"A Randomized Controlled Trial of Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (IMN)"

• Register: EUCTR
• Last refreshed on: 31 July 2012
• Main ID: EUCTR2011-006115-59-IT
• Date of registration: 08/06/2012
• Prospective Registration: Yes
• Primary sponsor: AZIENDA OSPEDALIERA SPEDALI CIVILI DI BRESCIA
• Public title: "A Randomized Controlled Trial of Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (IMN)"
• Scientific title: "A Randomized Controlled Trial of Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (IMN)" - GNM-2011
• Date of first enrolment: 11/06/2012
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-006115-59
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Italy

Contacts

• Name: coordinamento ricerca clinica
• Affiliation: AO Spedali Civili di Brescia

• Name: coordinamento ricerca clinica
• Affiliation: AO Spedali Civili di Brescia

Key inclusion & exclusion criteria

Inclusion criteria:
1. Biopsy diagnosis of idiopathic MN, performed in the last 24 months
2. Proteinuria> 3.5 g/24h in three measurements (one measurement for 3 weeks)
3. Estimated GFR (MDRD formula) = 50ml/min/1.73m2 treated with ACE inhibitors / ARBs
4. Physiological or surgically menopausal women, women who implement an approved method of contraception
5. Failure in treatment with ACE inhibitors or ARBs to be first 3 months of treatment with RTX
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
1. Serum creatinine> 2.0mg/dl; eGFR <50 ml/min/1.73m2,
2. Previous treatment with rituximab, steroids, alkylating agents, calcineurin inhibitor, ACTH, MMF, azathioprine
3. Presence of active infection
4. Secondary causes of MN (eg hepatitis B, SLE, drugs, tumors). Testing for HIV, hepatitis B and C run less than 6 months before study
5. Diabetes mellitus type 1 and 2
6. Pregnancy or breast-feeding for safety


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

Health Condition(s) or Problem(s) studied

MN is an autoimmune disease, suggesting that the disease may be triggered by isotype specific autoantibodies directed against podocyte enzymes and podocyte receptors that are recognized as antigens. The key role of IgG antibodies formation in the pathogenesis of IMN suggests that B cell depletion may favourably impact the evolution of the glomerular disease and reduce proteinuria. We propose this study in order to test in a randomized controlled trial the hyp
MedDRA version: 14.1 Level: PT Classification code 10018372 Term: Glomerulonephritis membranous System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

Intervention(s)

Trade Name: MABTHERA*EV 1FL 50ML 500MG
Pharmaceutical Form: Solution for injection
CAS Number: 174722-31-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: URBASON*IM EV 1F 250MG+1F 5ML
Pharmaceutical Form: Solution for infusion
CAS Number: 83-43-2
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: MEDROL*10CPR DIV 4MG
Pharmaceutical Form: Tablet
CAS Number: 83-43-2
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: .4-

Trade Name: ENDOXAN BAXTER*50CPR RIV 50MG
Pharmaceutical Form: Coated tablet
CAS Number: 50-18-0
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: .2-

Primary Outcome(s)

Secondary Objective: Differences in terms of:
Levels of proteinuria at time 0, 6.12, 18, 24 and 36 months;
Composite end point of CR (complete remission) or PR (partial remission) at 6, 12, 18, 24, and 36 months;
Mortality ';
Estimated glomerular filtration rate (MDRD formula) at 6, 12, 18, 24, and 36 months;
Value of serum creatinine (mg / dl) at 6, 12, 18, 24, and 36 months;
Frequency and number of relapses;
Frequency of autoantibodies anti-phospholipase A2 receptor (anti-PLA2R), anti-superoxide dismutase 2 (SOD2 anti-), anti-aldose reductase (anti-AR), anti-alpha-enolase (anti-a-enolase) at time 0 and after 3, 6.12, 18, 24 and 36 months after therapy.

Main Objective: The primary outcome was the difference in the probability of complete remission (proteinuria <0.3 g / day) at one year (see design and power considerations).

Primary end point(s): The primary outcome was the difference in the probability of complete remission (proteinuria <0.3 g / day) at one year

Timepoint(s) of evaluation of this end point: one year

Secondary Outcome(s)

Secondary end point(s): Differences in terms of:
Levels of proteinuria at time 0, 6.12, 18, 24 and 36 months;
Composite end point of CR (complete remission) or PR (partial remission) at 6, 12, 18, 24, and 36 months;
Mortality ';
Estimated glomerular filtration rate (MDRD formula) at 6, 12, 18, 24, and 36 months;
Value of serum creatinine (mg / dl) at 6, 12, 18, 24, and 36 months;
Frequency and number of relapses;
Frequency of autoantibodies anti-phospholipase A2 receptor (anti-PLA2R), anti-superoxide dismutase 2 (SOD2 anti-), anti-aldose reductase (anti-AR), anti-alpha-enolase (anti-a-enolase) at time 0 and after 3, 6.12, 18, 24 and 36 months after therapy.

Timepoint(s) of evaluation of this end point: three years

Secondary ID(s)

GNM-2011

Source(s) of Monetary Support

Azienda Spedali Civili di Brescia