Clinical trial NCT03560011: Efficacy and Safety of Immunoglobulin Associated With Rituximab Versus Rituximab Alone in Childhood-Onset Steroid-dependent Nephrotic Syndrome
Official title: Efficacy and Safety of Immunoglobulin Associated With Rituximab Versus Rituximab Alone in Childhood-Onset Steroid-dependent Nephrotic Syndrome
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
PHASE3
Conditions: Steroid-Dependent Nephrotic Syndrome
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-06-18
Enrollment: 90
Sex: ALL
Minimum age (years): 2
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 Arms :

* Rituximab (375 mg/m2)
* Rituximab (375 mg/m2) followed by 5 injections of immunoglobulin IV once a month during 5 months (2g/kg at M1, 1.5g/kg at M2 to M5, maximal dise 100g)
Primary purpose: TREATMENT

Brief summary: Idiopathic Nephrotic Syndrome (INS) is the first glomerulopathy in children and 60% of the patients develop Steroid-Dependant Nephrotic Syndrome (SDNS). Recently, rituximab (RTX), a humanized anti-CD20 antibody depleting B cells demonstrated the ability to increase relapse free survival and to decrease the number of relapse and the need of other immunosuppressive drugs. However, the remission rate after 2 years is only 30 to 40%.

The aim of the study is to study the ability of intravenous Immunoglobulin to improve remission rate in SDNS when added associated with Rituximab compared to a treatment by Rituximab alone.

Detailed description: Idiopathic Nephrotic Syndrome (INS) is the first glomerulopathy in children and 60% of the patients develop Steroid-Dependant Nephrotic Syndrome (SDNS). Depleting B cells demonstrated the ability to increase relapse free survival and to decrease the number of relapse and the need of other immunosuppressive drugs. However, the remission rate after 2 years is only 30 to 40%.

The aim of the study is to study the ability of intravenous Immunoglobulin to improve remission rate in SDNS when added associated with Rituximab compared to a treatment by Rituximab alone.

Eligibility criteria: Inclusion Criteria:

* Childhood onset nephrotic syndrome (first flair \<18 years)
* ≥ 2 years old at inclusion
* Steroid-dependent:

  * Patient with at least 2 relapses confirmed during the decay of corticosteroids or within 2 weeks following steroids discontinuation.
  * Patient with at least 2 relapses including one under steroidsparing agent (MMF, Calcineurin inhibitors, cyclophosphamide, Levamisole) or within 6 months of treatment withdrawal.
* or with frequent relapses:

  · 2 or more relapses within 6 months after initial remission or 4 or more relapses within any 12-month period.
* with a relapse within 3 months prior to inclusion
* In remission: Protein-over-creatinine ratio ≤ 0.2g/g (≤ 0.02g/mmol)

Exclusion Criteria:

* Patients with steroid-resistant nephrotic syndrome;
* Patients with genetic nephrotic syndrome;
* Patients previously treated with rituximab;
* Patients with no affiliation to a social security scheme (beneficiary or legal);
* Prior Hepatitis B, Hepatitis C or HIV infection;
* Pregnancy or breastfeeding.
* Patients with hyperprolinaemia,
* Known hypersensitivity to one of the study medication,
* Scheduled and not postponable injection of live attenuated vaccine
* Protected adults
* Patients with neutrophils \< 1.5 G/L and/or platelets \< 75 G/L

Primary outcomes:
measure: The occurrence of the first relapse
timeFrame: 24 months
Secondary outcomes:
measure: Time to first relapse
timeFrame: 24 months
measure: Number of relapse over a 24 months follow-up
timeFrame: 24 months
measure: Cumulative amount of corticosteroid over a 24 months follow-up
timeFrame: 24 months
measure: Adverse events in each arm
timeFrame: 24 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Robert Debre Hospital
Study officials:
affiliation: APHP
name: Julien HOGAN, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hogan J, Perez A, Sellier-Leclerc AL, Vrillon I, Broux F, Nobili F, Harambat J, Bessenay L, Audard V, Faudeux C, Morin D, Pietrement C, Tellier S, Djeddi D, Eckart P, Lahoche A, Roussey-Kesler G, Ulinski T, Boyer O, Plaisier E, Cloarec S, Jolivot A, Guigonis V, Guilmin-Crepon S, Baudouin V, Dossier C, Deschenes G. Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial. BMJ Open. 2020 Sep 23;10(9):e037306. doi: 10.1136/bmjopen-2020-037306.