Conditions: Glomerulonephritis, Membranous
Keywords: IMGN anti-PLA2R antibodies pharmacokinetics belimumab Benlysta Idiopathic Membranous Glomerulonephropathy safety GSK1550188 Lymphostat-B membrane attack complex
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 14
Healthy volunteers: no

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

Detailed description:

Arms:
arm 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.

Interventions: intervention 1: belimumab
Intervention descriptions: intervention 1: 10mg/kg administered intravenously

Protocol document: