Eculizumab in Primary MPGN

Study Overview
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Brief Summary
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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.

Official Title
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EVALUATING THE MORPHOFUNCTIONAL EFFECTS OF ECULIZUMAB THERAPY IN PRIMARY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS: A PILOT, SINGLE ARM STUDY IN TEN PATIENTS WITH PERSISTENT HEAVY PROTEINURIA

Conditions
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Membranoproliferative Glomerulonephritis

Intervention / Treatment
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* Drug: Eculizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eculizumab<br>Patient Body weight ≥40 kg: initial phase 900 mg weekly x 4 and maintenance phase 1200 mg at week 5; then 1200 mg every 2 weeks Patient Body weight 30 - <40 kg : initial phase 600 mg weekly x 2 and maintenance phase 900 mg at week 3; then 900 mg every 2 weeks | Drug: Eculizumab<br> <br> * Other names: Soliris;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24hours proteinuria |  | Changes from baseline at week 1,12,24,36,48 and 72. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nephrotic syndrome, Proteinuria, Alternative complement pathway, Complement inhibition, Eculizumab, Membranoproliferative glomerulonephritis