Efficacy and Safety of Immunoglobulin Associated With Rituximab Versus Rituximab Alone in Childhood-Onset Steroid-dependent Nephrotic Syndrome (RITUXIVIG)

Assistance Publique - Hôpitaux de Paris

Status and phase: Suspended; Phase 3; Phase 2

Conditions: Steroid-Dependent Nephrotic Syndrome

Treatments: Drug: immunoglobulin IV

Study type: Interventional

Funder types: Other

Identifiers

NCT03560011

2017-000826-36 (EudraCT Number)

P160905J

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 2 to 25 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

Rituximab (375 mg/m²)

No Intervention group

Description:

Single infusion of rituximab (375 mg/m²)

Rituximab followed by 5 injections of immunoglobulin IV

Experimental group

Description:

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 dose 100g). Treatment duration : 6 months

Treatment:

Drug: immunoglobulin IV