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NCT01610492

A Study of Belimumab in Idiopathic Membranous Glomerulonephropathy

Completed Phase 2 Results posted Last updated 13 October 2017
What this trial tests

Phase 2 trial testing belimumab in Glomerulonephritis, Membranous in 14 participants. Completed in 14 September 2016.

Timeline
1 July 2012
Primary endpoint
24 September 2014
14 September 2016

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment14
Start date1 July 2012
Primary completion24 September 2014
Estimated completion14 September 2016
Sites8 locations across United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 75, any sex, with Glomerulonephritis, Membranous. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Proteinuria Levels at Week 28 Primary · 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 e

GroupValue95% CI
Belimumab 10 mg/kg IV0.7552± 45.0
Change From Baseline in Anti-phospholipase A2 Receptor (PLA2R) Autoantibody Titers at Week 28 Primary · 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.

GroupValue95% CI
Belimumab 10 mg/kg IV0.2666± 171.0
Proteinuria Levels at the Indicated Time Points Secondary · 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).

Baseline, n=14
GroupValue95% CI
Belimumab 10 mg/kg IV724.3157± 40.2
Week 12, n=13
GroupValue95% CI
Belimumab 10 mg/kg IV670.8655± 46.9
Week 28, n=11
GroupValue95% CI
Belimumab 10 mg/kg IV498.1255± 40.9
Week 52, n=9
GroupValue95% CI
Belimumab 10 mg/kg IV356.4209± 174.8
Week 76, n=8
GroupValue95% CI
Belimumab 10 mg/kg IV274.9714± 70.4
Week 104, n=10
GroupValue95% CI
Belimumab 10 mg/kg IV129.9761± 186.0
Week 128, n=9
GroupValue95% CI
Belimumab 10 mg/kg IV75.2359± 136.4
Change From Baseline in Proteinuria Levels at the Indicated Time Points Secondary · 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 th

Week 12; n= 13
GroupValue95% CI
Belimumab 10 mg/kg IV0.9437± 39.3
Week 28; n= 11
GroupValue95% CI
Belimumab 10 mg/kg IV0.7552± 45.0
Week 52; n= 9
GroupValue95% CI
Belimumab 10 mg/kg IV0.5297± 206.7
Week 76; n= 8
GroupValue95% CI
Belimumab 10 mg/kg IV0.4177± 54.3
Week 104; n= 10
GroupValue95% CI
Belimumab 10 mg/kg IV0.1874± 189.3
Week 128; n= 9
GroupValue95% CI
Belimumab 10 mg/kg IV0.1118± 139.1
Anti-phospholipase A2 Receptor (PLA2R) Autoantibody Levels at Indicated Time Points Secondary · 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).

Baseline, n=14
GroupValue95% CI
Belimumab 10 mg/kg IV168.3± 138.9
Week 12, n=13
GroupValue95% CI
Belimumab 10 mg/kg IV91.0± 200.4
Week 28, n=11
GroupValue95% CI
Belimumab 10 mg/kg IV46.4± 319.6
Week 52, n=9
GroupValue95% CI
Belimumab 10 mg/kg IV12.9± 358.4
Week 76, n=8
GroupValue95% CI
Belimumab 10 mg/kg IV7.5± 140.4
Week 104, n=10
GroupValue95% CI
Belimumab 10 mg/kg IV3.7± 72.7
Week 128, n=8
GroupValue95% CI
Belimumab 10 mg/kg IV4.4± 112.0
Change From Baseline in Anti-PLA2R Autoantibody Titers at the Indicated Time Points Secondary · 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).

Week 12; n= 13
GroupValue95% CI
Belimumab 10 mg/kg IV0.5362± 58.1
Week 28; n= 11
GroupValue95% CI
Belimumab 10 mg/kg IV0.2666± 171.0
Week 52; n= 9
GroupValue95% CI
Belimumab 10 mg/kg IV0.0737± 130.3
Week 76; n= 8
GroupValue95% CI
Belimumab 10 mg/kg IV0.0436± 102.8
Week 104; n= 10
GroupValue95% CI
Belimumab 10 mg/kg IV0.0212± 169.1
Week 128; n= 8
GroupValue95% CI
Belimumab 10 mg/kg IV0.0284± 243.7
Number of Participants With Complete or Partial Remission Secondary · 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).

Week 12; Partial remission; n= 13
GroupValue95% CI
Belimumab 10 mg/kg IV0
Week 12; Complete remission; n= 13
GroupValue95% CI
Belimumab 10 mg/kg IV0
Week 28; Partial remission; n= 11
GroupValue95% CI
Belimumab 10 mg/kg IV1
Week 28; Complete remission; n= 11
GroupValue95% CI
Belimumab 10 mg/kg IV0
Week 52; Partial remission; n= 9
GroupValue95% CI
Belimumab 10 mg/kg IV2
Week 52; Complete remission; n= 9
GroupValue95% CI
Belimumab 10 mg/kg IV1
Week 76; Partial remission; n= 8
GroupValue95% CI
Belimumab 10 mg/kg IV3
Week 76; Complete remission; n= 8
GroupValue95% CI
Belimumab 10 mg/kg IV0
Time to Complete or Partial Remission Secondary · 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 comple

GroupValue95% CI
Belimumab 10 mg/kg IV68.2028.00 – 93.60
Duration of Complete or Partial Remission Secondary · 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 participa

Complete remission; n= 1
GroupValue95% CI
Belimumab 10 mg/kg IV365.0± NA
Partial remission; n= 9
GroupValue95% CI
Belimumab 10 mg/kg IV378.6± 186.15
Number of Participants With PLA2R Autoantibody Remission Secondary · 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).

Week 12; full response; n= 13
GroupValue95% CI
Belimumab 10 mg/kg IV1
Week 12; partial response; n= 13
GroupValue95% CI
Belimumab 10 mg/kg IV3
Week 28; full response; n= 11
GroupValue95% CI
Belimumab 10 mg/kg IV3
Week 28; partial response; n= 11
GroupValue95% CI
Belimumab 10 mg/kg IV6
Week 52; full response; n= 9
GroupValue95% CI
Belimumab 10 mg/kg IV4
Week 52; partial response; n= 9
GroupValue95% CI
Belimumab 10 mg/kg IV5
Week 76; full response; n= 8
GroupValue95% CI
Belimumab 10 mg/kg IV4
Week 76; partial response; n= 8
GroupValue95% CI
Belimumab 10 mg/kg IV4
Time to Anti-PLA2R Autoantibody Remission Secondary · 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.

Partial response
GroupValue95% CI
Belimumab 10 mg/kg IV16.208.00 – 24.00
Complete response
GroupValue95% CI
Belimumab 10 mg/kg IV82.0016.00 – 92.00
Number of Participants With Anti-PLA2R Autoantibody Relapse Secondary · 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).

Week 12; n= 13
GroupValue95% CI
Belimumab 10 mg/kg IV0
Week 28; n= 11
GroupValue95% CI
Belimumab 10 mg/kg IV0
Week 52; n= 9
GroupValue95% CI
Belimumab 10 mg/kg IV0
Week 76; n= 8
GroupValue95% CI
Belimumab 10 mg/kg IV0
Week 104; n= 10
GroupValue95% CI
Belimumab 10 mg/kg IV0
Week 128; n= 8
GroupValue95% CI
Belimumab 10 mg/kg IV0

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Belimumab 10 mg/kg IV
Serious: 3/14 (21%)
Deaths:

Serious adverse events (3 terms)

ReactionSystemBelimumab 10 mg/kg IV
CellulitisInfections and infestations
Weight decreasedInvestigations
EmbolismVascular disorders
Other adverse events (71 terms — click to expand)

ReactionSystemBelimumab 10 mg/kg IV
Upper respiratory tract infectionInfections and infestations
Viral upper respiratory tract infectionInfections and infestations
Muscle spasmsMusculoskeletal and connective tissue disorders
Lower respiratory tract infectionInfections and infestations
RhinitisInfections and infestations
DiarrhoeaGastrointestinal disorders
DyspepsiaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
DizzinessNervous system disorders
RashSkin and subcutaneous tissue disorders
Skin lesionSkin and subcutaneous tissue disorders
Chest painGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Viral infectionInfections and infestations
Rectal haemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
CellulitisInfections and infestations
Oral candidiasisInfections and infestations
Respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
AscitesGastrointestinal disorders
Irritable bowel syndromeGastrointestinal disorders
NauseaGastrointestinal disorders
Flank painMusculoskeletal and connective tissue disorders
Joint swellingMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
MigraineNervous system disorders
PresyncopeNervous system disorders
Rash pruriticSkin and subcutaneous tissue disorders
Swelling faceSkin and subcutaneous tissue disorders
MalaiseGeneral disorders
PyrexiaGeneral disorders
TinnitusEar and labyrinth disorders

Most-reported serious reactions: Cellulitis, Weight decreased, Embolism.

Data from ClinicalTrials.gov NCT01610492 adverse events section.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity.
    Vincent FB, Saulep-Easton D, Figgett WA, Fairfax KA, et al · · 2013 · cited 333× · PMID 23684423 · DOI 10.1016/j.cytogfr.2013.04.003
  2. B Cells, Antibodies, and More.
    Hoffman W, Lakkis FG, Chalasani G. · · 2016 · cited 332× · PMID 26700440 · DOI 10.2215/cjn.09430915
  3. B-cell targeted therapeutics in clinical development.
    Blüml S, McKeever K, Ettinger R, Smolen J, et al · · 2013 · cited 74× · PMID 23566679 · DOI 10.1186/ar3906
  4. Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational Perspectives.
    Schrezenmeier E, Jayne D, Jayne D, Dörner T. · · 2018 · cited 47× · PMID 29326157 · DOI 10.1681/asn.2017040367
  5. Effectiveness, Tolerability, and Safety of Belimumab in Patients with Refractory SLE: a Review of Observational Clinical-Practice-Based Studies.
    Trentin F, Gatto M, Zen M, Larosa, et al · · 2018 · cited 29× · PMID 29512034 · DOI 10.1007/s12016-018-8675-2
  6. Future landscape for the management of membranous nephropathy.
    Caravaca-Fontán F, Yandian F, Fervenza FC. · · 2023 · cited 21× · PMID 37529655 · DOI 10.1093/ckj/sfad041
  7. A narrative review of potential drug treatments for nephritis in children with IgA vasculitis (HSP).
    Williams CEC, Lamond M, Marro J, Chetwynd AJ, et al · · 2023 · cited 17× · PMID 37755547 · DOI 10.1007/s10067-023-06781-8

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