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CompletedNCT01610492Updated Oct 13, 2017Results posted

A Study of Belimumab in Idiopathic Membranous Glomerulonephropathy

A Phase 2 interventional study of belimumab in Glomerulonephritis, Membranous, sponsored by GlaxoSmithKline. Completed at 8 sites in United Kingdom. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2017-10-13.

Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
14
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study summary

This is a phase II, open label, experimental medicine study to evaluate the efficacy, safety and mechanism of action of belimumab in subjects with antiphospholipase A2 receptor (PLA2R) autoantibody positive idiopathic membranous glomerulonephropathy (IMGN), and to profile the relationship between biomarkers, autoantibody status and clinical response. 10 milligrams per kilogram (mg/kg) belimumab intravenous (IV) will be administered at weeks 0, 2, and then every 4 weeks, over a 24-week treatment period in subjects with anti-PLA2R antibody positive IMGN followed by a further long term treatment period until subjects reach remission of proteinuria, up to a maximum of 2 years total treatment. All subjects will receive background supportive therapy throughout the study. The dosing frequency will be adjusted to every 2 weeks if the subject's proteinuria as assessed by urinary protein creatinine ratio (PCR) is greater than 1000 milligrams per millimole (mg/mmol) [greater than 10 grams(g)/24 hours (h)], to compensate for loss of belimumab in the urine. Effects on mechanistic markers will be measured by the level of proteinuria, levels of anti-PLA2R antibodies, and various other measures of kidney function. These will be compared to historical data. The pharmacokinetics of belimumab will be measured to confirm dosing in heavily proteinuric subjects. Pharmacodynamic (PD) markers, biomarkers and Quality of Life(QoL) in IMGN subjects will also be investigated. Safety will be assessed by adverse events (AE), clinical laboratory evaluations, and vital signs.

02

Conditions studied

  • Glomerulonephritis, Membranous

Keywords

  • IMGN
  • anti-PLA2R antibodies
  • pharmacokinetics
  • belimumab
  • Benlysta
  • Idiopathic Membranous Glomerulonephropathy
  • safety
  • GSK1550188
  • Lymphostat-B
  • membrane attack complex
03

In context

Glomerulonephritis

149 studies on the registry are indexed under Glomerulonephritis; 38 are open to participants now.

This study's enrollment of 14 is below the median of 40 across 112 interventional studies indexed under Glomerulonephritis.

Browse Glomerulonephritis studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age \& Gender: Male or female between 18 and 75 years of age inclusive, at the time of signing the informed consent.
  • Histological diagnosis: Have clinical diagnosis of IMGN, as verified by biopsy (either by light microscope with immuno-fluorescence, or by electron microscope) in the last 7 years with non-active disease >3 years (non-active defined as subject not on immunosuppressants and proteinuria \<2g per 24h) (biopsy results and slides should be available for independent evaluation).
  • Autoantibody: Have positive anti-PLA2R autoantibody test results at screening.
  • Proteinuria: Have clinically active disease (nephrotic range proteinuria) for at least 3 months prior to screening and no improvement (less than 30% reduction), despite supportive therapy (which should include maximal tolerated doses of ACE inhibitor or ARB unless contraindicated, and may include statins, diuretics, dietary salt restriction). During screening proteinuria must be greater than 400mg/mmol by PCR (or greater than 4.0g per 24h) as measured from a 24 h urine collection and/or spot urine sample (early morning where possible) on 2 occasions at least 7 days apart.
  • Female Subjects: A female subject is eligible to participate if she is not pregnant or nursing and at least one of the following conditions apply: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) greater than 40 Milli-International Units per millilitre(MlU/mL) and estradiol less than 40 picograms per milliliter (less than 147 picomoles per liter) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT.

Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. Child-bearing potential and agrees to use one of the contraception methods listed in the protocol for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 16 weeks after the last dose

Exclusion criteria

Exclusion Criteria:

  • Non-Idiopathic membranous glomerulonephropathy (MGN) or other condition affecting the kidney: If the diagnosis of MGN is secondary to other conditions, or the subject has renal impairment from a condition that is not MGN.
  • Severely reduced or deteriorating kidney function: An eGFR at screening \< 40 millilitres (mL) /minute (min) /1.73 meter (m)\^2 (as determined by 4 variable version Modification of Diet in Renal Disease equation) or kidney function not stable (as defined by > 15% decrease in eGFR in 3 months before screening, unless due to medication change).
  • Blood Pressure: Uncontrolled hypertension defined as blood pressure (BP) greater than 150/90 millimeters of mercury (mm Hg) (treatment target greater than and equal to 140/80) as assessed by either : Blood pressures measured 3 times on each of at least 2 clinic visits during screening, after the patient has sat quietly for at least 5 minutes, with greater than 50% of measurements being greater than 150/90 or average daytime blood pressure on a 24 hour ambulatory blood pressure monitor.
  • Prior Therapy: Have received treatment with the following therapies at the times specified prior to Day 0: Therapy - B-cell targeted therapy except rituximab (e.g., other anti- CD20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], B lymphocyte stimulator-receptor fusion protein [BR3], transmembrane activator and calcium modulator and cyclophylin ligand interactor Fc, or belimumab), Time period: anytime; Therapy: Rituximab (Subjects with rituximab treatment between 1 and 2 years prior to Day 0 are eligible if there is documented evidence of B-cell repopulation to >50% of pre-treatment levels.), Period: 2 years; Therapy: Abatacept and any other biologic investigational agent other than B cell targeted therapy (i.e. not approved for sale in the country in which it is being used), Time Period: 364 days; Therapy: Cyclophosphamide or chlorambucil 3 or more courses of systemic corticosteroids for concomitant conditions (e.g., asthma, atopic dermatitis). (Topical or inhaled steroids are permitted.), Time Period: 180 days; Therapy: Anti-tumour necrosis factor (TNF) or anti-IL-6 therapy (e.g. adalimumab, etanercept, infliximab, tocilizumab). Interleukin-1 receptor antagonists (e.g. anakinra). Other immunosuppressive/immunomodulatory agents (e.g azathioprine, 6-mercaptopurine, mycophenolate mofetil (PO)/ mycophenolate mofetil hydrochloride (IV), mycophenolate sodium (PO), methotrexate, tacrolimus, sirolimus, thalidomide, leflunomide, mizoribine, ciclosporin). Intravenous immunoglobulin (IVIG). Plasmapheresis, leukapheresis, Time Period: 90 days; Therapy: A non-biologic investigational agent (i.e. not approved for sale in the country in which it is being used). Intravenous corticosteroid, Adrenocorticotropic hormone (ACTH). Adenocorticotropic hormone (ACTH), aliskiren A change in dose of >50% for angiotensin pathway antihypertensive (e.g., ACE inhibitor, angiotensin receptor blocker), Time Period: 60 days; Therapy: A live vaccine. Greater than 30 milligrams per day (mg/day) corticosteroid, Time Period: 30 days; Therapy: Greater than 10mg/day corticosteroid. A change in dose of a corticosteroid. Note: Changes to inhaled steroids and new topical immunosuppressive agents (e.g., eye drops, topical creams) are allowed, Time Period: 14 days;
  • Transplantation: Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
  • Cancer: Have a history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
  • Acute or chronic infection: Have required management of acute or chronic infections, as follows: Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria); Hospitalisation for treatment of infection within 60 days prior to Day 0; Use of parenteral (IV or intramuscular) antibiotics (anti-bacterials, anti-virals, anti-fungals, or anti-parasitic agents) within 60 days prior to Day 0.
  • Liver disease: Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Other diseases/conditions: Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to IMGN (i.e., cardiovascular, pulmonary, haematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases) which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.

or Have a planned surgical procedure or a history of any other medical disease (e.g. cardiopulmonary), laboratory abnormality, or condition (e.g. poor venous access) that, in the opinion of the investigator, makes the subject unsuitable for the study.

  • Positive serology: Have a historically positive human immunodeficiency virus (HIV) test or test positive at screening for HIV. Serologic evidence of Hepatitis B (HB) infection based on the results of testing for hepatitis B surface (antigen) (HBsAg), anti-HBc and anti-HBs as follows:- Patients positive for HBsAg are excluded: Patients negative for HBsAg and anti-HBc antibody but positive for anti-HBs antibody and with no history of Hepatitis B vaccination are excluded; Patients negative for HBsAg but positive for both anti-HBc and anti-HBs antibodies are excluded; Patients negative for HBsAg and anti-HBs antibody but positive for anti-HBc antibody are excluded. Positive test for Hepatitis C antibody confirmed on the same sample with a Hepatitis C Recombinant Immunoblot Assay (RIBA) immunoblot assay if available. Subjects who are positive for Hepatitis C antibody and who have a positive or indeterminate result when the Hepatitis C RIBA immunoblot assay is performed on the same sample, or where the Hepatitis C RIBA assay is not available, will not be eligible to participate.
  • Liver function tests: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) greater than and equal to 2x upper limit of normal (ULN); alkaline phosphatase and bilirubin greater than 1.5xULN (isolated bilirubin greater than 1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%).
  • Immunodeficiency: Have an IgA deficiency [immunoglobulin (Ig)A level \< 10 milligrams per deciliter (mg/dL)] or have IgG level \< 250 mg/dL and have previously received any non-glucocorticoid immunosuppression during the previous 6 months.
  • Laboratory test abnormalities: Have clinically significant abnormalities in screening laboratory assessments (not related to the disease), as judged by investigator.
  • Drug sensitivity / Anaphylaxis: History of sensitivity or intolerance to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. History of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.
  • Substance abuse: Evidence of current drug or alcohol abuse or dependence.
  • Blood donation: Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
14 participants (actual)

Study arms

  • Experimental
    Cohort 1

    10mg/kg belimumab intravenous (IV) administered at weeks 0 and 2, and then every 4 weeks, over a 24-week treatment period, resulting in a total of 8 doses, and will be assessed for the primary endpoint at week 28. Subjects will then enter the long term phase of the study and receive 10mg/kg belimumab every 4 weeks until week 100,or until they have been in complete remission for at least 3 months, resulting in up to 27 doses.

    Drug: belimumab

Interventions

  • Drugbelimumab

    10mg/kg administered intravenously

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Proteinuria Levels at Week 28

    Proteinuria based on urinary protein creatinine ratio (PCR) was measured from 2 consecutive 24 hour (h) urine collection pre and post dosing at Baseline and Week 28 and the mean PCR was determined at each time point. Baseline is defined as the mean of the pre and post dosing Day 0 values. The ratio is defined as the Week 28 value divided by the Baseline value. Ratio to Baseline: Estimated value = 0.76, 2-sided 95% confidence interval (CI)=0.57 to 1.01. The geometric mean method was used to calculate the CI. The analysis was performed on Intent-to-treat (ITT) Population which comprised of all eligible participants who received at least one dose of investigational drug. Only those participants available at the indicated time point (Week 28) were analyzed.

    Time frame: Baseline and Week 28

  2. Change From Baseline in Anti-phospholipase A2 Receptor (PLA2R) Autoantibody Titers at Week 28

    PLA2R autoantibody titers in serum were analyzed at Baseline and Week 28 by means of a validated anti- PLA2R enzyme linked immunosorbent assay (ELISA) from EuroImmun. Baseline is defined as the Day 0 value and change from Baseline was calculated as ratio to Baseline by dividing the Week 28 values with the Baseline values. Ratio to Baseline: Estimated value = 0.27, 2-sided 95% CI=0.12 to 0.58. The geometric mean method was used to calculate the CI.

    Time frame: Baseline and Week 28

Secondary outcomes

  1. Proteinuria Levels at the Indicated Time Points

    Proteinuria based on urinary protein creatinine ratio (PCR) measured from 2 consecutive 24h urine collections at Baseline and Week 28, from a pre-intervention spot urine sample and 24 hour urine collection after visit at Weeks 12, 52, 76 and 104, and from a spot urine sample at week 128. Mean PCR was calculated at each time point where there were 2 samples. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Week 12, 28, 52, 76, 104 and 128/6 month follow-up

  2. Change From Baseline in Proteinuria Levels at the Indicated Time Points

    Proteinuria based on urinary protein creatinine ratio (PCR) measured from 2 consecutive 24h urine collections at Baseline and Week 28, from a pre-intervention spot urine sample and 24 hour urine collection after visit at Weeks 12, 52, 76 and 104, and from a spot urine sample at week 128. Mean PCR was calculated at each time point where there were 2 samples. Baseline is defined as Day 0 value and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Week 12, 28, 52, 76, 104 and Week 128/6 month follow up

  3. Anti-phospholipase A2 Receptor (PLA2R) Autoantibody Levels at Indicated Time Points

    Anti-PLA2R autoantibody titers in serum were analyzed by means of a validated anti-PLA2R enzyme linked immunosorbent assay (ELISA) assay from Euroimmun. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Week 12, 28, 52, 76, 104 and 128/6 month follow-up

  4. Change From Baseline in Anti-PLA2R Autoantibody Titers at the Indicated Time Points

    Anti-PLA2R autoantibody titers in serum were analyzed by means of a validated anti- PLA2R enzyme linked immunosorbent assay (ELISA) from Euroimmun. Baseline is defined as the Day 0 value and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128.

  5. Number of Participants With Complete or Partial Remission

    Complete remission is defined as PCR \<30 mg/mmol (proteinuria \<0.3grams \[g\]/24 h) with no worsening in renal function (estimated glomerular filtration rate \[eGFR\] reduction from Baseline \<15 percent). Partial remission is defined as PCR \<350 mg/mmol (proteinuria \<3.5 g/24 h) but \>= 30 mg/mmol (proteinuria \>= 0.3g/24h) and decrease of \>50 percent from Day 0 Baseline, together with no consistent worsening in renal function (eGFR reduction from Baseline \<15percent). Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128

  6. Time to Complete or Partial Remission

    Time to complete or partial remission was estimated using the Kaplan-Meier method. Complete remission is defined as PCR \<30 mg/mmol (proteinuria \<0.3g/24 h) with no worsening in renal function (eGFR reduction from Baseline \<15 percent ). Partial remission is defined as PCR \<350 mg/mmol (proteinuria \<3.5 g/24 h) but \>= 30 mg/mmol (proteinuria \>= 0.3g/24h) and decrease of \>50 percent from Day 0 Baseline, together with no consistent worsening in renal function (eGFR reduction from Baseline \<15 percent). Only 1 participant reached complete remission. Hence, statistical analysis for complete remission was not performed.

    Time frame: Baseline and up to Week 128/6 month follow up

  7. Duration of Complete or Partial Remission

    Complete remission is defined as PCR \<30 mg/mmol (proteinuria \<0.3g/24 h) with no worsening in renal function (eGFR reduction from Baseline \<15percent). Partial remission is defined as PCR \<350 mg/mmol (proteinuria \<3.5 g/24 h) but \>= 30 mg/mmol (proteinuria \>= 0.3g/24h) and decrease of \>50% from Day 0 Baseline, together with no consistent worsening in renal function (eGFR reduction from Baseline \<15percent). Only those participants available at the specified time points were analyzed (represented by n=X in category titles). NA indicates that data was not available as only 1 participant reached complete remission. Hence, standard deviation for complete remission was not calculated.

    Time frame: Baseline and up to Week 128/6 month follow up

  8. Number of Participants With PLA2R Autoantibody Remission

    Incidence of anti-PLA2R autoantibody remission were evaluated by full response and partial response. Full response is defined as antibody undetectable, partial response is defined as reduction in titers by 50 percent. For anti PLA2R autoantibody data, log transformation was applied before the formal analyses. Anti-PLA2R autoantibody blood samples were evaluated at Week 12, 28, 52, 76, 104 and 128/6 week post last-dose. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128

  9. Time to Anti-PLA2R Autoantibody Remission

    Time to anti-PLA2R autoantibody remission was estimated using Kaplan-Meier method for full response and partial response full response with antibody undetectable and partial response with reduction in titers by 50 percent.

    Time frame: Baseline and up to Week 128/6 month follow up

  10. Number of Participants With Anti-PLA2R Autoantibody Relapse

    Incidence of anti-PLA2R autoantibody relapse defined as antibody detectable after previously undetectable. Anti-PLA2R autoantibody blood samples were evaluated at Week 12, 28, 52, 76, 104/4 week post last dose, Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

    Time frame: Baseline and up to Week 128/6 month follow up

  11. eGFR Levels at the Indicated Time Points

    eGFR was assessed from levels of creatinine using the 4 variable version of the modification of diet in renal disease (MDRD) equation as recommended by National Kidney Foundation-Chronic Kidney Disease (NKF-CKD) guidelines. Baseline for eGFR is defined as the mean of the screening and Day 0 values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up.

  12. Change From Baseline in eGFR Levels at the Indicated Time Points

    eGFR was assessed from levels of creatinine using the 4 variable version of the modification of diet in renal disease (MDRD) equation as recommended by national kidney foundation-chronic kidney disease (NKF-CKD) guidelines. Baseline for eGFR is defined as the mean of the Screening and Day 0 values and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and up to Week 128/6 month follow up

  13. Serum Creatinine Levels at the Indicated Time Points

    Serum creatinine was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum creatinine is defined as the mean of the Screening and Day 0 values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up

  14. Change From Baseline in Serum Creatinine Levels at the Indicated Time Points

    Serum creatinine was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum creatinine is defined as the mean of the Screening and Day 0 values and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up

  15. Serum Albumin Levels at Indicated Time Points

    Serum albumin was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum albumin is defined as the mean of the Screening and Day 0 values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up.

  16. Change From Baseline in Levels of Serum Albumin at the Indicated Time Points

    Serum albumin was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum albumin is defined as the mean of the Screening and Day 0 values and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up

  17. Serum Cholesterol Levels at Indicated Time Points

    Serum cholesterol was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum cholesterol is defined as the mean of the Screening and Day 0 values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up

  18. Change From Baseline in Serum Cholesterol at the Indicated Time Points

    Serum cholesterol was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum cholesterol is defined as the mean of the Screening and Day 0 values and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up

  19. Serum Immunoglobulin G (IgG) Levels at Indicated Time Points

    Serum IgG was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum IgG is defined as the pre-dose Day 0 value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up

  20. Change From Baseline in Serum IgG at the Indicated Time Points

    Serum IgG was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum IgG is defined as the pre-dose Day 0 value and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow up

  21. Number of Participants With Edema and Edema Extending Beyond Calf

    Reduction of proteinuria lessens the risk of thromboembolic and cardiovascular effects and reduces the edema in participants. Investigators physically reviewed participants for clinical manifestations of idiopathic membranous glomerulonephropathy (IMGN) (e.g. edema extending beyond calf) during study and analysis was performed at Week 12, 28, 52, 76 Week 104. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

    Time frame: Baseline and Weeks 12, 28, 52, 76, and 104

  22. Summary of Maximum Observed Serum Concentration (Cmax) of Belimumab at the Indicated Time Points

    The first occurrence of Cmax was determined directly from the serum concentration-time data. The pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis and all calculations of non-compartmental parameters are being based on actual sampling times.

    Time frame: Baseline and up to 4 week post last dose

  23. Summary of Minimum Observed Concentration (Cmin) of Belimumab at the Indicated Time Points

    Trough concentration (Cmin) samples collected on the specified days are being used to assess attainment whether there was sufficient belimumab despite it being lost in the urine from the proteinuria and to check if it improved as proteinuria resolved. Analysis was performed on pre-infusion samples at weeks 2,4,8,12,28,40,52,76 and the 4 week post last-dose.

    Time frame: Baseline and up to 4 week post last dose

  24. Summary of Area Under the Serum Concentration-time Curve to the Last Quantifiable Concentration (AUC[0-2])

    The AUC(0-2) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples for PK analysis were collected at the following time points: pre-dose (on dosing days): Days 0, 1, 4, 7, 14 and Week 4, 8, 12, 28, 40, 52, 76 and 4 week post last dose. Post-dose (5 minutes after dosing complete): Days 0 and 28. The results will be posted at later date following post hoc analysis.

    Time frame: Baseline and up to 4 week post last dose

  25. Summary of Total Amount of Urine Excreted Ae(0-24)

    PK parameters from the urine concentration data: urine Ae(0-24) were assessed. 24 h urine collections for PK analysis were collected after the Day 0 and Weeks 12, 28, 52, 76 doses and at the 4 week post last dose visit. A population approach was undertaken to characterize the population PK parameters and associated variability of belimumab in nephrotic participants. The population approach could have provided derived clearance of belimumab for each participant after the first dose. The population PK analysis was conducted using nonlinear mixed-effect modeling (NONMEM) or appropriate nonlinear mixed-effect analysis software. Several samples were taken pre-dose at Day 0 and some at week 12 incorrectly which affects interpretation.

    Time frame: Baseline and Up to 4 week post last dose

  26. Change From Baseline in Short Form (SF)-36 v2 Quality of Life (QoL) Questionnaire Score

    Health-related quality of life was assessed through participant self-completion of the short form health survey (SF-36 version \[v2\]), a general health related quality of life metrics. Norm-based Scores (NBS) for physical functioning, role emotional, role physical were assessed. The remaining SF-36 component scores require re-scaling and therefore will be added at a later date. SF-36 was administered prior to any procedures at Weeks 12, 28, 52, 76 and 104/4 week post last dose. Item score were recorded and higher score represented better health status. Baseline is defined as Day 0 pre dose value and change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

    Time frame: Baseline and up to Week 104/4 week post last dose

  27. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The analysis was performed on Safety Population which comprised of all participants who were randomized into the study. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, Requires hospitalization or prolongation of existing hospitalization, Results in disability/incapacity, is a congenital anomaly/birth defect, may require medical or surgical intervention, is associated with liver injury and impaired liver function.

    Time frame: Baseline and up to Week 128/6 month follow up

  28. Number of Participants With Abnormal Clinical Chemistry and Hematology Values

    Blood samples were collected from participants for evaluation of clinical chemistry and hematology parameters. The clinical chemistry parameters included albumin, alkaline phosphatase (alk.phosph.), alanine amino transferase (ALT), aspartate amino transferase (AST), total and direct bilirubin, calcium, cholesterol, chloride, carbon dioxide, creatinine, gamma glutamyl transferase (GGT), glucose, potassium, lactate dehydrogenase (LD), magnesium, sodium, phosphorus, total protein, blood urea nitrogen (BUN) and uric acid. The hematology parameters included basophils, eosinophil, hemoglobin, hematocrit, lymphocytes, monocytes, total neutrophils, platelets, red blood cells (RBC) count and white blood cells (WBC) count. Participants were counted in the category that their value changes to (low or high) for the specific time points. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and up to Week 116/16 week follow-up visit

  29. Number of Participants With Urinalysis Dipstick Findings

    Urine samples were collected for urinalysis by dipstick method from Baseline up to Week 116/16 months follow up and number of participants with findings were presented for Baseline, Week 12, 28, 52, 76, 104/4 weeks post last-dose and Week 116/16 week follow up (WF). The urinalysis parameters included occult blood, glucose, ketones, protein. The findings were presented as trace or 1/10 g/100 milliliter (dL), trace, negative, 4+, 3+, 3+ or 1 g/dL, 2+ or 1/2 g/dL, 2+, 1+ or 1/4 g/dL and 1+. Only participants present at the specific time points were presented (represented by n=X in the category titles).

    Time frame: Baseline and up to Week 116/16 Week follow up

  30. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    SBP and DBP were measured from Baseline throughout the treatment period up to Week 116/ 16 week follow-up visit. The Baseline value was taken at Day 0 pre dose and change from Baseline was defined as post dose visit value minus Baseline value. Mean and standard deviation (SD) were measured and presented for Week 12, 28, 52, 76, 104 withdrawn visit, 4 Week post last dose and 16 Week follow-up visit. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Time frame: Baseline and up to week 116/16 week follow-up visit

  31. Change From Baseline in Pulse Rate

    Pulse rate was measured from Baseline throughout the treatment period up to Week 116/ 16 week follow-up visit. The Baseline value was taken at Day 0 pre dose and change from Baseline was defined as post dose visit value minus Baseline value. Mean and standard deviation (SD) were measured and presented for Week 12, 28, 52, 76, 104 withdrawn visit, 4 Week post last dose and 16 Week post last dose visits. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Time frame: Baseline and up to Week 116/16 week follow-up visit

  32. Change From Baseline in Temperature

    Temperature was measured from Baseline throughout the treatment period up to Week 116/ 16 week follow-up visit. The Baseline value was taken at Day 0 pre dose and change from Baseline was defined as post dose visit value minus Baseline value. Mean and standard deviation (SD) were measured and presented for Week 12, 28, 52, 76, 104 withdrawn visit, 4 Week post last dose and 16 week post last dose visits. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Time frame: Baseline and up to Week 116/16 week follow-up visit

  33. Number of Participants With Positive Immunogenicity Findings

    Blood samples of participants were collected pre-dose on Weeks 0, 12, 28, 40, 52, 76, 4 week post last dose and 16 week post last dose visit for belimumab immunogenicity assay. No participants showed positive immunogenicity findings.

    Time frame: Baseline and up to Week 116/16 week follow-up visit

  34. Urine Membrane Attack Complex (MAC) Levels

    Urine membrane attack complex was assayed quantitatively by ELISA method. Urine MAC samples were collected at Day 0 and Weeks 8, 28, 52, 76 and 4 week post last dose. Results were normalized using urine creatinine concentration to adjust for urine dilution. Endpoint was moved to 'Exploratory' in Protocol amendment 5 as risk of availability of functioning assay for urine membrane attack complex was noted. No assay was subsequently found and samples were not analyzed

    Time frame: Baseline and up to 4 week post last dose

  35. Change From Baseline in Urine Membrane Attack Complex (MAC)

    Urine membrane attack complex will be assayed quantitatively by ELISA method. Urine MAC samples are being collected at Day 0 and Weeks 8, 28, 52, 76 and 4 week post last dose. Results will be normalized using urine creatinine concentration to adjust for urine dilution, before calculation of the ratio as value at time point divided by value at Baseline (Day 0). Endpoint was changed to 'exploratory' as risk of availability of functioning assay for urine membrane attack complex was noted. No assay was subsequently found and samples were not analyzed.

    Time frame: Baseline and up to 4 week post last dose

  36. Change From Baseline in B Cell and T Cell Markers Concentration

    B cell Facs panels were used to measure changes over the course of therapy in B cell subsets such as transitional, naïve, memory and plasma B cell compartments by percent of the B cell compartments and absolute numbers. T cell Facs panel were used to measure changes in T cell subsets, such as T regs and CD4+ and CD8+ T cells, in terms of numbers and expression of activation markers to establish if B cell targeting with belimumab affects the T cell compartment perhaps through limiting B cell antigen presentation or cytokine release. Baseline is defined as Day 0 value and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Time frame: Baseline and up to Week 128/6 month post last dose

  37. Change From Baseline in Cytokines/Chemokine

    Cytokine/chemokine associated with T helper skewing or autoimmune pathology will be analyzed using Luminex, ELISA. Serum analyte quantification were used to confirm altered protein levels of any gene expression increases or decreases identified by transcriptomic analysis. Endpoint was moved to 'Exploratory' in Protocol amendment 5 as benefits of assessing cytokines was deemed low. Samples were not analyzed.

    Time frame: Baseline and up to Week 104/4 week post last dose

  38. Serum BLys Levels

    Free BLyS protein were analyzed using an ELISA. Serum samples were collected before treatment and after belimumab washout at Week 0 and Week 116/16 week follow-up visit.

    Time frame: Baseline and Week 116/16 week follow-up visit

  39. Urine BLys Levels as a Ratio to Creatinine

    B lymphocyte stimulator (BLyS) normalized by creatinine as a ratio of BLyS: creatinine. Free BLyS protein is being analyzed using an ELISA. Urine samples are being collected before treatment and after belimumab washout at Week 0 and Week 116/16 week follow-up visit. Only raw BLyS values available and unable to be assessed due to lack of comparison to a creatinine as a urine concentration marker.

    Time frame: Baseline and Week 116/16 week follow-up visit

07

Results

Posted Jun 1, 2015

Participant flow

Eligible participants were recruited from July 2012 until March 2014, into this 2 part study of a initial treatment phase, a long term treatment phase, and then followed up for a further 6 months. Results have previously been presented for the initial treatment phase, up to the Week 28 and are now presented for the completed study.

Participant flow — Overall Study
MilestoneBelimumab 10 mg/kg IV
Started14
Completed8
Not completed6
Withdrew: Adverse event1
Withdrew: Lack of efficacy3
Withdrew: Other: reached stopping criteria1
Withdrew: Other:treatment stopped due to remission1

Outcome measures

PrimaryChange From Baseline in Proteinuria Levels at Week 28

Proteinuria based on urinary protein creatinine ratio (PCR) was measured from 2 consecutive 24 hour (h) urine collection pre and post dosing at Baseline and Week 28 and the mean PCR was determined at each time point. Baseline is defined as the mean of the pre and post dosing Day 0 values. The ratio is defined as the Week 28 value divided by the Baseline value. Ratio to Baseline: Estimated value = 0.76, 2-sided 95% confidence interval (CI)=0.57 to 1.01. The geometric mean method was used to calculate the CI. The analysis was performed on Intent-to-treat (ITT) Population which comprised of all eligible participants who received at least one dose of investigational drug. Only those participants available at the indicated time point (Week 28) were analyzed.

Time frame:
Baseline and Week 28
Reported as:
Geometric mean · Ratio
Change From Baseline in Proteinuria Levels at Week 28
RatioBelimumab 10 mg/kg IV
Change From Baseline in Proteinuria Levels at Week 280.7552 ± 45.0
Statistical analysis
  • Belimumab 10 mg/kg IV · Geometric mean: 0.76 · 95% CI 0.57 to 1.01
PrimaryChange From Baseline in Anti-phospholipase A2 Receptor (PLA2R) Autoantibody Titers at Week 28

PLA2R autoantibody titers in serum were analyzed at Baseline and Week 28 by means of a validated anti- PLA2R enzyme linked immunosorbent assay (ELISA) from EuroImmun. Baseline is defined as the Day 0 value and change from Baseline was calculated as ratio to Baseline by dividing the Week 28 values with the Baseline values. Ratio to Baseline: Estimated value = 0.27, 2-sided 95% CI=0.12 to 0.58. The geometric mean method was used to calculate the CI.

Time frame:
Baseline and Week 28
Reported as:
Geometric mean · Ratio
Change From Baseline in Anti-phospholipase A2 Receptor (PLA2R) Autoantibody Titers at Week 28
RatioBelimumab 10 mg/kg IV
Change From Baseline in Anti-phospholipase A2 Receptor (PLA2R) Autoantibody Titers at Week 280.2666 ± 171.0
Statistical analysis
  • Belimumab 10 mg/kg IV · Geometric mean: 0.27 · 95% CI 0.12 to 0.58
SecondaryProteinuria Levels at the Indicated Time Points

Proteinuria based on urinary protein creatinine ratio (PCR) measured from 2 consecutive 24h urine collections at Baseline and Week 28, from a pre-intervention spot urine sample and 24 hour urine collection after visit at Weeks 12, 52, 76 and 104, and from a spot urine sample at week 128. Mean PCR was calculated at each time point where there were 2 samples. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Week 12, 28, 52, 76, 104 and 128/6 month follow-up
Reported as:
Geometric mean · milligrams per millimole (mg/mmol)
Proteinuria Levels at the Indicated Time Points
milligrams per millimole (mg/mmol)Belimumab 10 mg/kg IV
Baseline, n=14724.3157 ± 40.2
Week 12, n=13670.8655 ± 46.9
Week 28, n=11498.1255 ± 40.9
Week 52, n=9356.4209 ± 174.8
Week 76, n=8274.9714 ± 70.4
Week 104, n=10129.9761 ± 186.0
Week 128, n=975.2359 ± 136.4
SecondaryChange From Baseline in Proteinuria Levels at the Indicated Time Points

Proteinuria based on urinary protein creatinine ratio (PCR) measured from 2 consecutive 24h urine collections at Baseline and Week 28, from a pre-intervention spot urine sample and 24 hour urine collection after visit at Weeks 12, 52, 76 and 104, and from a spot urine sample at week 128. Mean PCR was calculated at each time point where there were 2 samples. Baseline is defined as Day 0 value and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Week 12, 28, 52, 76, 104 and Week 128/6 month follow up
Reported as:
Geometric mean · Ratio
Change From Baseline in Proteinuria Levels at the Indicated Time Points
RatioBelimumab 10 mg/kg IV
Week 12; n= 130.9437 ± 39.3
Week 28; n= 110.7552 ± 45.0
Week 52; n= 90.5297 ± 206.7
Week 76; n= 80.4177 ± 54.3
Week 104; n= 100.1874 ± 189.3
Week 128; n= 90.1118 ± 139.1
SecondaryAnti-phospholipase A2 Receptor (PLA2R) Autoantibody Levels at Indicated Time Points

Anti-PLA2R autoantibody titers in serum were analyzed by means of a validated anti-PLA2R enzyme linked immunosorbent assay (ELISA) assay from Euroimmun. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Week 12, 28, 52, 76, 104 and 128/6 month follow-up
Reported as:
Geometric mean · relative units per milliliter (RU/mL)
Anti-phospholipase A2 Receptor (PLA2R) Autoantibody Levels at Indicated Time Points
relative units per milliliter (RU/mL)Belimumab 10 mg/kg IV
Baseline, n=14168.3 ± 138.9
Week 12, n=1391.0 ± 200.4
Week 28, n=1146.4 ± 319.6
Week 52, n=912.9 ± 358.4
Week 76, n=87.5 ± 140.4
Week 104, n=103.7 ± 72.7
Week 128, n=84.4 ± 112.0
SecondaryChange From Baseline in Anti-PLA2R Autoantibody Titers at the Indicated Time Points

Anti-PLA2R autoantibody titers in serum were analyzed by means of a validated anti- PLA2R enzyme linked immunosorbent assay (ELISA) from Euroimmun. Baseline is defined as the Day 0 value and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128.
Reported as:
Geometric mean · Ratio
Change From Baseline in Anti-PLA2R Autoantibody Titers at the Indicated Time Points
RatioBelimumab 10 mg/kg IV
Week 12; n= 130.5362 ± 58.1
Week 28; n= 110.2666 ± 171.0
Week 52; n= 90.0737 ± 130.3
Week 76; n= 80.0436 ± 102.8
Week 104; n= 100.0212 ± 169.1
Week 128; n= 80.0284 ± 243.7
SecondaryNumber of Participants With Complete or Partial Remission

Complete remission is defined as PCR \<30 mg/mmol (proteinuria \<0.3grams \[g\]/24 h) with no worsening in renal function (estimated glomerular filtration rate \[eGFR\] reduction from Baseline \<15 percent). Partial remission is defined as PCR \<350 mg/mmol (proteinuria \<3.5 g/24 h) but \>= 30 mg/mmol (proteinuria \>= 0.3g/24h) and decrease of \>50 percent from Day 0 Baseline, together with no consistent worsening in renal function (eGFR reduction from Baseline \<15percent). Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128
Reported as:
Number · Participants
Number of Participants With Complete or Partial Remission
ParticipantsBelimumab 10 mg/kg IV
Week 12; Partial remission; n= 130
Week 12; Complete remission; n= 130
Week 28; Partial remission; n= 111
Week 28; Complete remission; n= 110
Week 52; Partial remission; n= 92
Week 52; Complete remission; n= 91
Week 76; Partial remission; n= 83
Week 76; Complete remission; n= 80
Week 104; Partial remission; n= 106
Week 104; Complete remission; n= 101
Week 128; Partial remission; n= 96
Week 128; Complete remission; n= 91
SecondaryTime to Complete or Partial Remission

Time to complete or partial remission was estimated using the Kaplan-Meier method. Complete remission is defined as PCR \<30 mg/mmol (proteinuria \<0.3g/24 h) with no worsening in renal function (eGFR reduction from Baseline \<15 percent ). Partial remission is defined as PCR \<350 mg/mmol (proteinuria \<3.5 g/24 h) but \>= 30 mg/mmol (proteinuria \>= 0.3g/24h) and decrease of \>50 percent from Day 0 Baseline, together with no consistent worsening in renal function (eGFR reduction from Baseline \<15 percent). Only 1 participant reached complete remission. Hence, statistical analysis for complete remission was not performed.

Time frame:
Baseline and up to Week 128/6 month follow up
Reported as:
Median · Weeks
Time to Complete or Partial Remission
WeeksBelimumab 10 mg/kg IV
Time to Complete or Partial Remission68.20 (28.00 to 93.60)
SecondaryDuration of Complete or Partial Remission

Complete remission is defined as PCR \<30 mg/mmol (proteinuria \<0.3g/24 h) with no worsening in renal function (eGFR reduction from Baseline \<15percent). Partial remission is defined as PCR \<350 mg/mmol (proteinuria \<3.5 g/24 h) but \>= 30 mg/mmol (proteinuria \>= 0.3g/24h) and decrease of \>50% from Day 0 Baseline, together with no consistent worsening in renal function (eGFR reduction from Baseline \<15percent). Only those participants available at the specified time points were analyzed (represented by n=X in category titles). NA indicates that data was not available as only 1 participant reached complete remission. Hence, standard deviation for complete remission was not calculated.

Time frame:
Baseline and up to Week 128/6 month follow up
Reported as:
Mean · Days
Duration of Complete or Partial Remission
DaysBelimumab 10 mg/kg IV
Complete remission; n= 1365.0 ± NA
Partial remission; n= 9378.6 ± 186.15
SecondaryNumber of Participants With PLA2R Autoantibody Remission

Incidence of anti-PLA2R autoantibody remission were evaluated by full response and partial response. Full response is defined as antibody undetectable, partial response is defined as reduction in titers by 50 percent. For anti PLA2R autoantibody data, log transformation was applied before the formal analyses. Anti-PLA2R autoantibody blood samples were evaluated at Week 12, 28, 52, 76, 104 and 128/6 week post last-dose. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128
Reported as:
Number · Participants
Number of Participants With PLA2R Autoantibody Remission
ParticipantsBelimumab 10 mg/kg IV
Week 12; full response; n= 131
Week 12; partial response; n= 133
Week 28; full response; n= 113
Week 28; partial response; n= 116
Week 52; full response; n= 94
Week 52; partial response; n= 95
Week 76; full response; n= 84
Week 76; partial response; n= 84
Week 104; full response; n= 1010
Week 104; partial response; n= 100
Week 128; Full response; n= 88
Week 128; partial response; n= 80
SecondaryTime to Anti-PLA2R Autoantibody Remission

Time to anti-PLA2R autoantibody remission was estimated using Kaplan-Meier method for full response and partial response full response with antibody undetectable and partial response with reduction in titers by 50 percent.

Time frame:
Baseline and up to Week 128/6 month follow up
Reported as:
Median · Weeks
Time to Anti-PLA2R Autoantibody Remission
WeeksBelimumab 10 mg/kg IV
Partial response16.20 (8.00 to 24.00)
Complete response82.00 (16.00 to 92.00)
SecondaryNumber of Participants With Anti-PLA2R Autoantibody Relapse

Incidence of anti-PLA2R autoantibody relapse defined as antibody detectable after previously undetectable. Anti-PLA2R autoantibody blood samples were evaluated at Week 12, 28, 52, 76, 104/4 week post last dose, Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Time frame:
Baseline and up to Week 128/6 month follow up
Reported as:
Number · Participants
Number of Participants With Anti-PLA2R Autoantibody Relapse
ParticipantsBelimumab 10 mg/kg IV
Week 12; n= 130
Week 28; n= 110
Week 52; n= 90
Week 76; n= 80
Week 104; n= 100
Week 128; n= 80
SecondaryeGFR Levels at the Indicated Time Points

eGFR was assessed from levels of creatinine using the 4 variable version of the modification of diet in renal disease (MDRD) equation as recommended by National Kidney Foundation-Chronic Kidney Disease (NKF-CKD) guidelines. Baseline for eGFR is defined as the mean of the screening and Day 0 values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up.
Reported as:
Geometric mean · milliliter/minute (mL/min/1.73meter^2)
eGFR Levels at the Indicated Time Points
milliliter/minute (mL/min/1.73meter^2)Belimumab 10 mg/kg IV
Baseline; n= 1469.8170 ± 32.9
Week 12; n= 1366.2639 ± 35.4
Week 28; n= 1165.0866 ± 36.1
Week 52; n= 765.1308 ± 45.0
Week 76; n= 861.6732 ± 47.1
Week 104; n= 1069.7692 ± 39.1
Week 128; n= 964.7984 ± 39.2
SecondaryChange From Baseline in eGFR Levels at the Indicated Time Points

eGFR was assessed from levels of creatinine using the 4 variable version of the modification of diet in renal disease (MDRD) equation as recommended by national kidney foundation-chronic kidney disease (NKF-CKD) guidelines. Baseline for eGFR is defined as the mean of the Screening and Day 0 values and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and up to Week 128/6 month follow up
Reported as:
Geometric mean · Ratio
Change From Baseline in eGFR Levels at the Indicated Time Points
RatioBelimumab 10 mg/kg IV
Week 2, n=140.9954 ± 10.8
Week 4, n= 130.9190 ± 16.4
Week 8, n= 130.9035 ± 16.2
Week 12, n= 130.9339 ± 17.1
Week 16, n= 120.9521 ± 12.5
Week 20, n= 80.9819 ± 11.8
Week 24, n= 110.9274 ± 17.1
Week 28, n= 110.9694 ± 21.1
Week 32, n= 91.0099 ± 19.5
Week 36, n= 110.9692 ± 17.4
Week 40, n= 110.9425 ± 20.8
Week 44, n= 100.9531 ± 22.6
Week 48, n= 80.9929 ± 23.8
Week 52, n= 70.9290 ± 27.7
Week 56, n= 91.0181 ± 21.9
Week 60, n= 90.9805 ± 26.8
Week 64, n=91.0217 ± 23.5
Week 68, n=81.0233 ± 24.6
Week 72, n=81.0168 ± 28.3
Week 76, n=81.0055 ± 33.3
Week 80, n=81.0431 ± 21.6
Week 84, n=80.9959 ± 25.3
Week 88, n=81.0529 ± 16.3
Week 92, n=81.0052 ± 26.3
Week 96, n=81.1204 ± 22.1
Week 100, n=81.1122 ± 24.7
Week 104, n=101.0480 ± 23.3
Week 116; n= 81.0373 ± 19.8
Week 128, n=90.9971 ± 35.2
SecondarySerum Creatinine Levels at the Indicated Time Points

Serum creatinine was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum creatinine is defined as the mean of the Screening and Day 0 values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up
Reported as:
Geometric mean · micromoles/liter (µmol/L)
Serum Creatinine Levels at the Indicated Time Points
micromoles/liter (µmol/L)Belimumab 10 mg/kg IV
Baseline; n= 1497.1658 ± 22.8
Week 12; n= 13100.6421 ± 26.8
Week 28; n= 1199.9535 ± 24.8
Week 52; n= 796.6583 ± 30.2
Week 76; n= 8103.0265 ± 32.8
Week 104; n= 1092.4547 ± 29.6
Week 128; n= 997.7260 ± 29.7
SecondaryChange From Baseline in Serum Creatinine Levels at the Indicated Time Points

Serum creatinine was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum creatinine is defined as the mean of the Screening and Day 0 values and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up
Reported as:
Geometric mean · Ratio
Change From Baseline in Serum Creatinine Levels at the Indicated Time Points
RatioBelimumab 10 mg/kg IV
Week 12; n= 131.0530 ± 14.8
Week 28; n= 111.0202 ± 18.6
Week 52; n= 71.0581 ± 23.7
Week 76; n= 80.9818 ± 28.7
Week 104; n= 100.9467 ± 20.1
Week 128; n= 90.9874 ± 30.4
SecondarySerum Albumin Levels at Indicated Time Points

Serum albumin was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum albumin is defined as the mean of the Screening and Day 0 values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up.
Reported as:
Geometric mean · grams per liter (g/L)
Serum Albumin Levels at Indicated Time Points
grams per liter (g/L)Belimumab 10 mg/kg IV
Baseline; n= 1423.3306 ± 22.7
Week 12; n= 1324.4204 ± 27.5
Week 28; n= 1127.8397 ± 23.4
Week 52; n= 731.9927 ± 18.3
Week 76; n= 833.9484 ± 10.9
Week 104; n= 1039.1015 ± 7.5
Week 128; n= 939.2009 ± 8.8
SecondaryChange From Baseline in Levels of Serum Albumin at the Indicated Time Points

Serum albumin was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum albumin is defined as the mean of the Screening and Day 0 values and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up
Reported as:
Geometric mean · ratio
Change From Baseline in Levels of Serum Albumin at the Indicated Time Points
ratioBelimumab 10 mg/kg IV
Week 12; n= 131.0324 ± 15.0
Week 28; n= 111.1211 ± 16.9
Week 52; n= 71.2828 ± 28.1
Week 76; n= 81.3695 ± 23.8
Week 104; n= 101.5879 ± 19.6
Week 128; n= 91.5799 ± 24.7
SecondarySerum Cholesterol Levels at Indicated Time Points

Serum cholesterol was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum cholesterol is defined as the mean of the Screening and Day 0 values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up
Reported as:
Geometric mean · millimoles per liter (mmol/L)
Serum Cholesterol Levels at Indicated Time Points
millimoles per liter (mmol/L)Belimumab 10 mg/kg IV
Baseline; n= 147.6423 ± 36.0
Week 12; n= 137.2336 ± 31.5
Week 28; n= 116.2740 ± 23.1
Week 52; n= 75.8724 ± 18.6
Week 76; n= 85.0211 ± 18.4
Week 104; n= 104.8001 ± 24.5
Week 128; n= 94.2407 ± 12.7
SecondaryChange From Baseline in Serum Cholesterol at the Indicated Time Points

Serum cholesterol was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum cholesterol is defined as the mean of the Screening and Day 0 values and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up
Reported as:
Geometric mean · mmol/L
Change From Baseline in Serum Cholesterol at the Indicated Time Points
mmol/LBelimumab 10 mg/kg IV
Week 12; n= 130.9238 ± 16.8
Week 28; n= 110.8896 ± 14.3
Week 52; n= 70.8571 ± 16.7
Week 76; n= 80.7111 ± 15.0
Week 104; n= 100.6851 ± 17.3
Week 128; n= 90.6140 ± 15.7
SecondarySerum Immunoglobulin G (IgG) Levels at Indicated Time Points

Serum IgG was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum IgG is defined as the pre-dose Day 0 value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow-up
Reported as:
Mean · g/L
Serum Immunoglobulin G (IgG) Levels at Indicated Time Points
g/LBelimumab 10 mg/kg IV
Baseline; n= 144.026 ± 1.6810
Week 12; n= 133.871 ± 1.5266
Week 28; n= 114.405 ± 1.7833
Week 52; n= 85.823 ± 2.2572
Week 76; n= 86.050 ± 2.1103
Week 104; n= 107.611 ± 2.8301
Week 128; n= 98.609 ± 2.2597
SecondaryChange From Baseline in Serum IgG at the Indicated Time Points

Serum IgG was assessed as a clinical chemistry laboratory parameter from Baseline up to Week 128/6 month follow-up visit. Baseline for serum IgG is defined as the pre-dose Day 0 value and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, 104 and 128/6 month follow up
Reported as:
Mean · Ratio
Change From Baseline in Serum IgG at the Indicated Time Points
RatioBelimumab 10 mg/kg IV
Week 12; n= 130.055 ± 0.6625
Week 28; n= 110.469 ± 1.4287
Week 52; n= 81.525 ± 2.4411
Week 76; n= 81.619 ± 1.6681
Week 104; n= 103.613 ± 2.5488
Week 128; n= 94.334 ± 2.0289
SecondaryNumber of Participants With Edema and Edema Extending Beyond Calf

Reduction of proteinuria lessens the risk of thromboembolic and cardiovascular effects and reduces the edema in participants. Investigators physically reviewed participants for clinical manifestations of idiopathic membranous glomerulonephropathy (IMGN) (e.g. edema extending beyond calf) during study and analysis was performed at Week 12, 28, 52, 76 Week 104. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Time frame:
Baseline and Weeks 12, 28, 52, 76, and 104
Reported as:
Number · Participants
Number of Participants With Edema and Edema Extending Beyond Calf
ParticipantsBelimumab 10 mg/kg IV
Week 0; oedema; n= 1413
Week 0; oedema extending beyond calf; n= 145
Week 12; oedema; n= 129
Week 12; Oedema extending beyond calf; n= 121
Week 28;Oedema; n= 117
Week 28; Oedema extending beyond calf; n= 111
Week 52; oedema; n= 94
Week 52;Oedema extending beyond calf; n= 91
Week 76;Oedema; n=84
Week 76;Oedema extending beyond calf; n= 80
4 Week post final dose (PFD); Oedema; n=106
4 Week PFD; Oedema extending beyond calf; n= 101
Week 104 withdrawn (WD); Oedema; n= 10
Week 104 WD;Oedema extending beyond calf; n= 10
SecondarySummary of Maximum Observed Serum Concentration (Cmax) of Belimumab at the Indicated Time Points

The first occurrence of Cmax was determined directly from the serum concentration-time data. The pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis and all calculations of non-compartmental parameters are being based on actual sampling times.

Time frame:
Baseline and up to 4 week post last dose
Reported as:
Mean · nanograms per milliliter (ng/mL)
Summary of Maximum Observed Serum Concentration (Cmax) of Belimumab at the Indicated Time Points
nanograms per milliliter (ng/mL)Belimumab 10 mg/kg IV
Day 0, 5 minutes; n= 13267996.0 ± 70598.02
Week 28, 5 minutes; n= 11312462.2 ± 95171.16
SecondarySummary of Minimum Observed Concentration (Cmin) of Belimumab at the Indicated Time Points

Trough concentration (Cmin) samples collected on the specified days are being used to assess attainment whether there was sufficient belimumab despite it being lost in the urine from the proteinuria and to check if it improved as proteinuria resolved. Analysis was performed on pre-infusion samples at weeks 2,4,8,12,28,40,52,76 and the 4 week post last-dose.

Time frame:
Baseline and up to 4 week post last dose
Reported as:
Mean · ng/mL
Summary of Minimum Observed Concentration (Cmin) of Belimumab at the Indicated Time Points
ng/mLBelimumab 10 mg/kg IV
Pre-infusion; Week 2; n= 1429940.8 ± 20918.28
Pre-infusion; Week 4; n= 1241220.9 ± 35720.14
Pre-infusion; Week 8; n= 1330350.9 ± 25505.70
Pre-infusion; Week 12; n= 1130913.7 ± 30681.42
Pre-infusion; Week 28; n= 1134904.7 ± 26388.60
Pre-infusion; Week 40; n= 1040800.6 ± 28847.86
Pre-infusion; Week 52; n= 938375.9 ± 14136.23
Pre-infusion; Week 76; n= 865655.8 ± 32873.33
4 Weeks post last-dose; n= 960497.3 ± 28074.37
SecondarySummary of Area Under the Serum Concentration-time Curve to the Last Quantifiable Concentration (AUC[0-2])

The AUC(0-2) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples for PK analysis were collected at the following time points: pre-dose (on dosing days): Days 0, 1, 4, 7, 14 and Week 4, 8, 12, 28, 40, 52, 76 and 4 week post last dose. Post-dose (5 minutes after dosing complete): Days 0 and 28. The results will be posted at later date following post hoc analysis.

Time frame:
Baseline and up to 4 week post last dose

No measurements were reported for this outcome.

SecondarySummary of Total Amount of Urine Excreted Ae(0-24)

PK parameters from the urine concentration data: urine Ae(0-24) were assessed. 24 h urine collections for PK analysis were collected after the Day 0 and Weeks 12, 28, 52, 76 doses and at the 4 week post last dose visit. A population approach was undertaken to characterize the population PK parameters and associated variability of belimumab in nephrotic participants. The population approach could have provided derived clearance of belimumab for each participant after the first dose. The population PK analysis was conducted using nonlinear mixed-effect modeling (NONMEM) or appropriate nonlinear mixed-effect analysis software. Several samples were taken pre-dose at Day 0 and some at week 12 incorrectly which affects interpretation.

Time frame:
Baseline and Up to 4 week post last dose
Reported as:
Mean · ng/hour
Summary of Total Amount of Urine Excreted Ae(0-24)
ng/hourBelimumab 10 mg/kg IV
Day 0; n= 14105826.23 ± 178943.857
Week 12; n= 1295188.14 ± 130217.976
Week 28; n= 1192997.94 ± 110142.599
Week 52; n= 9219367.96 ± 391752.377
Week 76; n= 8145645.34 ± 267292.225
4 Week post last dose; n= 67909.34 ± 16771.559
SecondaryChange From Baseline in Short Form (SF)-36 v2 Quality of Life (QoL) Questionnaire Score

Health-related quality of life was assessed through participant self-completion of the short form health survey (SF-36 version \[v2\]), a general health related quality of life metrics. Norm-based Scores (NBS) for physical functioning, role emotional, role physical were assessed. The remaining SF-36 component scores require re-scaling and therefore will be added at a later date. SF-36 was administered prior to any procedures at Weeks 12, 28, 52, 76 and 104/4 week post last dose. Item score were recorded and higher score represented better health status. Baseline is defined as Day 0 pre dose value and change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Time frame:
Baseline and up to Week 104/4 week post last dose
Reported as:
Mean · Scores on a scale
Change From Baseline in Short Form (SF)-36 v2 Quality of Life (QoL) Questionnaire Score
Scores on a scaleBelimumab 10 mg/kg IV
Physical functioning, Week 12; n= 12-4.034 ± 5.1907
Physical functioning, Week 28; n= 11-0.765 ± 3.6780
Physical functioning, Week 52; n= 90.468 ± 7.3489
Physical functioning, Week 76; n= 70.601 ± 7.9409
Physical functioning 4 Week post final dose;n=110.765 ± 11.7275
Role emotional, Week 12; n= 12-0.000 ± 10.4831
Role emotional, Week 28; n= 111.413 ± 15.1824
Role emotional, Week 52; n= 93.023 ± 11.4621
Role emotional, Week 76; n= 73.332 ± 7.2475
Role emotional, 4 Week post final dose; n= 116.007 ± 10.0413
Role physical, Week 12; n= 120.816 ± 11.0681
Role physical, Week 28; n= 113.340 ± 8.4324
Role physical, Week 52; n= 93.537 ± 9.1726
Role physical, Week 76; n= 77.697 ± 12.2803
Role physical 4 Week post final dose; n= 115.789 ± 11.4489
SecondaryNumber of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The analysis was performed on Safety Population which comprised of all participants who were randomized into the study. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, Requires hospitalization or prolongation of existing hospitalization, Results in disability/incapacity, is a congenital anomaly/birth defect, may require medical or surgical intervention, is associated with liver injury and impaired liver function.

Time frame:
Baseline and up to Week 128/6 month follow up
Reported as:
Number · Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
ParticipantsBelimumab 10 mg/kg IV
AE14
SAE3
SecondaryNumber of Participants With Abnormal Clinical Chemistry and Hematology Values

Blood samples were collected from participants for evaluation of clinical chemistry and hematology parameters. The clinical chemistry parameters included albumin, alkaline phosphatase (alk.phosph.), alanine amino transferase (ALT), aspartate amino transferase (AST), total and direct bilirubin, calcium, cholesterol, chloride, carbon dioxide, creatinine, gamma glutamyl transferase (GGT), glucose, potassium, lactate dehydrogenase (LD), magnesium, sodium, phosphorus, total protein, blood urea nitrogen (BUN) and uric acid. The hematology parameters included basophils, eosinophil, hemoglobin, hematocrit, lymphocytes, monocytes, total neutrophils, platelets, red blood cells (RBC) count and white blood cells (WBC) count. Participants were counted in the category that their value changes to (low or high) for the specific time points. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and up to Week 116/16 week follow-up visit
Reported as:
Number · Participants
Number of Participants With Abnormal Clinical Chemistry and Hematology Values
ParticipantsBelimumab 10 mg/kg IV
Albumin; Week 12; to high; n= 130
Albumin; Week 12; to low; n= 130
Albumin; Week 28; to high; n= 110
Albumin; Week 28; to low; n= 110
Albumin; Week 52; to high; n= 70
Albumin; Week 52; to low; n= 70
Albumin; Week 76; to high; n= 80
Albumin; Week 76; to low; n= 80
Albumin; Week 104; to high; n= 100
Albumin; Week 104; to low; n= 100
Albumin; 16 Week follow up; to high; n= 80
Albumin; 16 Week follow up; to low; n= 80
Alk.phosph.; Week 12; to high; n= 130
Alk.phosph.; Week 12; to low; n= 130
Alk.phosph.; Week 28; to high; n= 110
Alk.phosph.; Week 28; to low; n= 110
Alk.phosph.; Week 52; to high; n= 70
Alk.phosph.; Week 52; to low; n= 70
Alk.phosph.; Week 76; to high; n= 80
Alk.phosph.; Week 76; to low; n= 80
Alk.phosph.; Week 104; to high; n= 100
Alk.phosph.; Week 104; to low; n= 100
Alk.phosph.; 16 Week follow up; to high; n= 80
Alk.phosph.; 16 Week follow up; to low; n= 80
ALT; Week 12; to high; n= 130
ALT; Week 12; to low; n= 130
ALT; Week 28; to high; n= 110
ALT; Week 28; to low; n= 110
ALT; Week 52; to high; n= 70
ALT; Week 52; to low; n= 70
ALT; Week 76; to high; n= 80
ALT; Week 76; to low; n= 80
ALT; Week 104; to high; n= 100
ALT; Week 104; to low; n= 100
ALT; 16 Week follow up; to high; n= 80
ALT; 16 Week follow up; to low; n= 80
AST; Week 12; to high; n= 130
AST; Week 12; to low; n= 130
AST; Week 28; to high; n= 111
AST; Week 28; to low; n= 110
AST; Week 52; to high; n= 70
AST; Week 52; to low; n= 70
AST; Week 76; to high; n= 80
AST; Week 76; to low; n= 80
AST; Week 104; to high; n= 100
AST; Week 104; to low; n= 100
AST; 16 Week follow up; to high; n= 80
AST; 16 Week follow up; to low; n= 80
Direct bilirubin; Week 12; to high; n= 130
Direct bilirubin; Week 12; to low; n= 130
Direct bilirubin; Week 28; to high; n= 110
Direct bilirubin; Week 28; to low; n= 110
Direct bilirubin; Week 52; to high; n= 70
Direct bilirubin; Week 52; to low; n= 70
Direct bilirubin; Week 76; to high; n= 80
Direct bilirubin; Week 76; to low; n= 80
Direct bilirubin; Week 104; to high; n= 100
Direct bilirubin; Week 104; to low; n= 100
Direct bilirubin; 16 Week follow up; to high; n=80
Direct bilirubin; 16 Week follow up; to low; n= 80
Total bilirubin; Week 12; to high; n= 120
Total bilirubin; Week 12; to low; n= 120
Total bilirubin; Week 28; to high; n= 110
Total bilirubin; Week 28; to low; n= 110
Total bilirubin; Week 52; to high; n= 70
Total bilirubin; Week 52; to low; n= 70
Total bilirubin; Week 76; to high; n= 80
Total bilirubin; Week 76; to low; n= 80
Total bilirubin; Week 104; to high; n= 100
Total bilirubin; Week 104; to low; n= 100
Total bilirubin; 16 Week follow up; to high; n= 80
Total bilirubin; 16 Week follow up; to low; n= 80
Calcium; Week 12; to high; n= 120
Calcium; Week 12; to low; n= 120
Calcium; Week 28; to high; n= 110
Calcium; Week 28; to low; n= 110
Calcium; Week 52; to high; n= 70
Calcium; Week 52; to low; n= 70
Calcium; Week 76; to high; n= 80
Calcium; Week 76; to low; n= 80
Calcium; Week 104; to high; n= 101
Calcium; Week 104; to low; n= 101
Calcium; 16 Week follow up; to high; n= 80
Calcium; 16 Week follow up; to low; n= 80
Cholesterol; Week 12; to high; n= 130
Cholesterol; Week 12; to low; n= 130
Cholesterol; Week 28; to high; n= 110
Cholesterol; Week 28; to low; n= 110
Cholesterol; Week 52; to high; n= 70
Cholesterol; Week 52; to low; n= 70
Cholesterol; Week 76; to high; n= 80
Cholesterol; Week 76; to low; n= 80
Cholesterol; Week 104; to high; n= 100
Cholesterol; Week 104; to low; n= 100
Cholesterol; 16 Week follow up; to high; n= 80
Cholesterol; 16 Week follow up; to low; n= 80
Chloride; Week 12; to high; n= 131
Chloride; Week 12; to low; n= 130
Chloride; Week 28; to high; n= 112
Chloride; Week 28; to low; n= 110
Chloride; Week 52; to high; n= 70
Chloride; Week 52; to low; n= 70
Chloride; Week 76; to high; n= 80
Chloride; Week 76; to low; n= 80
Chloride; Week 104; to high; n= 100
Chloride; Week 104; to low; n= 100
Chloride; 16 Week follow up; to high; n= 80
Chloride; 16 Week follow up; to low; n= 80
Carbon dioxide; Week 12; to high; n= 130
Carbon dioxide; Week 12; to low; n= 131
Carbon dioxide; Week 28; to high; n= 110
Carbon dioxide; Week 28; to low; n= 113
Carbon dioxide; Week 52; to high; n= 70
Carbon dioxide; Week 52; to low; n= 70
Carbon dioxide; Week 76; to high; n= 80
Carbon dioxide; Week 76; to low; n= 80
Carbon dioxide; Week 104; to high; n= 100
Carbon dioxide; Week 104; to low; n= 101
Carbon dioxide; 16 Week follow up; to high; n= 80
Carbon dioxide; 16 Week follow up; to low; n= 80
Creatinine; Week 12; to high; n= 132
Creatinine; Week 12; to low; n= 130
Creatinine; Week 28; to high; n= 110
Creatinine; Week 28; to low; n= 110
Creatinine; Week 52; to high; n= 70
Creatinine; Week 52; to low; n= 70
Creatinine; Week 76; to high; n= 82
Creatinine; Week 76; to low; n= 81
Creatinine; Week 104; to high; n= 100
Creatinine; Week 104; to low; n= 100
Creatinine; 16 Week follow up; to high; n= 80
Creatinine; 16 Week follow up; to low; n= 80
GGT; Week 12; to high; n= 130
GGT; Week 12; to low; n= 130
GGT; Week 28; to high; n= 110
GGT; Week 28; to low; n= 110
GGT; Week 52; to high; n= 70
GGT; Week 52; to low; n= 70
GGT; Week 76; to high; n= 80
GGT; Week 76; to low; n= 80
GGT; Week 104; to high; n= 100
GGT; Week 104; to low; n= 100
GGT; 16 Week follow up; to high; n=80
GGT; 16 Week follow up; to low; n= 80
Glucose; Week 12; to high; n= 133
Glucose; Week 12; to low; n= 130
Glucose; Week 28; to high; n= 114
Glucose; Week 28; to low; n= 110
Glucose; Week 52; to high; n= 72
Glucose; Week 52; to low; n= 70
Glucose; Week 76; to high; n= 83
Glucose; Week 76; to low; n= 80
Glucose; Week 104; to high; n= 101
Glucose; Week 104; to low; n= 100
Glucose; 16 Week follow up; to high; n= 81
Glucose; 16 Week follow up; to low; n= 81
Potassium; Week 12; to high; n= 130
Potassium; Week 12; to low; n= 130
Potassium; Week 28; to high; n= 111
Potassium; Week 28; to low; n= 111
Potassium; Week 52; to high; n= 70
Potassium; Week 52; to low; n= 70
Potassium; Week 76; to high; n= 80
Potassium; Week 76; to low; n= 80
Potassium; Week 104; to high; n= 100
Potassium; Week 104; to low; n= 100
Potassium; 16 Week follow up; to high; n= 80
Potassium; 16 Week follow up; to low; n= 80
LD; Week 12; to high; n= 133
LD; Week 12; to low; n= 130
LD; Week 28; to high; n= 112
LD; Week 28; to low; n= 110
LD; Week 52; to high; n= 71
LD; Week 52; to low; n= 70
LD; Week 76; to high; n= 81
LD; Week 76; to low; n= 80
LD;Week 104; to high; n= 100
LD;Week 104; to low; n= 100
LD; 16 week follow-up; to high; n= 80
LD; 16 week follow up; to low; n= 80
Magnesium; Week 12; to high; n= 131
Magnesium; Week 12; to low; n= 130
Magnesium; Week 28; to high; n= 110
Magnesium; Week 28; to low; n= 110
Magnesium; Week 52; to high; n= 70
Magnesium; Week 52; to low; n= 70
Magnesium; Week 76; to high; n= 80
Magnesium; Week 76; to low; n= 80
Magnesium; Week 104; to high; n= 100
Magnesium; Week 104; to low; n= 100
Magnesium; 16 week follow up; to high; n= 80
Magnesium; 16 week follow up; to low; n= 80
Sodium; Week 12; to high; n= 120
Sodium; Week 12; to low; n= 120
Sodium; Week 28; to high; n= 110
Sodium; Week 28; to low; n= 111
Sodium; Week 52; to high; n= 70
Sodium; Week 52; to low; n= 71
Sodium; Week 76; to high; n= 80
Sodium; Week 76; to low; n= 81
Sodium; Week 104; to high; n= 100
Sodium; Week 104; to low; n= 100
Sodium; 16 week follow p; to high; n= 80
Sodium; 16 week follow up; to low; n= 81
Phosphorus; Week 12; to high; n= 131
Phosphorus; Week 12; to low; n= 130
Phosphorus; Week 28; to high; n= 112
Phosphorus; Week 28; to low; n= 110
Phosphorus; Week 52; to high; n= 70
Phosphorus; Week 52; to low; n= 70
Phosphorus; Week 76; to high; n= 80
Phosphorus; Week 76; to low; n= 80
Phosphorus;Week 104; to high; n= 101
Phosphorus;Week 104; to low; n= 101
Phosphorus; 16 week follow up; to high; n= 80
Phosphorus; 16 week follow up; to low; n= 80
Total protein; Week 12; to high; n= 120
Total protein; Week 12; to low; n= 120
Total protein; Week 28; to high; n= 110
Total protein; Week 28; to low; n= 110
Total protein; Week 52; to high; n= 70
Total protein; Week 52; to low; n= 71
Total protein; Week 76; to high; n= 80
Total protein; Week 76; to low; n= 80
Total protein; Week 104; to high; n= 100
Total protein; Week 104; to low; n= 100
Total protein; 16 Week follow up; to high; n= 80
Total protein; 16 Week follow up; to low; n= 80
BUN; Week 12; to high; n= 132
BUN; Week 12; to low; n= 130
BUN; Week 28; to high; n= 110
BUN; Week 28; to low; n= 110
BUN; Week 52; to high; n= 72
BUN; Week 52; to low; n= 70
BUN; Week 76; to high; n= 82
BUN; Week 76; to low; n= 80
BUN; Week 104; to high; n= 100
BUN; Week 104; to low; n= 100
BUN; 16 week follow up; to high; n= 80
BUN; 16 week follow up; to low; n= 80
Uric acid; Week 12; to high; n= 132
Uric acid; Week 12; to low; n= 132
Uric acid; Week 28; to high; n= 111
Uric acid; Week 28; to low; n= 110
Uric acid; Week 52; to high; n= 71
Uric acid; Week 52; to low; n= 70
Uric acid; Week 76; to high; n= 82
Uric acid; Week 76; to low; n= 80
Uric acid; Week 104; to high; n= 102
Uric acid; Week 104; to low; n= 100
Uric acid; 16 week follow up; to high; n= 82
Uric acid; 16 week follow up; to low; n= 80
Basophils; Week 12; to high; n= 120
Basophils; Week 12; to low; n= 120
Basophils; Week 28; to high; n= 110
Basophils; Week 28; to low; n= 110
Basophils; Week 52; to high; n= 90
Basophils; Week 52; to low; n= 90
Basophils; Week 76; to high; n= 80
Basophils; Week 76; to low; n= 80
Basophils; Week 104; to high; n= 90
Basophils; Week 104; to low; n= 90
Basophils; 16 week follow up; to high; n= 90
Basophils; 16 week follow up; to low; n= 90
Eosinophils; Week 12; to high; n= 121
Eosinophils; Week 12; to low; n= 120
Eosinophils; Week 28; to high; n= 111
Eosinophils; Week 28; to low; n= 110
Eosinophils; Week 52; to high; n= 90
Eosinophils; Week 52; to low; n= 90
Eosinophils; Week 76; to high; n= 81
Eosinophils; Week 76; to low; n= 80
Eosinophils; Week 104; to high; n= 90
Eosinophils; Week 104; to low; n= 90
Eosinophils; 16 week follow up; to high; n= 90
Eosinophils; 16 week follow up; to low; n= 90
Hemoglobin; Week 12; to high; n= 120
Hemoglobin; Week 12; to low; n= 120
Hemoglobin; Week 28; to high; n= 110
Hemoglobin; Week 28; to low; n= 110
Hemoglobin; Week 52; to high; n= 90
Hemoglobin; Week 52; to low; n= 92
Hemoglobin; Week 76; to high; n= 80
Hemoglobin; Week 76; to low; n= 81
Hemoglobin; Week 104; to high; n= 90
Hemoglobin; Week 104; to low; n= 91
Hemoglobin; 16 week follow up; to high; n= 90
Hemoglobin; 16 week follow up; to low; n= 91
Hematocrit; Week 12; to high; n= 120
Hematocrit; Week 12; to low; n= 120
Hematocrit; Week 28; to high; n= 111
Hematocrit; Week 28; to low; n= 110
Hematocrit; Week 52; to high; n= 90
Hematocrit; Week 52; to low; n= 91
Hematocrit; Week 76; to high; n= 80
Hematocrit; Week 76; to low; n= 80
Hematocrit; Week 104; to high; n= 90
Hematocrit; Week 104; to low; n= 91
Hematocrit; 16 week follow up; to high; n= 90
Hematocrit; 16 week follow up; to low; n= 91
Lymphocytes; Week 12; to high; n= 120
Lymphocytes; Week 12; to low; n= 120
Lymphocytes; Week 28; to high; n= 110
Lymphocytes; Week 28; to low; n= 110
Lymphocytes; Week 52; to high; n= 90
Lymphocytes; Week 52; to low; n= 90
Lymphocytes; Week 76; to high; n= 80
Lymphocytes; Week 76; to low; n= 80
Lymphocytes; Week 104; to high; n= 90
Lymphocytes; Week 104; to low; n= 90
Lymphocytes; 16 week follow up; to high; n= 90
Lymphocytes; 16 week follow up; to low; n= 90
Monocytes; Week 12; to high; n= 120
Monocytes; Week 12; to low; n= 120
Monocytes; Week 28; to high; n= 110
Monocytes; Week 28; to low; n= 110
Monocytes; Week 52; to high; n= 90
Monocytes; Week 52; to low; n= 90
Monocytes; Week 76; to high; n= 80
Monocytes; Week 76; to low; n= 80
Monocytes; Week 104; to high; n= 90
Monocytes; Week 104; to low; n= 90
Monocytes; 16 week follow up; to high; n= 90
Monocytes; 16 week follow up; to low; n= 90
Neutrophils; Week 12; to high; n= 121
Neutrophils; Week 12; to low; n= 120
Neutrophils; Week 28; to high; n= 110
Neutrophils; Week 28; to low; n= 110
Neutrophils; Week 52; to high; n= 90
Neutrophils; Week 52; to low; n= 90
Neutrophils; Week 76; to high; n= 80
Neutrophils; Week 76; to low; n= 80
Neutrophils; Week 104; to high; n= 92
Neutrophils; Week 104; to low; n= 90
Neutrophils; 16 week follow up; to high; n=91
Neutrophils; 16 week follow up; to low; n= 90
Platelet count; Week 12; to high; n= 123
Platelet count; Week 12; to low; n= 120
Platelet count; Week 28; to high; n= 112
Platelet count; Week 28; to low; n= 110
Platelet count; Week 52; to high; n= 90
Platelet count; Week 52; to low; n= 90
Platelet count; Week 76; to high; n= 80
Platelet count; Week 76; to low; n= 80
Platelet count; Week 104; to high; n= 91
Platelet count; Week 104; to low; n= 90
Platelet count; 16 week follow up; to high; n= 90
Platelet count; 16 week follow up; to low; n= 90
RBC; Week 12; to high; n= 120
RBC; Week 12; to low; n= 123
RBC; Week 28; to high; n= 110
RBC; Week 28; to low; n= 111
RBC; Week 52; to high; n= 90
RBC; Week 52; to low; n= 91
RBC; Week 76; to high; n= 80
RBC; Week 76; to low; n= 80
RBC; Week 104; to high; n= 90
RBC; Week 104; to low; n= 90
RBC; 16 week follow up; to high; n= 90
RBC; 16 week follow up; to low; n= 91
WBC; Week 12; to high; n= 121
WBC; Week 12; to low; n= 120
WBC; Week 28; to high; n= 110
WBC; Week 28; to low; n= 110
WBC; Week 52; to high; n= 90
WBC; Week 52; to low; n= 90
WBC; Week 76; to high; n= 80
WBC; Week 76; to low; n= 80
WBC; Week 104; to high; n= 92
WBC; Week 104; to low; n= 90
WBC; 16 week follow up; to high; n= 91
WBC; 16 week follow up; to low; n= 90
SecondaryNumber of Participants With Urinalysis Dipstick Findings

Urine samples were collected for urinalysis by dipstick method from Baseline up to Week 116/16 months follow up and number of participants with findings were presented for Baseline, Week 12, 28, 52, 76, 104/4 weeks post last-dose and Week 116/16 week follow up (WF). The urinalysis parameters included occult blood, glucose, ketones, protein. The findings were presented as trace or 1/10 g/100 milliliter (dL), trace, negative, 4+, 3+, 3+ or 1 g/dL, 2+ or 1/2 g/dL, 2+, 1+ or 1/4 g/dL and 1+. Only participants present at the specific time points were presented (represented by n=X in the category titles).

Time frame:
Baseline and up to Week 116/16 Week follow up
Reported as:
Number · Participants
Number of Participants With Urinalysis Dipstick Findings
ParticipantsBelimumab 10 mg/kg IV
Week 12; occult blood; Trace or 1/10 g/DL; n= 120
Week 12;Occult Blood; Trace; n= 121
Week 12; Occult Blood; negative; n= 122
Week 12; Occult Blood; 4+; n= 120
Week 12; Occult Blood; 3+ OR 1 G/DL; n= 120
Week 12; Occult Blood; 3+; n= 122
Week 12; Occult Blood; 2+ OR 1/2 G/DL; n= 120
Week 12; Occult Blood; 2+ ; n= 126
Week 12; Occult Blood;1+ OR 1/4 G/DL; n= 120
Week 12; Occult Blood; 1+; n= 121
Week 12; glucose; Trace or 1/10 g/DL; n= 123
Week 12;glucose; Trace; n= 120
Week 12; glucose; negative; n= 128
Week 12; glucose; 4+; n= 120
Week 12; glucose; 3+ OR 1 G/DL; n= 120
Week 12; glucose; 3+; n= 120
Week 12; glucose; 2+ OR 1/2 G/DL; n= 120
Week 12; glucose; 2+ ; n= 120
Week 12; glucose;1+ OR 1/4 G/DL; n= 121
Week 12; glucose; 1+; n= 120
Week 12; ketones; Trace or 1/10 g/DL; n= 120
Week 12; ketones; Trace; n= 120
Week 12; ketones; negative; n= 1212
Week 12; ketones; 4+; n= 120
Week 12; ketones; 3+ OR 1 G/DL; n= 120
Week 12; ketones; 3+; n= 120
Week 12; ketones; 2+ OR 1/2 G/DL; n= 120
Week 12; ketones; 2+ ; n= 120
Week 12; ketones;1+ OR 1/4 G/DL; n= 120
Week 12; ketones; 1+; n= 120
Week 12; protein; Trace or 1/10 g/DL; n= 120
Week 12; Protein; Trace; n= 120
Week 12; Protein; negative; n= 120
Week 12; Protein; 4+; n= 120
Week 12; Protein; 3+ OR 1 G/DL; n= 120
Week 12; Protein; 3+; n= 128
Week 12; Protein; 2+ OR 1/2 G/DL; n= 120
Week 12; Protein; 2+ ; n= 123
Week 12; Protein;1+ OR 1/4 G/DL; n= 120
Week 12; Protein; 1+; n= 121
Week 28; occult blood; Trace or 1/10 g/DL; n= 110
Week 28;Occult Blood; Trace; n= 112
Week 28; Occult Blood; negative; n= 111
Week 28; Occult Blood; 4+; n= 110
Week 28; Occult Blood; 3+ OR 1 G/DL; n= 110
Week 28; Occult Blood; 3+; n= 110
Week 28; Occult Blood; 2+ OR 1/2 G/DL; n= 110
Week 28; Occult Blood; 2+ ; n= 114
Week 28; Occult Blood;1+ OR 1/4 G/DL; n= 110
Week 28; Occult Blood; 1+; n= 114
Week 28; glucose; Trace or 1/10 g/DL; n= 111
Week 28;glucose; Trace; n= 110
Week 28; glucose; negative; n= 119
Week 28; glucose; 4+; n= 110
Week 28; glucose; 3+ OR 1 G/DL; n= 110
Week 28; glucose; 3+; n= 110
Week 28; glucose; 2+ OR 1/2 G/DL; n= 110
Week 28; glucose; 2+ ; n= 110
Week 28; glucose;1+ OR 1/4 G/DL; n= 111
Week 28; glucose; 1+; n= 110
Week 28; ketones; Trace or 1/10 g/DL; n= 110
Week 28; ketones; Trace; n= 110
Week 28; ketones; negative; n= 1111
Week 28; ketones; 4+; n= 110
Week 28; ketones; 3+ OR 1 G/DL; n= 110
Week 28; ketones; 3+; n= 110
Week 28; ketones; 2+ OR 1/2 G/DL; n= 110
Week 28; ketones; 2+ ; n= 110
Week 28; ketones;1+ OR 1/4 G/DL; n= 110
Week 28; ketones; 1+; n= 110
Week 28; protein; Trace or 1/10 g/DL; n= 110
Week 28; Protein; Trace; n= 110
Week 28; Protein; negative; n= 110
Week 28; protein; 4+; n= 110
Week 28; Protein; 3+ OR 1 G/DL; n= 110
Week 28; Protein; 3+; n= 1110
Week 28; Protein; 2+ OR 1/2 G/DL; n= 110
Week 28; Protein; 2+ ; n= 111
Week 28; Protein;1+ OR 1/4 G/DL; n= 110
Week 28; Protein; 1+; n= 110
Week 52; occult blood; Trace or 1/10 g/DL; n= 90
Week 52;Occult Blood; Trace; n= 92
Week 52; Occult Blood; negative; n= 93
Week 52; Occult Blood; 4+; n= 90
Week 52; Occult Blood; 3+ OR 1 G/DL; n= 90
Week 52; Occult Blood; 3+; n= 90
Week 52; Occult Blood; 2+ OR 1/2 G/DL; n= 90
Week 52; Occult Blood; 2+ ; n= 94
Week 52; Occult Blood;1+ OR 1/4 G/DL; n= 90
Week 52; Occult Blood; 1+; n= 90
Week 52; glucose; Trace or 1/10 g/DL; n= 92
Week 52;glucose; Trace; n= 90
Week 52; glucose; negative; n= 97
Week 52; glucose; 4+; n= 90
Week 52; glucose; 3+ OR 1 G/DL; n= 90
Week 52; glucose; 3+; n= 90
Week 52; glucose; 2+ OR 1/2 G/DL; n= 90
Week 52; glucose; 2+ ; n= 90
Week 52; glucose;1+ OR 1/4 G/DL; n= 90
Week 52; glucose; 1+; n= 90
Week 52; ketones; Trace or 1/10 g/DL; n= 90
Week 52; ketones; Trace; n= 90
Week 52; ketones; negative; n= 99
Week 52; ketones; 4+; n= 90
Week 52; ketones; 3+ OR 1 G/DL; n= 90
Week 52; ketones; 3+; n= 90
Week 52; ketones; 2+ OR 1/2 G/DL; n= 90
Week 52; ketones; 2+ ; n= 90
Week 52; ketones;1+ OR 1/4 G/DL; n= 90
Week 52; ketones; 1+; n= 90
Week 52; protein; Trace or 1/10 g/DL; n= 90
Week 52; Protein; Trace; n= 90
Week 52; Protein; negative; n= 90
Week 52; protein; 4+; n= 90
Week 52; Protein; 3+ OR 1 G/DL; n= 90
Week 52; Protein; 3+; n= 94
Week 52; Protein; 2+ OR 1/2 G/DL; n= 90
Week 52; Protein; 2+ ; n= 93
Week 52; Protein;1+ OR 1/4 G/DL; n= 90
Week 52; Protein; 1+; n= 92
Week 76; occult blood; Trace or 1/10 g/DL;n=70
Week 76;Occult Blood; Trace; n= 73
Week 76; Occult Blood; negative; n= 73
Week 76; Occult Blood; 4+; n= 70
Week 76; Occult Blood; 3+ OR 1 G/DL; n= 70
Week 76; Occult Blood; 3+; n= 70
Week 76; Occult Blood; 2+ OR 1/2 G/DL; n= 70
Week 76; Occult Blood; 2+ ; n= 70
Week 76; Occult Blood;1+ OR 1/4 G/DL; n= 70
Week 76; Occult Blood; 1+; n= 71
Week 76; glucose; Trace or 1/10 g/DL; n= 72
Week 76;glucose; Trace; n= 70
Week 76; glucose; negative; n= 75
Week 76; glucose; 4+; n= 70
Week 76; glucose; 3+ OR 1 G/DL; n= 70
Week 76; glucose; 3+; n= 70
Week 76; glucose; 2+ OR 1/2 G/DL; n= 70
Week 76; glucose; 2+ ; n= 70
Week 76; glucose;1+ OR 1/4 G/DL; n= 70
Week 76; glucose; 1+; n= 70
Week 76; ketones; Trace or 1/10 g/DL; n= 70
Week 76; ketones; Trace; n= 70
Week 76; ketones; negative; n= 77
Week 76; ketones; 4+; n= 70
Week 76; ketones; 3+ OR 1 G/DL; n= 70
Week 76; ketones; 3+; n= 70
Week 76; ketones; 2+ OR 1/2 G/DL; n= 70
Week 76; ketones; 2+ ; n= 70
Week 76; ketones;1+ OR 1/4 G/DL; n= 70
Week 76; ketones; 1+; n= 70
Week 76; protein; Trace or 1/10 g/DL; n= 70
Week 76; Protein; Trace; n= 70
Week 76; Protein; negative; n= 71
Week 76; protein; 4+; n= 70
Week 76; Protein; 3+ OR 1 G/DL; n= 70
Week 76; Protein; 3+; n= 71
Week 76; Protein; 2+ OR 1/2 G/DL; n= 70
Week 76; Protein; 2+ ; n= 74
Week 76; Protein;1+ OR 1/4 G/DL; n= 70
Week 76; Protein; 1+; n= 71
Week 104; occult blood; Trace or 1/10 g/DL;n=100
Week 104;Occult Blood; Trace; n= 100
Week 104; Occult Blood; negative; n= 108
Week 104; Occult Blood; 4+; n= 100
Week 104; Occult Blood; 3+ OR 1 G/DL; n= 100
Week 104; Occult Blood; 3+; n= 100
Week 104; Occult Blood; 2+ OR 1/2 G/DL; n= 100
Week 104; Occult Blood; 2+ ; n=101
Week 104; Occult Blood;1+ OR 1/4 G/DL; n= 100
Week 104; Occult Blood; 1+; n= 101
Week 104; glucose; Trace or 1/10 g/DL; n= 102
Week 104 ;glucose; Trace; n= 100
Week 104; glucose; negative; n= 107
Week 104; glucose; 4+; n= 100
Week 104; glucose; 3+ OR 1 G/DL; n= 100
Week 104; glucose; 3+; n= 100
Week 104; glucose; 2+ OR 1/2 G/DL; n= 100
Week 104; glucose; 2+ ; n= 100
Week 104; glucose;1+ OR 1/4 G/DL; n= 101
Week 104; glucose; 1+; n= 100
Week 104; ketones; Trace or 1/10 g/DL; n= 100
Week 104; ketones; Trace; n= 100
Week 104; ketones; negative; n= 1010
Week 104; ketones; 4+; n= 100
Week 104; ketones; 3+ OR 1 G/DL; n= 100
Week 104; ketones; 3+; n= 100
Week 104; ketones; 2+ OR 1/2 G/DL; n= 100
Week 104; ketones; 2+ ; n= 100
Week 104; ketones;1+ OR 1/4 G/DL; n= 100
Week 104; ketones; 1+; n= 100
Week 104; protein; Trace or 1/10 g/DL; n= 100
Week 104; Protein; Trace; n= 100
Week 104; Protein; negative; n= 101
Week 104; protein; 4+; n= 100
Week 104; Protein; 3+ OR 1 G/DL; n= 100
Week 104; Protein; 3+; n= 103
Week 104; Protein; 2+ OR 1/2 G/DL; n= 100
Week 104; Protein; 2+ ; n= 106
Week 104; Protein;1+ OR 1/4 G/DL; n= 100
Week 104; Protein; 1+; n= 100
16 WF; Occult blood; TRACE OR 1/10 G/DL; n= 90
16 WF; Occult blood; TRACE; n= 92
16 WF; Occult blood; NEGATIVE; n= 96
16 WF; Occult blood; 4+; n= 90
16 WF; Occult blood; 3+ OR 1 G/DL; n= 90
16 WF; Occult blood; 3+; n= 90
16 WF; Occult blood; 2+ OR 1/2 G/DL; n= 90
16 WF; Occult blood; 2+; n= 91
16 WF; Occult blood; 1+ OR 1/4 G/DL; n= 90
16 WF; Occult blood; 1+; n= 90
16 WF; Glucose; TRACE OR 1/10 G/DL; n= 91
16 WF; Glucose; TRACE; n= 90
16 WF; Glucose; negative; n= 97
16 WF; Glucose; 4+; n= 90
16 WF; Glucose; 3+ OR 1 G/DL; n= 90
16 WF; Glucose; 3+; n= 90
16 WF; Glucose; 2+ OR 1/2 G/DL; n= 91
16 WF; Glucose; 2+; n= 90
16 WF; Glucose; 1+ OR 1/4 G/DL; n=90
16 WF; Glucose; 1+; n=90
16 WF; Ketones; TRACE OR 1/10 G/DL; n= 90
16 WF; Ketones; TRACE; n= 90
16 WF; Ketones; negative; n= 99
16 WF; Ketones; 4+; n= 90
16 WF; Ketones; 3+ OR 1 G/DL; n= 90
16 WF; Ketones; 3+; n= 90
16 WF; Ketones; 2+ OR 1/2 G/DL; n= 90
16 WF; Ketones; 2+; n= 90
16 WF; Ketones; 1+ OR 1/4 G/DL; n= 90
16 WF; Ketones; 1+; n= 90
16 WF; Protein; TRACE OR 1/10 G/DL; n= 90
16 WF; Protein; TRACE; n= 91
16 WF; Protein; negative; n= 90
16 WF; Protein; 4+; n= 90
16 WF; Protein; 3+ OR 1 G/DL; n= 90
16 WF; Protein; 3+; n= 93
16 WF; Protein; 2+ OR 1/2 G/DL; n= 90
16 WF; Protein; 2+; n= 94
16 WF; Protein; 1+ OR 1/4 G/DL; n= 90
16 WF; Protein; 1+; n= 91
SecondaryChange From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

SBP and DBP were measured from Baseline throughout the treatment period up to Week 116/ 16 week follow-up visit. The Baseline value was taken at Day 0 pre dose and change from Baseline was defined as post dose visit value minus Baseline value. Mean and standard deviation (SD) were measured and presented for Week 12, 28, 52, 76, 104 withdrawn visit, 4 Week post last dose and 16 Week follow-up visit. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Time frame:
Baseline and up to week 116/16 week follow-up visit
Reported as:
Mean · millimeter of mercury (mmHg)
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
millimeter of mercury (mmHg)Belimumab 10 mg/kg IV
Week 12; SBP; n= 12-4.2 ± 17.23
Week 28; SBP; n= 11-5.8 ± 18.14
Week 52; SBP; n= 9-1.9 ± 18.66
Week 76; SBP; n= 8-1.3 ± 11.30
4 Week post last dose; SBP; n= 10-12.2 ± 11.78
16 Week follow up; SBP; n= 9-7.4 ± 15.72
Week 104 withdrawn visit; SBP; n= 2-1.0 ± 5.66
Week 12; DBP; n= 123.8 ± 12.94
Week 28; DBP; n= 110.8 ± 10.75
Week 52; DBP; n= 91.2 ± 11.87
Week 76; DBP; n= 82.8 ± 9.68
4 Week post last dose; DBP; n= 10-3.3 ± 9.87
16 Week follow up; DBP; n= 92.4 ± 14.98
Week 104 withdrawn visit; DBP; n= 25.5 ± 2.12
SecondaryChange From Baseline in Pulse Rate

Pulse rate was measured from Baseline throughout the treatment period up to Week 116/ 16 week follow-up visit. The Baseline value was taken at Day 0 pre dose and change from Baseline was defined as post dose visit value minus Baseline value. Mean and standard deviation (SD) were measured and presented for Week 12, 28, 52, 76, 104 withdrawn visit, 4 Week post last dose and 16 Week post last dose visits. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Time frame:
Baseline and up to Week 116/16 week follow-up visit
Reported as:
Mean · Beats per minute
Change From Baseline in Pulse Rate
Beats per minuteBelimumab 10 mg/kg IV
Week 12; n= 12-0.7 ± 11.40
Week 28; n= 111.0 ± 7.90
Week 52; n= 9-1.7 ± 13.11
Week 76; n= 8-2.3 ± 15.77
4 Week post last dose; n= 10-2.8 ± 15.33
16 Week follow up; n= 9-0.9 ± 16.72
Week 104 withdrawn visit; n= 25.0 ± 7.07
SecondaryChange From Baseline in Temperature

Temperature was measured from Baseline throughout the treatment period up to Week 116/ 16 week follow-up visit. The Baseline value was taken at Day 0 pre dose and change from Baseline was defined as post dose visit value minus Baseline value. Mean and standard deviation (SD) were measured and presented for Week 12, 28, 52, 76, 104 withdrawn visit, 4 Week post last dose and 16 week post last dose visits. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Time frame:
Baseline and up to Week 116/16 week follow-up visit
Reported as:
Mean · Celsius
Change From Baseline in Temperature
CelsiusBelimumab 10 mg/kg IV
Week 12; n= 12-0.09 ± 0.591
Week 28; n= 11-0.00 ± 0.453
Week 52; n= 9-0.11 ± 0.639
Week 76; n= 8-0.17 ± 0.486
4 Week post last dose; n= 8-0.06 ± 0.604
16 Week follow up; n= 60.30 ± 0.424
Week 104 withdrawn visit; n= 20.15 ± 0.353
SecondaryNumber of Participants With Positive Immunogenicity Findings

Blood samples of participants were collected pre-dose on Weeks 0, 12, 28, 40, 52, 76, 4 week post last dose and 16 week post last dose visit for belimumab immunogenicity assay. No participants showed positive immunogenicity findings.

Time frame:
Baseline and up to Week 116/16 week follow-up visit
Reported as:
Number · Participants
Number of Participants With Positive Immunogenicity Findings
ParticipantsBelimumab 10 mg/kg IV
Number of Participants With Positive Immunogenicity Findings0
SecondaryUrine Membrane Attack Complex (MAC) Levels

Urine membrane attack complex was assayed quantitatively by ELISA method. Urine MAC samples were collected at Day 0 and Weeks 8, 28, 52, 76 and 4 week post last dose. Results were normalized using urine creatinine concentration to adjust for urine dilution. Endpoint was moved to 'Exploratory' in Protocol amendment 5 as risk of availability of functioning assay for urine membrane attack complex was noted. No assay was subsequently found and samples were not analyzed

Time frame:
Baseline and up to 4 week post last dose

No measurements were reported for this outcome.

SecondaryChange From Baseline in Urine Membrane Attack Complex (MAC)

Urine membrane attack complex will be assayed quantitatively by ELISA method. Urine MAC samples are being collected at Day 0 and Weeks 8, 28, 52, 76 and 4 week post last dose. Results will be normalized using urine creatinine concentration to adjust for urine dilution, before calculation of the ratio as value at time point divided by value at Baseline (Day 0). Endpoint was changed to 'exploratory' as risk of availability of functioning assay for urine membrane attack complex was noted. No assay was subsequently found and samples were not analyzed.

Time frame:
Baseline and up to 4 week post last dose

No measurements were reported for this outcome.

SecondaryChange From Baseline in B Cell and T Cell Markers Concentration

B cell Facs panels were used to measure changes over the course of therapy in B cell subsets such as transitional, naïve, memory and plasma B cell compartments by percent of the B cell compartments and absolute numbers. T cell Facs panel were used to measure changes in T cell subsets, such as T regs and CD4+ and CD8+ T cells, in terms of numbers and expression of activation markers to establish if B cell targeting with belimumab affects the T cell compartment perhaps through limiting B cell antigen presentation or cytokine release. Baseline is defined as Day 0 value and change from Baseline was calculated as ratio of post-Baseline value divided by the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame:
Baseline and up to Week 128/6 month post last dose
Reported as:
Geometric mean · Ratio
Change From Baseline in B Cell and T Cell Markers Concentration
RatioBelimumab 10 mg/kg IV
CD19+; Week 8; n= 120.7221 ± 82.1
CD19+; Week 16; n= 110.9209 ± 63.6
CD19+; Week 28; n= 101.0049 ± 71.6
CD19+; Week 104; n= 100.5193 ± 156.2
CD19+; 6 month follow up; n= 70.3828 ± 185.7
CD19+ CD24b+ CD38b+ CD27-; Week 8; n= 120.2352 ± 340.0
CD19+ CD24b+ CD38b+ CD27-; Week 16; n= 110.6228 ± 316.7
CD19+ CD24b+ CD38b+ CD27-; Week 28; n= 100.6119 ± 656.0
CD19+ CD24b+ CD38b+ CD27-; Week 104; n= 100.3582 ± 405.1
CD19+ CD24b+ CD38b+ CD27-; 6 month follow up; n= 71.6471 ± 534.0
CD19+ CD27- IgD+; Week 8; n= 120.3490 ± 131.6
CD19+ CD27- IgD+; Week 16; n= 110.4486 ± 94.7
CD19+ CD27- IgD+; Week 28; n= 100.4561 ± 82.5
CD19+ CD27- IgD+; Week 104; n= 100.1808 ± 298.6
CD19+ CD27- IgD+; 6 month follow up; n= 70.3278 ± 189.2
CD19+ CD27-; Week 8; n= 120.4074 ± 109.2
CD19+ CD27-; Week 16; n= 110.5079 ± 88.1
CD19+ CD27-; Week 28; n= 100.5165 ± 76.5
CD19+ CD27-; Week 104; n= 100.2602 ± 236.9
CD19+ CD27-; 6 month follow up; n= 70.3756 ± 186.0
CD19lo CD38hi CD27hi; Week 8; n= 120.5982 ± 555.4
CD19lo CD38hi CD27hi; Week 16; n= 110.4128 ± 1085.7
CD19lo CD38hi CD27hi; Week 28; n= 100.4481 ± 651.6
CD19lo CD38hi CD27hi; Week 104; n= 100.2615 ± 238.8
CD19lo CD38hi CD27hi; 6 month follow up; n= 70.0647 ± 1269.7
CD19+ CD24+ CD27+ ; Week 8; n= 122.0747 ± 65.3
CD19+ CD24+ CD27+ ; Week 16; n= 112.4161 ± 61.2
CD19+ CD24+ CD27+ ; Week 28; n= 103.1294 ± 64.2
CD19+ CD24+ CD27+ ; Week 104; n= 100.6089 ± 104014.8
CD19+ CD24+ CD27+ ; 6 month follow up; n= 70.7952 ± 328.6
CD19+CD27+; Week 8; n= 121.9195 ± 69.9
CD19+CD27+; Week 16; n= 112.3132 ± 62.7
CD19+CD27+; Week 28; n= 103.1352 ± 65.6
CD19+CD27+; Week 104; n= 101.3273 ± 127.7
CD19+CD27+; 6 month follow up; n= 70.3338 ± 158.2
CD19+CD27+IgD; Week 8; n= 121.9365 ± 69.6
CD19+CD27+IgD; Week 16; n= 112.3147 ± 75.1
CD19+CD27+IgD; Week 28; n= 103.2313 ± 51.1
CD19+CD27+IgD; Week 104; n= 101.2814 ± 102.3
CD19+CD27+IgD; 6 month follow up; n= 70.2413 ± 163.9
CD19+CD27+IgD-; Week 8; n= 121.8846 ± 67.7
CD19+CD27+IgD-; Week 16; n= 112.2113 ± 70.4
CD19+CD27+IgD-; Week 28; n= 103.0478 ± 73.2
CD19+CD27+IgD-; Week 104; n= 101.3051 ± 147.1
CD19+CD27+IgD-; 6 month follow up; n= 70.3440 ± 163.8
CD4+ CD25hi CD45RA- IL7Rhi; Week 8; n= 120.7010 ± 86.7
CD4+ CD25hi CD45RA- IL7Rhi; Week 16; n= 100.5340 ± 221.3
CD4+ CD25hi CD45RA- IL7Rhi; Week 28; n= 90.5718 ± 669.2
CD4+ CD25hi CD45RA- IL7Rhi; Week 104; n= 104.1865 ± 509.4
CD4+ CD25hi CD45RA- IL7Rh; 6 month follow up; n= 71.8067 ± 1456.7
CD4+ CD45RA- IL-7Rhi; Week 8; n= 121.4174 ± 19513.4
CD4+ CD45RA- IL-7Rhi; Week 16; n= 101.8613 ± 99527.6
CD4+ CD45RA- IL-7Rhi; Week 28; n=92.8378 ± 49940.7
CD4+ CD45RA- IL-7Rhi; Week 104; n= 100.1517 ± 33534.3
CD4+ CD45RA- IL-7Rhi; 6 month follow-up; n= 70.3532 ± 966.4
CD4+ CD25hi xIL-7Rlo; Week 8; n= 120.7285 ± 85.7
CD4+ CD25hi xIL-7Rlo; Week 16; n= 110.6232 ± 317.6
CD4+ CD25hi xIL-7Rlo; Week 28; n= 100.7010 ± 961.5
CD4+ CD25hi xIL-7Rlo; Week 104; n= 103.1025 ± 932.7
CD4+ CD25hi xIL-7Rlo; 6 month follow-up; n= 72.0827 ± 832.7
CD4+ CD25hi IL-7Rlo; Week 8; 122.3001 ± 29702.5
CD4+ CD25hi IL-7Rlo; Week 16; n= 102.9023 ± 136702.6
CD4+ CD25hi IL-7Rlo; Week 28; n= 93.3453 ± 35372.4
CD4+ CD25hi IL-7Rlo; Week 104; n= 100.3410 ± 72506.2
CD4+ CD25hi IL-7Rlo; 6 month follow up; n= 70.9978 ± 32.7
CD4+ CD45RA-; Week 8; n= 120.7532 ± 44.5
CD4+ CD45RA-; Week 16; n= 110.7638 ± 55.4
CD4+ CD45RA-; Week 28; n= 100.9032 ± 71.1
CD4+ CD45RA-; 104; n= 100.9750 ± 95.8
CD4+ CD45RA-; 6 month follow up; n= 71.0792 ± 90.0
SecondaryChange From Baseline in Cytokines/Chemokine

Cytokine/chemokine associated with T helper skewing or autoimmune pathology will be analyzed using Luminex, ELISA. Serum analyte quantification were used to confirm altered protein levels of any gene expression increases or decreases identified by transcriptomic analysis. Endpoint was moved to 'Exploratory' in Protocol amendment 5 as benefits of assessing cytokines was deemed low. Samples were not analyzed.

Time frame:
Baseline and up to Week 104/4 week post last dose

No measurements were reported for this outcome.

SecondarySerum BLys Levels

Free BLyS protein were analyzed using an ELISA. Serum samples were collected before treatment and after belimumab washout at Week 0 and Week 116/16 week follow-up visit.

Time frame:
Baseline and Week 116/16 week follow-up visit
Reported as:
Geometric mean · pg/mL
Serum BLys Levels
pg/mLBelimumab 10 mg/kg IV
Day 0; n= 14969.9595 ± 16.8
16 week follow up; n= 812357.5558 ± 123.3
SecondaryUrine BLys Levels as a Ratio to Creatinine

B lymphocyte stimulator (BLyS) normalized by creatinine as a ratio of BLyS: creatinine. Free BLyS protein is being analyzed using an ELISA. Urine samples are being collected before treatment and after belimumab washout at Week 0 and Week 116/16 week follow-up visit. Only raw BLyS values available and unable to be assessed due to lack of comparison to a creatinine as a urine concentration marker.

Time frame:
Baseline and Week 116/16 week follow-up visit

No measurements were reported for this outcome.

Adverse events

Collected over On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) are presented from the start of study treatment up to end of study.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Belimumab 10 mg/kg IV—3/14 (21.4%)14/14 (100%)
Most frequent serious events
Most frequent serious events
EventBelimumab 10 mg/kg IV
CellulitisInfections and infestations1/14
Weight decreasedInvestigations1/14
EmbolismVascular disorders1/14
Most frequent other events
Showing 10 of 71
Most frequent other events
EventBelimumab 10 mg/kg IV
Upper respiratory tract infectionInfections and infestations6/14
Viral upper respiratory tract infectionInfections and infestations5/14
Muscle spasmsMusculoskeletal and connective tissue disorders4/14
Lower respiratory tract infectionInfections and infestations2/14
RhinitisInfections and infestations2/14
DiarrhoeaGastrointestinal disorders2/14
DyspepsiaGastrointestinal disorders2/14
ArthralgiaMusculoskeletal and connective tissue disorders2/14
Pain in extremityMusculoskeletal and connective tissue disorders2/14
HeadacheNervous system disorders2/14

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Belimumab 10 mg/kg IV
Mean46.1 ± 13.30
Sex: Female, Male
Sex: Female, Male(Participants)Belimumab 10 mg/kg IV
Female3
Male11
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Belimumab 10 mg/kg IV
Asian - Central/South Asian Heritage4
White- White/Caucasian/European Heritage9
Unknown1
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Study locations

8 sites
  • GSK Investigational Site
    Exeter, Devon EX2 5DW, United Kingdom
  • GSK Investigational Site
    Stevenage, Hertfordshire SG1 4AB, United Kingdom
  • GSK Investigational Site
    Cambridge, CB2 0QQ, United Kingdom
  • GSK Investigational Site
    Glasgow, G11 6NT, United Kingdom
  • GSK Investigational Site
    Manchester, M13 9WL, United Kingdom
  • GSK Investigational Site
    Reading, RG1 5AN, United Kingdom
  • GSK Investigational Site
    Salford, M6 8HD, United Kingdom
  • GSK Investigational Site
    Whitechapel, London, E1 1BB, United Kingdom
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 13, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01610492
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Jun 4, 2012
Start date
Jul 1, 2012
Primary completion
Sep 24, 2014
Completion
Sep 14, 2016
Results posted
Jun 1, 2015
Last update
Oct 13, 2017

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Sep 2017. You cannot join it, but the record below documents what was studied.

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

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