Rituximab in Multirelapsing Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS)

Summary

Background. Patients, especially children, with steroid-dependent or multirelapsing nephrotic syndrome (NS) secondary to minimal change disease (MCD) or idiopathic focal and segmental glomerulosclerosis (FSGS) on continuous treatment with steroids and/or other immunosuppressive agents to limit or prevent recurrences are at increased risk of severe drug-related adverse events. Case reports suggest that Rituximab, a B cell depleting monoclonal antibody, could be a safe and effective alternative to steroid or immunosuppressants to achieve and maintain remission in this population.

Objectives. The study is primarily aimed at evaluating whether Rituximab may maintain stable NS remission after tapering and withdrawal of steroid and immunosuppressive therapy in patients with MCD or FSGS and steroid-dependent or multirelapsing NS. Secondarily, the study will assess whether Rituximab allows reducing maintenance doses of steroids and other immunosuppressants (in those who relapse), thus limiting treatment related side effects and costs.

Methods. This prospective, sequential, open, study will include 20 patients with histology evidence of MCD or FSGS and steroid-dependant or multirelapsing NS, who are on stable complete or partial remission since at least 1 month and, based on their previous history, are expected to invariably relapse after steroid/immunosuppression withdrawal. After baseline evaluation of clinical, laboratory and kidney function parameters \[including glomerular filtration rate (GFR), renal plasma flow (RPF), albumin and sodium fractional clearance and the glomerular albumin permeability assay (Palb)\], patients will receive one Rituximab infusion that will be repeated 1 week later if CD20 cells are not fully depleted from the circulation. Then ongoing immunosuppression will be progressively tapered up to complete withdrawal over 6 to 9 months. 24h proteinuria will be monitored monthly and spot urine will be tested daily by albustix to early detect disease relapses. Baseline evaluations will be repeated at study end (1 year). Relapses will be treated with high-dose steroids as per center practice and the last immunosuppressive therapy effective in preventing disease reactivation will be reintroduced.

Expected results. Rituximab is expected to prevent NS recurrence following tapering and discontinuation of steroid and other immunosuppressants. Maintaining remission without chronic immunosuppression is expected to minimize risks and costs of therapy and to remarkably improve patient outcomes.

Conditions

• Nephrotic Syndrome

Interventions

DRUG

Rituximab

Rituximab (375 mg/m2) will be given as a single intravenous infusion after reconstitution in normal saline to a concentration of 1 mg/ml given though a 0.22 micron in line filter. The initial infusion rate will be 1 ml/kg/h and will be progressively increased up to 4 ml/kg/h according to drug tolerability. Pre-medication with steroids and/or antihistaminic agents will be done according to per-center's practice.Rituximab administration will be repeated in those patients \> 5 B cells/mm3 in the peripheral blood on the day after first Rituximab administration.

Sponsors & Collaborators

• Agenzia Italiana del Farmaco

  collaborator OTHER_GOV

• Mario Negri Institute for Pharmacological Research

  lead OTHER

Principal Investigators

• Piero Ruggenenti, MD · Mario Negri Institute for Pharmacological Research

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

2 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-04-30

Primary Completion

2011-04-30

Completion

2011-04-30

Countries

• Italy

Study Locations