Overview

This trial is active, not recruiting.

Condition membranoproliferative glomerulonephritis
Treatment eculizumab
Phase phase 2
Target C5
Sponsor Mario Negri Institute for Pharmacological Research
Collaborator Alexion Pharma Italy s.r.l.
Start date March 2014
End date March 2017
Trial size 10 participants
Trial identifier NCT02093533, 2013-003826-10, EAGLE

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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
eculizumab Soliris

Primary Outcomes

Measure
24hours proteinuria
time frame: Changes from baseline at week 1,12,24,36,48 and 72.

Secondary Outcomes

Measure
Terminal complement complex (sC5b-9) levels
time frame: 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.
time frame: Changes from Baseline at 1,24, 48 and 72 week.
Time to disease progression.
time frame: Up 72 week.

Eligibility Criteria

Male or female participants up to 75 years old.

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

Additional Information

Official title EVALUATING THE MORPHOFUNCTIONAL EFFECTS OF ECULIZUMAB THERAPY IN PRIMARY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS: A PILOT, SINGLE ARM STUDY IN TEN PATIENTS WITH PERSISTENT HEAVY PROTEINURIA
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Mario Negri Institute for Pharmacological Research.