Eculizumab in Primary MPGN (EAGLE)
Primary Purpose
Membranoproliferative Glomerulonephritis
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Eculizumab
Sponsored by
About this trial
This is an interventional treatment trial for Membranoproliferative Glomerulonephritis focused on measuring Membranoproliferative glomerulonephritis, Nephrotic syndrome, Proteinuria, Alternative complement pathway, Complement inhibition, Eculizumab
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
Sites / Locations
- Ospedale Pediatrico "Giovanni XXIII" - U:O Nefrologia
- A.O. Papa Giovanni XXIII - U.O. Nefrologia e Dialisi/IRCCS IRFMN - Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò
- Policlinico Sant'Orsola -Malpighi - U.O.S. Nefrologia e dialisi pediatrica
- Policlinico "G.Martino" - U.O. Nefrologia e Dialisi
- Policlinico Universitario di Padova - U.O. Nefrologia Pediatrica
- Ospedale Centrale
- Policlinico "Federico II" - U.O. Nefrologia
- Ospedale degli Infermi - U.O. Nefrologia e Dialisi
- C.I. Columbus-Università Cattolica del S.Cuore - UOC Nefrologia e Dialisi
- Ospedale Pediatrico "Bambin Gesù" - U.O. Nefrologia
- Presidio Ospedaliero O.I.R.M. "Sant'Anna" - U.O. Nefrologia
- Ospedale "Santa Chiara" - U.O. Nefrologia
- Ospedale Cà Foncello - U.O. Nefrologia
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Eculizumab
Arm Description
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
Outcomes
Primary Outcome Measures
24hours proteinuria
Secondary Outcome Measures
Terminal complement complex (sC5b-9) levels
Glomerular filtration rate (GFR) measured by iohexol plasma clearance and estimated.
Time to disease progression.
Full Information
NCT ID
NCT02093533
First Posted
March 17, 2014
Last Updated
January 15, 2018
Sponsor
Mario Negri Institute for Pharmacological Research
Collaborators
Alexion Pharma Italy s.r.l.
1. Study Identification
Unique Protocol Identification Number
NCT02093533
Brief Title
Eculizumab in Primary MPGN
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
March 2014 (Actual)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
December 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mario Negri Institute for Pharmacological Research
Collaborators
Alexion Pharma Italy s.r.l.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Membranoproliferative Glomerulonephritis
Keywords
Membranoproliferative glomerulonephritis, Nephrotic syndrome, Proteinuria, Alternative complement pathway, Complement inhibition, Eculizumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Eculizumab
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Eculizumab
Other Intervention Name(s)
Soliris
Primary Outcome Measure Information:
Title
24hours proteinuria
Time Frame
Changes from baseline at week 1,12,24,36,48 and 72.
Secondary Outcome Measure Information:
Title
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.
Title
Glomerular filtration rate (GFR) measured by iohexol plasma clearance and estimated.
Time Frame
Changes from Baseline at 1,24, 48 and 72 week.
Title
Time to disease progression.
Time Frame
Up 72 week.
Other Pre-specified Outcome Measures:
Title
Number of participants with Adverse Events as a measure of safety.
Time Frame
Participants will be followed for the duration of the study, an expected average of 72 weeks
10. Eligibility
Sex
All
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Ospedale Pediatrico "Giovanni XXIII" - U:O Nefrologia
City
Bari
State/Province
BA
Country
Italy
Facility Name
A.O. Papa Giovanni XXIII - U.O. Nefrologia e Dialisi/IRCCS IRFMN - Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò
City
Bergamo
State/Province
BG
Country
Italy
Facility Name
Policlinico Sant'Orsola -Malpighi - U.O.S. Nefrologia e dialisi pediatrica
City
Bologna
State/Province
BO
Country
Italy
Facility Name
Policlinico "G.Martino" - U.O. Nefrologia e Dialisi
City
Messina
State/Province
ME
Country
Italy
Facility Name
Policlinico Universitario di Padova - U.O. Nefrologia Pediatrica
City
Padova
State/Province
PD
Country
Italy
Facility Name
Ospedale Centrale
City
Bolzano
ZIP/Postal Code
39100
Country
Italy
Facility Name
Policlinico "Federico II" - U.O. Nefrologia
City
Napoli
Country
Italy
Facility Name
Ospedale degli Infermi - U.O. Nefrologia e Dialisi
City
Rimini
Country
Italy
Facility Name
C.I. Columbus-Università Cattolica del S.Cuore - UOC Nefrologia e Dialisi
City
Roma
Country
Italy
Facility Name
Ospedale Pediatrico "Bambin Gesù" - U.O. Nefrologia
City
Roma
Country
Italy
Facility Name
Presidio Ospedaliero O.I.R.M. "Sant'Anna" - U.O. Nefrologia
City
Torino
Country
Italy
Facility Name
Ospedale "Santa Chiara" - U.O. Nefrologia
City
Trento
Country
Italy
Facility Name
Ospedale Cà Foncello - U.O. Nefrologia
City
Treviso
Country
Italy
12. IPD Sharing Statement
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Eculizumab in Primary MPGN
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