A Study of Belimumab in Idiopathic Membranous Glomerulonephropathy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01610492
First received: May 31, 2012
Last updated: April 30, 2015
Last verified: March 2015

May 31, 2012
April 30, 2015
July 2012
September 2014   (final data collection date for primary outcome measure)
  • Change from Baseline in proteinuria levels at Week 28 [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]
    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.
  • Change from Baseline in anti-phospholipase A2 receptor (PLA2R) autoantibody titres at Week 28 [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]
    PLA2R autoantibody titres 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. The ratio is defined as the Week 28 value divided by the Baseline value.
  • Change from baseline in proteinuria levels at week 28 [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
    To evaluate whether belimumab can modulate proteinuria in IMGN.
  • Change from baseline in anti-PLA2R autoantibody titres at week 28 [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
    To evaluate whether belimumab can modulate anti-PLA2R autoantibodies in patients with detectable baseline levels of these antibodies.
  • Change from baseline in urine levels of belimumab at week 28 [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01610492 on ClinicalTrials.gov Archive Site
  • Proteinuria levels at the indicated time points [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]
    Proteinuria based on urinary protein creatinine ratio (PCR) was measured from 2 consecutive 24 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 Day 0 value.
  • Change from Baseline in proteinuria levels at the indicated time points [ Time Frame: Baseline and Weeks 12, 28, 52, 76 and 104/4 week post last dose ] [ Designated as safety issue: No ]
    Proteinuria is being assessed at Weeks 0, 4, 8, 12, 16, 20, 24, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104/4 week post last dose and at the 16 week and 6 month follow-up visits. Proteinuria measurements are being based on urinary protein creatinine ratio measurements spot urine samples. For other key time points, Weeks 12, 52, 76 and 4 week post last dose, they are the mean of the PCR from a pre-dose spot urine sample and from a 24 h post-dose or post visit urine collection. Baseline is defined as the mean of the pre and post dosing Day 0 values from 2 consecutive 24 h urine collections. The ratio is defined as the post-Baseline value divided by the Baseline value. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Anti-phospholipase A2 receptor (PLA2R) autoantibody titres at the indicated time points [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]
    PLA2R autoantibody titres 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.
  • Change from Baseline in anti-PLA2R autoantibody titres at the indicated time points [ Time Frame: Baseline and Weeks 12, 28, 52, 76 and 104/4 week post last dose ] [ Designated as safety issue: No ]
    PLA2R autoantibody titres in serum are being analyzed by means of a validated anti- PLA2R ELISA from EuroImmun. Anti-PLA2R autoantibody blood samples are being collected at Weeks 0, 4, 8, 12, 16, 20, 24, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104/4 week post last dose and 16 week and 6 month follow-up visits. Baseline is defined as the Day 0 value. Ratio is defined as the post-Baseline value divided by the Baseline value. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Change from Baseline in urine levels of belimumab at the indicated time points [ Time Frame: Baseline and Weeks 12, 28, 52, 76 and 4 week post last dose ] [ Designated as safety issue: No ]
    24 h urine samples are being collected for pharmacokinetic analysis of belimumab, after the Day 0 and Weeks 12, 28, 52, 76 doses and at the 4 week post last dose visit. Baseline is defined as the Day 0 value. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Incidence of complete or partial remission [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Complete remission is defined as PCR <30 milligrams per millimoles (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% from Day 0 Baseline, together with no worsening in renal function (eGFR reduction from Baseline <15%). The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Time to complete or partial remission [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Time to complete or partial remission and time of proteinuria are being 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%). 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 worsening in renal function (eGFR reduction from Baseline <15%). The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Duration of complete or partial remission [ Time Frame: Baseline and up to Week 104/ 4 week post last dose ] [ Designated as safety issue: No ]
    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%). 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 worsening in renal function (eGFR reduction from Baseline <15%). The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Incidence of proteinuria relapse [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Incidence of proteinuria relapse is defined as participants with PCR >350 mg/mmol and an increase of 50% from the lowest remission level, in those participants who had previously achieved any type of remission. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Incidence of full/partial remission for anti-PLA2R autoantibody [ Time Frame: Baseline and up to Week 104/4 Week post last dose ] [ Designated as safety issue: No ]
    Incidence of anti-PLA2R autoantibody remission: full response is defined as antibody undetectable, partial response is defined as reduction in titres by 50%. For anti PLA2R autoantibody data, log transformation is being applied before the formal analyses. Anti-PLA2R autoantibody blood samples are being collected at Weeks 0, 4, 8, 12, 16, 20, 24, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104/4 week post last dose and 16 week and 6 month follow-up visits. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Time to anti-PLA2R autoantibody remission [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Time to anti-PLA2R autoantibody remission - full response with antibody undetectable. Anti-PLA2R autoantibody blood samples are being collected at Weeks 0, 4, 8, 12, 16, 20, 24, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104/4 week post last dose and 16 week and 6 month follow-up visits. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Incidence of anti-PLA2R autoantibody relapse [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Incidence of anti-PLA2R autoantibody relapse defined as antibody detectable after previously undetectable. Anti-PLA2R autoantibody blood samples are being collected at Weeks 0, 4, 8, 12, 16, 20, 24, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104/4 week post last dose and 16 week and 6 month follow-up visits. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • eGFR levels at the indicated time points [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    eGFR is being 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. For the end of therapy (Week 104/4 week post last dose assessment), eGFR is being analyzed at both Weeks 100 and 104 (or last dose and 4 week post last dose visits for participants withdrawing early from study treatment), and the mean is being calculated. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods. Milliliters per minute per 1.73 meter squared (ml/min/1.73m^2).
  • Change from Baseline in eGFR levels at the indicated time points [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    eGFR is being 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. For the end of therapy (Week 104/4 week post last dose assessment), eGFR is being analyzed at both Weeks 100 and 104 (or last dose and 4 week post last dose visits for participants withdrawing early from study treatment), and the mean is being calculated. The ratio is defined as the value at the defined time point divided by the Baseline value. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Serum creatinine levels at the indicated time points [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Clinical chemistry laboratory parameters included serum creatinine which is being assessed from Baseline and 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. For the end of therapy (Week 104/4 week post last dose assessment), serum creatinine is being analyzed at both Weeks 100 and 104 (or last dose and 4 week post last dose visits for participants withdrawing early from study treatment), and the mean is being calculated. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Change from Baseline in serum creatinine levels at the indicated time points [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Clinical chemistry laboratory parameters included serum creatinine which is being assessed from Baseline and 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. For the end of therapy (Week 104/4 week post last dose assessment), serum creatinine is being analyzed at both Weeks 100 and 104 (or last dose and 4 week post last dose visits for participants withdrawing early from study treatment), and the mean is being calculated. The ratio is defined as the value at the defined time point divided by the Baseline value. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Serum albumin at the indicated time points [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Clinical chemistry laboratory parameters included serum albumin which is being assessed from Baseline and 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. For the end of therapy (Week 104/4 week post last dose assessment), serum albumin is being analyzed at both Weeks 100 and 104 (or last dose and 4 week post last dose visits for participants withdrawing early from study treatment), and the mean is being calculated. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Change from Baseline in levels of serum albumin at the indicated time points [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Clinical chemistry laboratory parameters included serum albumin which is being assessed from Baseline and 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. For the end of therapy (Week 104/4 week post last dose assessment), serum albumin is being analyzed at both Weeks 100 and 104 (or last dose and 4 week post last dose visits for participants withdrawing early from study treatment), and the mean is being calculated. The ratio is defined as the value at the defined time point divided by the Baseline value. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Cholesterol at the indicated time points [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Clinical chemistry laboratory parameters included cholesterol which is being assessed from Baseline and up to Week 128/6 month follow-up visit. Baseline for cholesterol is defined as the mean of the Screening and Day 0 values. For the end of therapy (Week 104/4 week post last dose assessment), cholesterol is being analyzed at both Weeks 100 and 104 (or last dose and 4 week post last dose visits for participants withdrawing early from study treatment), and the mean is being calculated. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Change from Baseline in levels of cholesterol at the indicated time points [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Clinical chemistry laboratory parameters included cholesterol which is being assessed from Baseline and up to Week 128/6 month follow-up visit. Baseline for cholesterol is defined as the mean of the Screening and Day 0 values. For the end of therapy (Week 104/4 week post last dose assessment), cholesterol is being analyzed at both Weeks 100 and 104 (or last dose and 4 week post last dose visits for participants withdrawing early from study treatment), and the mean is being calculated. The ratio is defined as the value at the defined time point divided by the Baseline value. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Summary of incidence of oedema by severity [ Time Frame: Screening and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Reduction of proteinuria lessens the risk of thromboembolic and cardiovascular effects and reduces the oedema in participants. Investigators are physically reviewing participants for clinical manifestations of idiopathic membranous glomerulonephropathy (IMGN) (e.g. oedema extending beyond calf) during study. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Change from Baseline in SF-36 v2 Quality of Life (QoL) questionnaire score [ Time Frame: From Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Health-related quality of life is being assessed through participant self-completion of the short form health survey (SF-36 version [v2]), a general health related quality of life metrics. The SF-36 v2 is referred to as a generic measure as it assesses health concepts that represent basic human values that are relevant to everyone's functional status and wellbeing. SF-36 is being administered prior to any procedures at Screening, Day 0, and Weeks 12, 28, 52, 76 and 104/4 week post last dose. For participants on 12 weekly follow-up, assessment of SF-36 is being conducted at the closest visit to those in the treatment phase. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • 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 ] [ Designated as safety issue: No ]
    The first occurrence of Cmax is being determined directly from the serum concentration-time data. The pharmacokinetic (PK) parameters are being calculated by standard non-compartmental analysis and all calculations of non-compartmental parameters are being based on actual sampling times. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Summary of minimum observed concentration (Cmin) of belimumab at the indicated time points [ Time Frame: Baseline and up to 4 week post last dose ] [ Designated as safety issue: No ]
    Trough concentration (Cmin) samples collected on the specified days are being used to assess attainment of steady state. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • 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 ] [ Designated as safety issue: No ]
    The AUC(0-2) is being determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples for PK analysis are being 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 for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Summary of total amount of urine excreted Ae(0-24) [ Time Frame: Baseline and up to 4 week post last dose ] [ Designated as safety issue: No ]
    PK parameters from the urine concentration data: urine Ae(0-24) is being assessed. 24 h urine collections for PK analysis are being collected after the Day 0 and Weeks 12, 28, 52, 76 doses and at the 4 week post last dose visit. A population approach will be 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 is being conducted using nonlinear mixed-effect modeling (NONMEM) or appropriate nonlinear mixed-effect analysis software. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Summary of clinical chemistry laboratory parameters assessed up to Week 116/16 week post last dose [ Time Frame: Baseline and up to Week 116/16 week follow-up visit ] [ Designated as safety issue: No ]
    Clinical chemistry laboratory parameters included blood urea nitrogen (BUN), potassium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and direct bilirubin, creatinine, chloride, uric acid, glucose, total carbondioxide (CO2), gamma glutamyltransferase (GGT), albumin, sodium, calcium, alkaline phosphatase, total protein, eGFR, cholesterol, inorganic phosphates, magnesium, immunoglobulin (Ig) G, IgA, IgM and lactate dehydrogenase assessed up to Week 128/6 month follow-up visit. IgG is being assessed at Screening, then each dosing visit up to Week 52 and Weeks 60, 68, 76, 84, 92, 100, Week 104/4 week post last dose and 16 week and 6 month follow-up visits. IgA and IgM is being assessed at Screening, and then at Week 0, 28 and at Week 104/4 week post last dose. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Summary of haematology laboratory parameters assessed up to Week 116/16 week post last dose [ Time Frame: Baseline and up to Week 116/16 week follow-up visit ] [ Designated as safety issue: No ]
    Hematology laboratory parameters included platelet count, red blood cells (RBC) count, white blood cell (WBC) count, haemoglobin, haematocrit, neutrophils, lymphocytes, monocytes, eosinophils and basophils assessed up to Week 128/6 month follow-up visit. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Summary of urinalysis parameters assessed up to Week 116/16 week post last dose [ Time Frame: Baseline and up to Week 116/16 week follow-up visit ] [ Designated as safety issue: No ]
    Urinalysis included pH, glucose, protein, blood and ketones by dipstick, microscopic examination and urine pregnancy assessed up to Week 128/6 month follow-up visit. Urinalysis is done pre-dose during dosing visits. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Vital signs measurements assessed up to 116/16 week follow-up visit [ Time Frame: Baseline and up to Week 116/16 week follow-up visit ] [ Designated as safety issue: No ]
    Vital signs including systolic and diastolic blood pressure, pulse rate and temperature were measured throughout the 104-week treatment period and follow-up. Sitting blood pressure/heart rate and body temperature are being measured pre-dose on dosing days. Blood pressure is being measured on at least 2 clinic visits during the Screening phase or by a 24 h ambulatory blood pressure monitor. Additionally, weight is being measured at all dosing visits prior to dosing and at Week 104. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Immunogenicity during the 104-week treatment period and up to Week 116/16 week follow-up visit [ Time Frame: Baseline and up to Week 116/16 week follow-up visit ] [ Designated as safety issue: No ]
    Immunogenicity samples are being collected pre-dose on Weeks 0, 12, 28, 40, 52, 76 and 4 week post last dose and the 16 week post last dose visit for belimumab immunogenicity assay. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Urine membrane attack complex (MAC) [ Time Frame: Baseline and up to 4 week post last dose ] [ Designated as safety issue: No ]
    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. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Change from Baseline in urine membrane attack complex (MAC) [ Time Frame: Baseline and up to 4 week post last dose ] [ Designated as safety issue: No ]
    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 adjut for urine dilution, before calculation of the ratio as value at time point divided by value at Baseline (Day 0). The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Change from Baseline in B Cell and T Cell subpopulations [ Time Frame: Baseline and up to Week 128/6 month post last dose ] [ Designated as safety issue: No ]
    Blood samples for flow cytometry quantification of peripheral lymphocyte (B cell and T cell) subpopulations and activation markers are being collected on Day 0 and at the Week 8, 16, 28, 4 week post last dose and 6 month post last dose visits. B cell Facs panels are being 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 are being 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. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Change from Baseline in cytokines/chemokines [ Time Frame: Baseline and up to Week 104/4 week post last dose ] [ Designated as safety issue: No ]
    Cytokine/chemokines associated with T helper skewing or autoimmune pathology will be analyzed using Luminex, ELISA. Serum analyte quantification is being used to confirm altered protein levels of any gene expression increases or decreases identified by transcriptomic analysis. Cytokine/chemokine samples are being collected on Day 0 and Weeks 8, 16, 28, 52, 76, and 4 week post last dose. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Serum BLys levels [ Time Frame: Baseline and Week 116/16 week follow-up visit ] [ Designated as safety issue: No ]
    Free BLyS protein is being analyzed using an ELISA. Serum samples are being collected before treatment and after belimumab washout at Week 0 and Week 116/16 week follow-up visit. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Urine BLys levels as a ratio to creatinine [ Time Frame: Baseline and Week 116/16 week follow-up visit ] [ Designated as safety issue: No ]
    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. The results for this outcome measure will be reported at the end of the study i.e. May 2017, as they were not designed to be reported at interim periods.
  • Change from baseline in proteinuria levels [ Time Frame: Weeks 12, 28, 52, 76 and 104 ] [ Designated as safety issue: No ]
  • Change from baseline in anti-PLA2R autoantibody titres [ Time Frame: Weeks 12, 28, 52, 76 and 104 ] [ Designated as safety issue: No ]
  • Change from baseline in urine levels of belimumab [ Time Frame: Weeks 12, 28, 52, 76 and 104 ] [ Designated as safety issue: No ]
  • Incidence of complete or partial remission [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
    Complete remission: PCR <30mg/mmol (proteinuria <0.3g/24h) with no worsening in renal function (estimated glomerular filtration rate (eGFR) reduction from baseline <15%). Partial remission: PCR <350mg/mmol (proteinuria <3.5g/24h) but ≥ 30mg/mmol (proteinuria ≥0.3g/24h) AND decrease of >50% from Day 0 baseline, together with no worsening in renal function (eGFR reduction from baseline <15%)
  • Time to complete or partial remission [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
    Duration of complete or partial remission
  • Incidence of anti-PLA2R autoantibody remission: [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
    Full response: Antibody undetectable, Partial response: Reduction in titres by 50%. Time to anti-PLA2R autoantibody remission
  • Incidence of anti-PLA2R autoantibody relapse (antibody detectable after previously undetectable) [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
  • Change from baseline in eGFR levels [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
  • Change from baseline in serum creatinine levels [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
  • Change from baseline in levels of serum albumin [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
  • Change from baseline in levels of cholesterol [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
  • Incidence of oedema (extending beyond calf) [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
  • Serum belimumab Cmax, Cmin, AUC(0-2), and urine Ae(0-24) [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
  • Change from baseline in SF-36 v2 Quality of Life (QoL) questionnaire score [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
    To evaluate the effect of belimumab on quality of life in IMGN
  • Pharmacodynamic/biomarker endpoints may include Urine membrane attack complex (MAC), B Cell and T Cell sub-populations, BLyS levels cytokines/chemokines antigen specific lymphocyte response, autoantibody profile, change in transcriptomic profile [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
    (may include but not limited to IL-21, IL-17, IL-4, IL-10,IFN-Gamma), or other markers of IMGN or autoimmune pathology, as data permits
  • Safety and tolerability [ Time Frame: 100 Weeks ] [ Designated as safety issue: No ]
    as assessed by evaluation of adverse events (AE), clinical laboratory assessments (clinical chemistry, haematology and urinalysis), vital signs and immunogenicity
Not Provided
Not Provided
 
A Study of Belimumab in Idiopathic Membranous Glomerulonephropathy
BEL116472. A 2 Year Mechanistic 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.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Glomerulonephritis, Membranous
Drug: belimumab
10mg/kg administered intravenously
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.
Intervention: Drug: belimumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
14
August 2016
September 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT01610492
116472
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP