ECULIZUMAB THERAPY IN PRIMARY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2013-003826-10-IT
• Date of registration: 28/10/2013
• Prospective Registration: Yes
• Primary sponsor: IRCCS- Mario Negri Institute
• Public title: ECULIZUMAB THERAPY IN PRIMARY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
• Scientific title: EVALUATING THE MORPHOFUNCTIONAL EFFECTS OF ECULIZUMAB THERAPY IN PRIMARY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS: A PILOT, SINGLE ARM STUDY IN TEN PATIENTS WITH PERSISTENT HEAVY PROTEINURIA - Eculizumab in primary MPGN
• Date of first enrolment: 24/01/2014
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003826-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: intra-patient; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy

Contacts

• Name: Lab. Regulatory Affairs for CT
• Affiliation: IRCCS - Mario Negri Institute

• Name: Lab. Regulatory Affairs for CT
• Affiliation: IRCCS - Mario Negri Institute

Key inclusion & exclusion 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)

Are the trial subjects under 18? yes
Number of subjects for this age range: 6
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 immunosoppressive 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Membranoproliferative glomerulonephritis

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: Soliris
Product Name: Soliris
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: ECULIZUMAB
CAS Number: 219685-50-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Main Objective: To evaluate whether Eculizumab therapy may reduce 24 hour proteinuria, considered as a continuous variable, at 6 months (week-24) and 12 months (week-48) compared to baseline

Primary end point(s): Reduction in 24 hour proteinuria, considered as a continuous variable

Secondary Objective: - To assess whether Eculizumab therapy may achieve persistent, either complete or partial, remission of the nephrotic syndrome.
- To assess the effect of Eculizumab therapy on relapses of nephrotic syndrome.
- To assess the effect of Eculizumab therapy on clinical and laboratory parameters and renal functional parameters
- To assess the effect of Eculizumab therapy on markers of complement activity (C3, C4, C3a, C5a, Bb and sC5b9) and immunohistochemical (C3, C5b-9, IgG, IgA, IgM, C4d, C1q, kappa light chain, lambda light chain, CD21, C5aR), structural and ultrastructural changes associated with remission of proteinuria in patients with evidence of complete or partial remission of the nephrotic syndrome- To assess the safety profile and the cost/effectiveness of the Eculizumab treatment-To evaluate biomarkers (see table) to be tested in case of significant treatment effect on the primary efficacy variable.

Timepoint(s) of evaluation of this end point: At basal and at 1,12,24,36,48 weeks.

Secondary Outcome(s)

Secondary end point(s): 1) Complete or partial remission of the nephrotic syndrome
2) Normalization (reduction to <303 ng/ml) of sC5b-9 plasma levels
Normalization in plasma levels of other components of the complement system including C3, C4, C3a, C5a, and Bb
3) Amelioration of kidney function/perfusion parameters including measured glomerular filtration rate (GFR); albumin, IgG, sodium and potassium fractional clearance; renal resistivity index

Timepoint(s) of evaluation of this end point: 1) Alla fine dello studio
2) Al basale e alle settimane 2,3,4,8,12,16,20,24,28,32,36,40,44 e 48.
3) Al basale e alle settimane 1, 24 e 48.

Secondary ID(s)

EAGLE

Source(s) of Monetary Support

Alexion Pharmaceuticals inc.

IRCCS - Mario Negri Institute

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 08/06/2019
• Date Completed: 24/05/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-003826-10/results