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OpenTrials
Completed

NCT Number: NCT01610492

A Study of Belimumab in Idiopathic Membranous Glomerulonephropathy

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.

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Key information

Conditions

Glomerulonephritis, Membranous Autoimmune Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glomerulonephritis Immune System Diseases Kidney Diseases Male Urogenital Diseases Nephritis Urogenital Diseases Urologic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

GSK Investigational Site, Exeter, Devon, United Kingdom

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

  • 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.

Treatment and study plan

Belimumab

Drug

10mg/kg administered intravenously

Primary outcomes

  1. Change From Baseline in Proteinuria Levels at Week 28

    Time frame: Baseline and 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.

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

    Time frame: Baseline and 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.

Secondary outcomes

  1. Proteinuria Levels at the Indicated Time Points

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

    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).

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

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

    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).

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

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

    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).

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

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

    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).

  5. Number of Participants With Complete or Partial Remission

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

    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).

  6. Time to Complete or Partial Remission

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

    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.

  7. Duration of Complete or Partial Remission

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

    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.

  8. Number of Participants With PLA2R Autoantibody Remission

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

    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).

  9. Time to Anti-PLA2R Autoantibody Remission

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

    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.

  10. Number of Participants With Anti-PLA2R Autoantibody Relapse

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

    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).

  11. eGFR Levels at the Indicated Time Points

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

    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).

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

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

    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).

  13. Serum Creatinine Levels at the Indicated Time Points

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

    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).

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

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

    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).

  15. Serum Albumin Levels at Indicated Time Points

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

    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).

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

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

    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).

  17. Serum Cholesterol Levels at Indicated Time Points

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

    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).

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

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

    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).

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

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

    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).

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

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

    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).

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

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

    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).

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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).

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

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

    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.

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

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

    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).

  29. Number of Participants With Urinalysis Dipstick Findings

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

    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).

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

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

    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).

  31. Change From Baseline in Pulse Rate

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

    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).

  32. Change From Baseline in Temperature

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

    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).

  33. Number of Participants With Positive Immunogenicity Findings

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

    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.

  34. Urine Membrane Attack Complex (MAC) Levels

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

    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

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

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

    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.

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

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

    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).

  37. Change From Baseline in Cytokines/Chemokine

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

    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.

  38. Serum BLys Levels

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

    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.

  39. Urine BLys Levels as a Ratio to Creatinine

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

    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.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

BEL116472. A 2 Year Mechanistic Study of Belimumab in Idiopathic Membranous Glomerulonephropathy

Important dates

Study start
2012
Primary completion
2014
Study completion
2016
First posted
Jun 4, 2012
Registry last updated
Oct 13, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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