Membranoproliferative Glomerulonephritis
Conditions
Keywords
Membranoproliferative glomerulonephritis, Nephrotic syndrome, Proteinuria, Alternative complement pathway, Complement inhibition, Eculizumab
Brief summary
Membranoproliferative glomerulonephritis (MPGN) is the third or fourth leading cause of end stage renal disease among the primary glomerulonephritis. Hyperactivation of the alternative complement pathway and familial forms for all types of MPGN have been reported suggesting that genetic abnormalities may play a predisposing role to the disease. In recent case reports Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex ,is a safe and effective therapy.
Interventions
DRUGEculizumab
Sponsors
Alexion Pharma Italy s.r.l.
Mario Negri Institute for Pharmacological Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 75 Years
Healthy volunteers
No
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)
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 immunosuppressive 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 |
|---|---|
| 24hours proteinuria | Changes from baseline at week 1,12,24,36,48 and 72. |
Secondary
| Measure | Time frame |
|---|---|
| Terminal complement complex (sC5b-9) levels | Changes from baseline at 1,2, 3, 4,12,24,36,48,52,56,60 and 72 week. |
| Glomerular filtration rate (GFR) measured by iohexol plasma clearance and estimated. | Changes from Baseline at 1,24, 48 and 72 week. |
| Time to disease progression. | Up 72 week. |
Other
| Measure | Time frame |
|---|---|
| Number of participants with Adverse Events as a measure of safety. | Participants will be followed for the duration of the study, an expected average of 72 weeks |
Countries
Italy
Outcome results
None listed