Study protocol: multicenter double-blind, randomized, placebo-controlled trial of rituximab for the treatment of childhood-onset early-stage uncomplicated frequently relapsing or steroid-dependent nephrotic syndrome (JSKDC10 trial)

BMC Nephrol. 2019 Aug 2;20(1):293. doi: 10.1186/s12882-019-1470-3.

Abstract

Background: Eighty percent of children with idiopathic nephrotic syndrome respond well to steroid therapy, but up to 50% of patients with steroid-sensitive nephrotic syndrome exhibit frequently relapsing (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Several studies identified the chimeric anti-CD20 monoclonal antibody rituximab as an effective treatment for patients with complicated FRNS/SDNS. Recent studies suggested that rituximab could also be a first-line treatment for early-stage uncomplicated FRNS/SDNS, although further studies are required to confirm its efficacy and safety.

Methods/design: We are conducting a multicenter, double-blind, randomized placebo controlled trial to investigate the efficacy and safety of rituximab for the treatment of childhood-onset early-stage uncomplicated FRNS/SDNS. Patients will be allocated to receive two 375 mg/m2 doses (maximum dose: 500 mg) of either rituximab or placebo. Investigators are permitted to request the disclosure of a subject's allocation code if he or she exhibits treatment failure. Additionally, if placebo-treated subjects display early relapse (a sign of treatment failure), they have the option to receive rituximab in an unblinded phase. The primary endpoint is relapse-free survival during the observation period.

Discussion: The results will provide important data on the use of rituximab for patients with uncomplicated FRNS/SDNS. In the future, rituximab treatment will enable most patients with uncomplicated FRNS/SDNS to discontinue or reduce steroid therapy without relapse, and it is possible that rituximab could represent an immunosuppressive therapy for these diseases.

Trial registration: This trial was prospectively registered to the JMACCT Clinical Trials Registry on September 6, 2018 (Trial ID: JMA-IIA00380 ).

Keywords: Frequently relapsing nephrotic syndrome; Rituximab; Steroid-sensitive nephrotic syndrome.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Double-Blind Method
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / therapeutic use*
  • Japan
  • Multicenter Studies as Topic
  • Nephrotic Syndrome / drug therapy*
  • Placebos / therapeutic use
  • Randomized Controlled Trials as Topic*
  • Recurrence
  • Rituximab / administration & dosage
  • Rituximab / therapeutic use*
  • Sample Size
  • Steroids / pharmacology

Substances

  • Immunologic Factors
  • Placebos
  • Steroids
  • Rituximab