Membranoproliferative glomerulonephritis
Conditions
Interventions
Trade Name: Soliris
Product Name: Soliris
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: ECULIZUMAB
Sponsors
IRCCS- Mario Negri Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Biopsy-proven primary MPGN - Creatinine clearance >20 ml/min per 1.73m2 - 24-hour proteinuria persistently exceeding 3,5g in adults or exceeding 40mg/h/m2 in children (or exceeding 2mg protein/mg creatinine in children spot urine samples) - Persistently low C3 levels in at least two consecutive evaluations - Persistently high sC5b9 levels (>1000 ng/ml) in at least two previous consecutive evaluations - Written informed consent (by parents or tutors if underage) Are the trial subjects under 18? yes Number of subjects for this age range: 6 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 4 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Age > 75 years - Secondary MPGN (evidence of infection, immunological disease including vasculitis, systemic diseases and proliferative disorders) - Evidence at kidney biopsy evaluation of severe chronic histological changes that very unlikely could benefit of eculizumab therapy - Concomitant steroid or immunosoppressive therapy for immuno-mediated disease - Pregnancy or lactating - Childbearing potential without effective contraception - Any clinically relevant condition that might affect completion of the study participation and/or confound study results - Inability to understand the potential risks and benefits of the study - Legal incapacity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate whether Eculizumab therapy may reduce 24 hour proteinuria, considered as a continuous variable, at 6 months (week-24) and 12 months (week-48) compared to baseline ; Secondary Objective: - To assess whether Eculizumab therapy may achieve persistent, either complete or partial, remission of the nephrotic syndrome. - To assess the effect of Eculizumab therapy on relapses of nephrotic syndrome. - To assess the effect of Eculizumab therapy on clinical and laboratory parameters and renal functional parameters - To assess the effect of Eculizumab therapy on markers of complement activity (C3, C4, C3a, C5a, Bb and sC5b9) and immunohistochemical (C3, C5b-9, IgG, IgA, IgM, C4d, C1q, kappa light chain, lambda light chain, CD21, C5aR), structural and ultrastructural changes associated with remission of proteinuria in patients with evidence of complete or partial remission of the nephrotic syndrome- To assess the safety profile and the cost/effectiveness of the Eculizumab treatment-To evaluate biomarkers (see table) to be tested in case of significant treatment effect on the primary efficacy variable. ;Primary end point(s): Reduction in 24 hour proteinuria, considered as a continuous variable ;Timepoint(s) of evaluation of this end point: At basal and at 1,12,24,36,48 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Complete or partial remission of the nephrotic syndrome 2) Normalization (reduction to <303 ng/ml) of sC5b-9 plasma levels Normalization in plasma levels of other components of the complement system including C3, C4, C3a, C5a, and Bb 3) Amelioration of kidney function/perfusion parameters including measured glomerular filtration rate (GFR); albumin, IgG, sodium and potassium fractional clearance; renal resistivity index ; Timepoint(s) of evaluation of this end point: 1) Alla fine dello studio 2) Al basale e alle settimane 2,3,4,8,12,16,20,24,28,32,36,40,44 e 48. 3) Al basale e alle settimane 1, 24 e 48. | — |
Countries
Italy
Contacts
Public ContactLab. Regulatory Affairs for CT
IRCCS - Mario Negri Institute
Outcome results
None listed