Back to resultsIL-2 for Multi Drug Resistant Nephrotic Syndrome
Primary Purpose
Nephrotic Syndrome
Status
Completed
Phase
Phase 1
Locations
Italy
Study Type
Interventional
Intervention
Proleukin®
Sponsored by
About this trial
This is an interventional treatment trial for Nephrotic Syndrome
Eligibility Criteria
Inclusion Criteria:
- Drug resistance: persistence of proteinuria in nephrotic range after a cycle of steroids of at least 3 months and an association with cyclosporine/tacrolimus for at least other 6 months
- Parents'/guardian's written informed consent, and child's assent given before any study-related procedure not part of the subject's normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her future medical care.
- Age between 2 and 18 years
- Histological pattern of minimal change disease, mesangial proliferation with IgM deposits or focal segmental glomerulosclerosis
Exclusion Criteria:
- Positivity to autoimmunity tests (ANA, dsDNA, ANCA).
- Reduction of C3 levels.
- Hystological pattern characterized by elements suggestive for congenital disease: diffuse mesangial sclerosis without IgM deposits, cystic-like tubular dilatation, mitochondrial abnormalities evident on electron microscopy, IF suggestive for congenital collagen 4 disease.
- Histological pattern not suitable with INS in the pediatric age (membranous glomerulonephritis, lupus nephritis, diffuse and/or localized vasculitis, amyloidosis)
- Homozygous or heterozygous mutations of to the 3 genes (NPHS1, NPHS2, WT1) whose mutations are known to be responsible of almost 80% of familiar cases
Sites / Locations
- Istituto Giannina Gaslini
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Proleukin®
Arm Description
Subcutaneous administration of low doses of IL2 (Proleukin) following the therapeutical scheme indicated for crioglobulinemic nephropathy: cycle1: IL2 1x106 /m2 s.c for 5 consecutive days cycle2: IL2 1.5 x106 / m2 s.c for 5 consecutive days, starting from 3 weeks after the first cycle. cycle3: IL2 1.5 x106 /m2 s.c for 5 consecutive days, starting from 6 weeks after the first cycle. Cycle 4: IL2 1.5 x106 /m2 s.c for 5 consecutive days, starting from 9 weeks after the first cycle.
Outcomes
Primary Outcome Measures
Proteinuria
Complete remission is defined by urinary protein/creatinine ratio (uPCR) <200 mg/g (<20mg/mmol) for 3 consecutive days. Partial remission is defined as proteinuria reduction of 50% or greater from the presenting value and absolute uPCR between 200 and 2000 mg/g. for 3 consecutive days.
Secondary Outcome Measures
Tregs Levels
Serum Creatinine
Adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02455908
Brief Title
IL-2 for Multi Drug Resistant Nephrotic Syndrome
Official Title
Use of IL-2 for Pediatric, Multi Drug Resistant, Idiopathic Nephrotic Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Istituto Giannina Gaslini
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of the study is to design an open-label phase 1-2 trial to assess safety and clinical and immunologic effects of repeated administration of recombinant low dose IL2 (Proleukin) in 5 patients with idiopathic nephrotic syndrome unresponsive to drugs (steroids, calcineurin inhibitors, Rituximab), following the therapeutical scheme indicated for crioglobulinemic nephropathy:
cycle1: IL2 1x106 /m2 s.c for 5 consecutive days cycle2: IL2 1.5 x106 / m2 s.c for 5 consecutive days, starting from 3 weeks after the first cycle.
cycle3: IL2 1.5 x106 /m2 s.c for 5 consecutive days, starting from 6 weeks after the first cycle.
Cycle 4: IL2 1.5 x106 /m2 s.c for 5 consecutive days, starting from 9 weeks after the first cycle.
Current therapy with steroids and calcineurin inhibitors (Prograf) will be maintained during the first cycle and progressively reduced during the subsequent cycles.
The first cycle will be performed during hospitalization in the investigators Unit; subsequent cycles will be performed at nephrology outpatients. All laboratory values normally utilized in the follow up of patients affected by idiopathic nephrotic syndrome will be evaluated during the first week of treatment and at the end of the protocol, together with specific cellular values (Tregs, B cells, NK).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nephrotic Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Proleukin®
Arm Type
Experimental
Arm Description
Subcutaneous administration of low doses of IL2 (Proleukin) following the therapeutical scheme indicated for crioglobulinemic nephropathy:
cycle1: IL2 1x106 /m2 s.c for 5 consecutive days cycle2: IL2 1.5 x106 / m2 s.c for 5 consecutive days, starting from 3 weeks after the first cycle.
cycle3: IL2 1.5 x106 /m2 s.c for 5 consecutive days, starting from 6 weeks after the first cycle.
Cycle 4: IL2 1.5 x106 /m2 s.c for 5 consecutive days, starting from 9 weeks after the first cycle.
Intervention Type
Drug
Intervention Name(s)
Proleukin®
Other Intervention Name(s)
IL-2
Primary Outcome Measure Information:
Title
Proteinuria
Description
Complete remission is defined by urinary protein/creatinine ratio (uPCR) <200 mg/g (<20mg/mmol) for 3 consecutive days. Partial remission is defined as proteinuria reduction of 50% or greater from the presenting value and absolute uPCR between 200 and 2000 mg/g. for 3 consecutive days.
Time Frame
Change from baseline at 30, 60 and 180 days after first cycle (5 days)
Secondary Outcome Measure Information:
Title
Tregs Levels
Time Frame
Immediately before first cycle and 30, 60 and 180 days after first cycle (5 days)
Title
Serum Creatinine
Time Frame
Change from baseline at 30, 60 and 180 days after first cycle (5 days)
Title
Adverse events
Time Frame
From day 1 to day 5 of each cycle. The study includes 5 cycles, each one lasting 5 days.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Drug resistance: persistence of proteinuria in nephrotic range after a cycle of steroids of at least 3 months and an association with cyclosporine/tacrolimus for at least other 6 months
Parents'/guardian's written informed consent, and child's assent given before any study-related procedure not part of the subject's normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her future medical care.
Age between 2 and 18 years
Histological pattern of minimal change disease, mesangial proliferation with IgM deposits or focal segmental glomerulosclerosis
Exclusion Criteria:
Positivity to autoimmunity tests (ANA, dsDNA, ANCA).
Reduction of C3 levels.
Hystological pattern characterized by elements suggestive for congenital disease: diffuse mesangial sclerosis without IgM deposits, cystic-like tubular dilatation, mitochondrial abnormalities evident on electron microscopy, IF suggestive for congenital collagen 4 disease.
Histological pattern not suitable with INS in the pediatric age (membranous glomerulonephritis, lupus nephritis, diffuse and/or localized vasculitis, amyloidosis)
Homozygous or heterozygous mutations of to the 3 genes (NPHS1, NPHS2, WT1) whose mutations are known to be responsible of almost 80% of familiar cases
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gian Marco Ghiggeri, MD
Organizational Affiliation
Istituto Giannina Gaslini
Official's Role
Principal Investigator
Facility Information:
Facility Name
Istituto Giannina Gaslini
City
Genova
ZIP/Postal Code
16147
Country
Italy
12. IPD Sharing Statement
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IL-2 for Multi Drug Resistant Nephrotic Syndrome
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