Eculizumab in Primary MPGN (EAGLE)

January 15, 2018 updated by: Mario Negri Institute for Pharmacological Research

EVALUATING THE MORPHOFUNCTIONAL EFFECTS OF ECULIZUMAB THERAPY IN PRIMARY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS: A PILOT, SINGLE ARM STUDY IN TEN PATIENTS WITH PERSISTENT HEAVY PROTEINURIA

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bolzano, Italy, 39100
        • Ospedale Centrale
      • Napoli, Italy
        • Policlinico "Federico II" - U.O. Nefrologia
      • Rimini, Italy
        • Ospedale degli Infermi - U.O. Nefrologia e Dialisi
      • Roma, Italy
        • C.I. Columbus-Università Cattolica del S.Cuore - UOC Nefrologia e Dialisi
      • Roma, Italy
        • Ospedale Pediatrico "Bambin Gesù" - U.O. Nefrologia
      • Torino, Italy
        • Presidio Ospedaliero O.I.R.M. "Sant'Anna" - U.O. Nefrologia
      • Trento, Italy
        • Ospedale "Santa Chiara" - U.O. Nefrologia
      • Treviso, Italy
        • Ospedale Cà Foncello - U.O. Nefrologia
    • BA
      • Bari, BA, Italy
        • Ospedale Pediatrico "Giovanni XXIII" - U:O Nefrologia
    • BG
      • Bergamo, BG, 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
    • BO
      • Bologna, BO, Italy
        • Policlinico Sant'Orsola -Malpighi - U.O.S. Nefrologia e dialisi pediatrica
    • ME
      • Messina, ME, Italy
        • Policlinico "G.Martino" - U.O. Nefrologia e Dialisi
    • PD
      • Padova, PD, Italy
        • Policlinico Universitario di Padova - U.O. Nefrologia Pediatrica

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Soliris

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
24hours proteinuria
Time Frame: Changes from baseline at week 1,12,24,36,48 and 72.
Changes from baseline at week 1,12,24,36,48 and 72.

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
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.
Changes from Baseline at 1,24, 48 and 72 week.
Time to disease progression.
Time Frame: Up 72 week.
Up 72 week.

Other Outcome Measures

Outcome Measure
Time Frame
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
Participants will be followed for the duration of the study, an expected average of 72 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mario Negri Institute for Pharmacological Research

Collaborators

Alexion Pharma Italy s.r.l.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2014

Primary Completion (Actual)

December 1, 2017

Study Completion (Actual)

December 1, 2017

Study Registration Dates

First Submitted

March 17, 2014

First Submitted That Met QC Criteria

March 19, 2014

First Posted (Estimate)

March 21, 2014

Study Record Updates

Last Update Posted (Actual)

January 17, 2018

Last Update Submitted That Met QC Criteria

January 15, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EAGLE
  • 2013-003826-10 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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