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

• Status: Completed
• Trial end date: 2011-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborator: Agenzia Italiana del Farmaco
• Treatments: Rituximab

Criteria

Inclusion criteria:

• Males and females

• Steroid-dependent or multirelapsing NS (defined on the basis of the occurrence of more than 2 relapses in the previous year in spite of steroid and/or other immunosuppressive therapy). Only patients reported to invariably relapse upon treatment tapering or withdrawal who are on stable (from at least 1 month) complete (<0.3 g/24h for adults or <4 mg/h/m2 for children) or partial (<3.5 g/24h for adults or <40 mg/h/m2 for children) remission of the NS will be included;

• Histological diagnosis of MCD or FSGS or mesangial proliferative GN;

• Written informed consent (or consent from parents or tutors for underage patients).

Exclusion criteria:

• Advanced renal failure (creatinine clearance less than 20 ml/min/1.73m2);

• Evidence of B or C virus infection;

• Refractory or persistent NS;

• Genetic mutations associated with intrinsic abnormalities of the glomerular barrier that would hardly be affected by rituximab treatment;

• Pregnancy or lactating;

• Women of childbearing potential without following a scientifically accepted form of contraception;

• Legal incapacity;

• Evidence of an uncooperative attitude;

• Previous diagnosis of: intellectual disability/mental retardation, dementia, schizophrenia.

• Any evidence that patient will not be able to complete the trial follow-up.