Eculizumab in Primary MPGN (EAGLE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Mario Negri Institute for Pharmacological Research
Sponsor:
Collaborator:
Alexion Pharma Italy s.r.l.
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:
NCT02093533
First received: March 17, 2014
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Membranoproliferative Glomerulonephritis
Drug: Eculizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Mario Negri Institute for Pharmacological Research:

Primary Outcome Measures:
  • 24hours proteinuria [ Time Frame: Changes from baseline at week 1,12,24,36,48 and 72. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • Glomerular filtration rate (GFR) measured by iohexol plasma clearance and estimated. [ Time Frame: Changes from Baseline at 1,24, 48 and 72 week. ] [ Designated as safety issue: No ]
  • Time to disease progression. [ Time Frame: Up 72 week. ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10
Study Start Date: March 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eculizumab
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
Other Name: Soliris

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02093533

Contacts
Contact: Piero Ruggenenti, MD piero.ruggenenti@marionegri.it

Locations
Italy
Ospedale Pediatrico "Giovanni XXIII" - U:O Nefrologia Terminated
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 Recruiting
Bergamo, BG, Italy
Contact: Giuseppe Remuzzi, MD       gremuzzi@hpg23.it   
Principal Investigator: Piero Ruggenenti, MD         
Sub-Investigator: Elena Mondo, MD         
Policlinico Sant'Orsola -Malpighi - U.O.S. Nefrologia e dialisi pediatrica Recruiting
Bologna, BO, Italy
Contact: Giovanni Montini, MD       giovanni.montini@aosp.bo.it   
Principal Investigator: Giovanni Montini, MD         
Policlinico "G.Martino" - U.O. Nefrologia e Dialisi Recruiting
Messina, ME, Italy
Contact: Domenico Santoro, MD       dsantoro@unime.it   
Principal Investigator: Domenico Santoro, MD         
Policlinico Universitario di Padova - U.O. Nefrologia Pediatrica Not yet recruiting
Padova, PD, Italy
Contact: Luisa Murer, MD       murer@pediatria.unipd.it   
Principal Investigator: Luisa Murer, MD         
Sub-Investigator: Elisabetta Benetti, MD         
Ospedale Centrale Recruiting
Bolzano, Italy, 39100
Contact: Bruno Giacon, MD       bruno.giacon@asbz.it   
Principal Investigator: Bruno Giacon, MD         
Policlinico "Federico II" - U.O. Nefrologia Recruiting
Napoli, Italy
Contact: Antonio Pisani, MD       antonio.pisani@libero.it   
Principal Investigator: Antonio Pisani, MD         
Ospedale Pediatrico "Bambin Gesù" - U.O. Nefrologia Recruiting
Roma, Italy
Contact: Francesco Emma, MD       emma@opbg.net   
Principal Investigator: Francesco Emma, MD         
Sub-Investigator: Marina Vivarelli, MD         
C.I. Columbus-Università Cattolica del S.Cuore - UOC Nefrologia e Dialisi Not yet recruiting
Roma, Italy
Contact: Stefano Passalacqua, MD       passalacqua@aferesi.it   
Principal Investigator: Stefano Passalacqua, MD         
Presidio Ospedaliero O.I.R.M. "Sant'Anna" - U.O. Nefrologia Not yet recruiting
Torino, Italy
Contact: Rosanna Coppo, MD         
Principal Investigator: Rosanna Coppo, MD         
Sub-Investigator: Alessandro Amore, MD         
Ospedale "Santa Chiara" - U.O. Nefrologia Terminated
Trento, Italy
Ospedale Cà Foncello - U.O. Nefrologia Recruiting
Treviso, Italy
Contact: Alessandra Pasi, Md       apasi@ulss.tv.it   
Principal Investigator: Alessandra Pasi, MD         
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Alexion Pharma Italy s.r.l.
  More Information

No publications provided

Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT02093533     History of Changes
Other Study ID Numbers: EAGLE, 2013-003826-10
Study First Received: March 17, 2014
Last Updated: September 24, 2014
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Mario Negri Institute for Pharmacological Research:
Membranoproliferative glomerulonephritis
Nephrotic syndrome
Proteinuria
Alternative complement pathway
Complement inhibition
Eculizumab

Additional relevant MeSH terms:
Glomerulonephritis
Glomerulonephritis, Membranoproliferative
Nephritis
Kidney Diseases
Urologic Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on October 19, 2014