper respiratory tract infection	2/22 (9.1%)	2	0/21 (0%)	0	0/22 (0%)	0	0/21 (0%)	0
Injury, poisoning and procedural complications
Infusion related reaction	1/22 (4.5%)	1	2/21 (9.5%)	2	0/22 (0%)	0	0/21 (0%)	0
Maternal exposure during pregnancy	0/22 (0%)	0	3/21 (14.3%)	4	0/22 (0%)	0	0/21 (0%)	0
Investigations
Blood creatinine increased	6/22 (27.3%)	9	8/21 (38.1%)	11	1/22 (4.5%)	1	2/21 (9.5%)	2
Metabolism and nutrition disorders
Hypoalbuminaemia	10/22 (45.5%)	15	8/21 (38.1%)	10	2/22 (9.1%)	2	1/21 (4.8%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	2/22 (9.1%)	2	1/21 (4.8%)	1	0/22 (0%)	0	0/21 (0%)	0
Back pain	3/22 (13.6%)	3	1/21 (4.8%)	1	0/22 (0%)	0	1/21 (4.8%)	1
Nervous system disorders
Headache	0/22 (0%)	0	2/21 (9.5%)	2	1/22 (4.5%)	1	0/21 (0%)	0
Psychiatric disorders
Insomnia	2/22 (9.1%)	2	0/21 (0%)	0	0/22 (0%)	0	0/21 (0%)	0
Renal and urinary disorders
Lupus nephritis	4/22 (18.2%)	4	6/21 (28.6%)	6	1/22 (4.5%)	1	1/21 (4.8%)	1
Proteinuria	7/22 (31.8%)	7	6/21 (28.6%)	8	3/22 (13.6%)	3	1/21 (4.8%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/22 (9.1%)	2	2/21 (9.5%)	2	0/22 (0%)	0	0/21 (0%)	0
Dyspnoea	2/22 (9.1%)	2	1/21 (4.8%)	1	0/22 (0%)	0	0/21 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	2/22 (9.1%)	2	0/21 (0%)	0	0/22 (0%)	0	0/21 (0%)	0
Vascular disorders
Hypertension	2/22 (9.1%)	2	1/21 (4.8%)	1	1/22 (4.5%)	2	0/21 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

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.