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

NCT00981838 | Completed Phase 3

• 2 other identifiers: NEMO2008-006750-17
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 7

Brief 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

Outcome Measures

Primary Outcomes (1)

• Recurrence of NS.

  1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 month.

Secondary Outcomes (1)

• The dose of immunosuppressive therapy to prevent further NS relapses. Adverse effects of immunosuppressive therapy, such as arterial hypertension and need for antihypertensive therapy, impaired glucose tolerance, dyslipidemia, renal dysfunction. Kidney

  1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 month.

Study Arms (1)

1

EXPERIMENTAL

Rituximab (375 mg/m2).

Drug: Rituximab

Interventions

Rituximab DRUG

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.

1

Eligibility Criteria

• Age: 2 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Agenzia Italiana del Farmaco: collaborator

Study Sites (7)

Hospital "Azienda Ospedaliera Ospedali Riunitidi Bergamo"Unit of Nephrology and Dialysis

Bergamo, Bergamo, 24100, Italy

Location

Hospital "Azienda Ospedaliera santobono-Pausilipon" - Unit of Nephrology and Dialysis

Napoli, Napoli, Italy

Location

Hospital "Azienda Ospedaliero Universitaria Federico II" - Nephrology

Napoli, Napoli, Italy

Location

Hospital "Seconda Università di Napoli" - Policlinico Nuovo

Napoli, Napoli, Italy

Location

Hospital "IRCCS Pediatrico Bambino Gesù di Roma" - Department of Nephrology and Pediatric Urology

Roma, Roma, Italy

Location

Hospital "IRCCS Istituto per l'Infanzia Burlo Garofolo" - Pediatric Nephrology Service

Trieste, Trieste, Italy

Location

Hospital "Ospedale di Cattinara" - Ambulatory of nephrology

Trieste, Trieste, Italy

Location

Related Publications (1)

• Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasa M, Chianca A, Rubis N, Ene-Iordache B, Rudnicki M, Pollastro RM, Capasso G, Pisani A, Pennesi M, Emma F, Remuzzi G; Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014 Apr;25(4):850-63. doi: 10.1681/ASN.2013030251. Epub 2014 Jan 30.

  PMID: 24480824 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Piero Ruggenenti, MD

  Mario Negri Institute for Pharmacological Research

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2009
• First Posted: September 22, 2009
• Study Start: April 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: February 25, 2013

Record last verified: 2013-02

Locations

IT (7)