Eculizumab in Primary MPGN

NCT02093533 | Completed Phase 2

• 2 other identifiers: EAGLE2013-003826-10
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 13

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.

Conditions

Membranoproliferative Glomerulonephritis

Keywords

Membranoproliferative glomerulonephritis; Nephrotic syndrome; Proteinuria; Alternative complement pathway; Complement inhibition; Eculizumab

Outcome Measures

Primary Outcomes (1)

• 24hours proteinuria

  Changes from baseline at week 1,12,24,36,48 and 72.

Secondary Outcomes (3)

• Terminal complement complex (sC5b-9) levels

  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.

  Changes from Baseline at 1,24, 48 and 72 week.

• Time to disease progression.

  Up 72 week.

Other Outcomes (1)

• 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

Study Arms (1)

Eculizumab

EXPERIMENTAL

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

Interventions

Eculizumab DRUG

Also known as: Soliris

Eculizumab

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy-proven primary MPGN
• Creatinine clearance \>20 ml/min per 1.73m2
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Alexion Pharma Italy s.r.l.: collaborator

Study Sites (13)

Ospedale Pediatrico "Giovanni XXIII" - U:O Nefrologia

Bari, BA, Italy

Location

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

Location

Policlinico Sant'Orsola -Malpighi - U.O.S. Nefrologia e dialisi pediatrica

Bologna, BO, Italy

Location

Policlinico "G.Martino" - U.O. Nefrologia e Dialisi

Messina, ME, Italy

Location

Policlinico Universitario di Padova - U.O. Nefrologia Pediatrica

Padua, PD, Italy

Location

Ospedale Centrale

Bolzano, 39100, Italy

Location

Policlinico "Federico II" - U.O. Nefrologia

Napoli, Italy

Location

Ospedale degli Infermi - U.O. Nefrologia e Dialisi

Rimini, Italy

Location

C.I. Columbus-Università Cattolica del S.Cuore - UOC Nefrologia e Dialisi

Roma, Italy

Location

Ospedale Pediatrico "Bambin Gesù" - U.O. Nefrologia

Roma, Italy

Location

Presidio Ospedaliero O.I.R.M. "Sant'Anna" - U.O. Nefrologia

Torino, Italy

Location

Ospedale "Santa Chiara" - U.O. Nefrologia

Trento, Italy

Location

Ospedale Cà Foncello - U.O. Nefrologia

Treviso, Italy

Location

MeSH Terms

Conditions

Glomerulonephritis, Membranoproliferative; Nephrotic Syndrome; Proteinuria

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Immune System Diseases; Nephrosis; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2014
• First Posted: March 21, 2014
• Study Start: March 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: January 17, 2018

Record last verified: 2018-01

Locations

IT (13)