IL-2 for Multi Drug Resistant Nephrotic Syndrome

Phase 1

Completed

• Conditions: Nephrotic Syndrome
• Interventions: Drug: Proleukin®

• Registration Number: NCT02455908
• Lead Sponsor: Istituto Giannina Gaslini

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2012-02
• Primary Completion: 2012-08
• Study Completion: 2012-08
• Status Verified: 2015-05
• Study First Submitted: 2015-05-13
• Study First Submitted QC: 2015-05-27
• Last Update Submitted: 2015-05-27
• Study First Posted: 2015-05-28
• Last Update Posted: 2015-05-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

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any study-related procedure not part of the subject's normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her future medical care.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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Proleukin®	Proleukin®	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.

Primary Outcome Measures

Name	Time	Method
Proteinuria	Change from baseline at 30, 60 and 180 days after first cycle (5 days)	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

Name	Time	Method
Tregs Levels	Immediately before first cycle and 30, 60 and 180 days after first cycle (5 days)
Serum Creatinine	Change from baseline at 30, 60 and 180 days after first cycle (5 days)
Adverse events	From day 1 to day 5 of each cycle. The study includes 5 cycles, each one lasting 5 days.

Trial Locations

Locations (1)

Istituto Giannina Gaslini; 🇮🇹 Genova, Italy