Clinical trial NCT02093533: Eculizumab in Primary MPGN
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Membranoproliferative Glomerulonephritis
Keywords: Membranoproliferative glomerulonephritis
Nephrotic syndrome
Proteinuria
Alternative complement pathway
Complement inhibition
Eculizumab
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
Collaborators: name: Alexion Pharma Italy s.r.l.
First posted: 2014-03-21
Enrollment: 10
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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)

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

Primary outcomes:
measure: 24hours proteinuria
timeFrame: Changes from baseline at week 1,12,24,36,48 and 72.
Secondary outcomes:
measure: Terminal complement complex (sC5b-9) levels
timeFrame: Changes from baseline at 1,2, 3, 4,12,24,36,48,52,56,60 and 72 week.
measure: Glomerular filtration rate (GFR) measured by iohexol plasma clearance and estimated.
timeFrame: Changes from Baseline at 1,24, 48 and 72 week.
measure: Time to disease progression.
timeFrame: Up 72 week.
Other outcomes:
measure: Number of participants with Adverse Events as a measure of safety.
timeFrame: Participants will be followed for the duration of the study, an expected average of 72 weeks
Locations:
city: Bari
country: Italy
facility: Ospedale Pediatrico "Giovanni XXIII" - U:O Nefrologia
state: BA
city: Bergamo
country: Italy
facility: A.O. Papa Giovanni XXIII - U.O. Nefrologia e Dialisi/IRCCS IRFMN - Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò
state: BG
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola -Malpighi - U.O.S. Nefrologia e dialisi pediatrica
state: BO
city: Messina
country: Italy
facility: Policlinico "G.Martino" - U.O. Nefrologia e Dialisi
state: ME
city: Padova
country: Italy
facility: Policlinico Universitario di Padova - U.O. Nefrologia Pediatrica
state: PD
city: Bolzano
country: Italy
facility: Ospedale Centrale
city: Napoli
country: Italy
facility: Policlinico "Federico II" - U.O. Nefrologia
city: Rimini
country: Italy
facility: Ospedale degli Infermi - U.O. Nefrologia e Dialisi
city: Roma
country: Italy
facility: C.I. Columbus-Università Cattolica del S.Cuore - UOC Nefrologia e Dialisi
city: Roma
country: Italy
facility: Ospedale Pediatrico "Bambin Gesù" - U.O. Nefrologia
city: Torino
country: Italy
facility: Presidio Ospedaliero O.I.R.M. "Sant'Anna" - U.O. Nefrologia
city: Trento
country: Italy
facility: Ospedale "Santa Chiara" - U.O. Nefrologia
city: Treviso
country: Italy
facility: Ospedale Cà Foncello - U.O. Nefrologia
Study officials:
References: