Eculizumab in Primary MPGN

Membranoproliferative Glomerulonephritis Clinical Trial

— EAGLE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02093533
• Other study ID #: EAGLE
• Secondary ID: 2013-003826-10
• Status: Completed
• Phase: Phase 2
• First received: March 17, 2014
• Last updated: January 15, 2018
• Start date: March 2014
• Est. completion date: December 2017

Study information

• Verified date: January 2018
• Source: Mario Negri Institute for Pharmacological Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Glomerulonephritis
• Glomerulonephritis, Membranoproliferative
• Membranoproliferative Glomerulonephritis

Intervention

Drug:
• Eculizumab

Locations

Country	Name	City	State
Italy	Ospedale Pediatrico "Giovanni XXIII" - U:O Nefrologia	Bari	BA
Italy	A.O. Papa Giovanni XXIII - U.O. Nefrologia e Dialisi/IRCCS IRFMN - Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò	Bergamo	BG
Italy	Policlinico Sant'Orsola -Malpighi - U.O.S. Nefrologia e dialisi pediatrica	Bologna	BO
Italy	Ospedale Centrale	Bolzano
Italy	Policlinico "G.Martino" - U.O. Nefrologia e Dialisi	Messina	ME
Italy	Policlinico "Federico II" - U.O. Nefrologia	Napoli
Italy	Policlinico Universitario di Padova - U.O. Nefrologia Pediatrica	Padova	PD
Italy	Ospedale degli Infermi - U.O. Nefrologia e Dialisi	Rimini
Italy	C.I. Columbus-Università Cattolica del S.Cuore - UOC Nefrologia e Dialisi	Roma
Italy	Ospedale Pediatrico "Bambin Gesù" - U.O. Nefrologia	Roma
Italy	Presidio Ospedaliero O.I.R.M. "Sant'Anna" - U.O. Nefrologia	Torino
Italy	Ospedale "Santa Chiara" - U.O. Nefrologia	Trento
Italy	Ospedale Cà Foncello - U.O. Nefrologia	Treviso

Sponsors (2)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research	Alexion Pharma Italy s.r.l.

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	24hours proteinuria		Changes from baseline at week 1,12,24,36,48 and 72.
Secondary	Terminal complement complex (sC5b-9) levels		Changes from baseline at 1,2, 3, 4,12,24,36,48,52,56,60 and 72 week.
Secondary	Glomerular filtration rate (GFR) measured by iohexol plasma clearance and estimated.		Changes from Baseline at 1,24, 48 and 72 week.
Secondary	Time to disease progression.		Up 72 week.