Rituximab Trial for Pediatric Nephrotic Syndrome (RTX2012)

A Multi-center Randomized Controlled Trial of Rituximab for Refractory Nephrotic Syndrome in Children

Anti-CD20 agent has been proposed as a rescue therapy for refractory nephrotic syndrome(NS) on the basis of favorable clinical observations. Yet the long-term effect on maintaining remission or the likelihood of becoming rituximab-dependent is unclear and the information on the safety profile of rituximab is limited. This trial was designed to investigate the safety and efficacy of Rituximab in children with refractory NS.

Study Overview

• Status: Unknown
• Conditions: Steroid Resistant Nephrotic Syndrome; Steroid Dependent Nephrotic Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Rituximab

• Study Type: Interventional
• Enrollment (Anticipated): 88
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-740
    • Recruiting
    • Seoul National University Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

(A)steroid/calcineurin inhibitor resistant nephrotic syndrome

1. steroid resistance: no remission after 4 weeks of daily oral corticosteroid (60mg/m2/day)
2. calcineurin inhibitor resistance: no remission after 3 months of therapeutic dose administration of cyclosporine and/or tacrolimus
3. no remission defined by persistent proteinuria of nephrotic range for the last 3 months
4. post-transplant patients were included in the study

(B)steroid-dependent nephrotic syndrome

1. Steroid-dependent patients who had been on various known medications (such as corticosteroids, cyclophosphamide, chlorambucil, calcineurin inhibitors, levamisole ..) continuously for more than 2 years

2. definition of dependency: more than two consecutive relapse events in 2 weeks after discontinuation of steroid or calcineurin inhibitor

   • no improvement in relapsing frequency with calcineurin inhibitor use
   • unable to continue with calcineurin inhibitor due to side effects
   • unable to continue with calcineurin inhibitor due to prolonged use (over 2 years)
   • other conditions in which the clinician considers difficult to control disease with steroids or calcineurin inhibitors only.

Exclusion Criteria:

• previous rituximab use
• secondary nephrotic syndrome
• estimated GFR <60mL/min/1.73m2 or under 50% of age-matched standard GFR
• chronic or acute active infection (e.g. hepatitis B,C, herpes, varicella zoster)
• prior live vaccine inoculation within 1 month (from the study enrollment)
• cardiovascular diseases, pulmonary or pleural diseases
• uncontrolled hypertension
• leukocytopenia (absolute neutrophil count <1500/mm3) or thrombocytopenia (<75000/mm3)
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: steroid-resistant; Steroid-resistant group: n=27 , enroll all for treatment	Drug: Rituximab; Per dose: Rituximab 375 mg/m2 (max.500mg/day). efficacy monitored by CD19 cell count. If CD19 cells are not depleted, second or third doses are given at 2-3 weeks interval.; Other Names: Mabthera; 2005110300291 (rituximab)
Active Comparator: steroid-dependent-rituximab; steroid-responsive group: n=38	Drug: Rituximab; Per dose: Rituximab 375 mg/m2 (max.500mg/day). efficacy monitored by CD19 cell count. If CD19 cells are not depleted, second or third doses are given at 2-3 weeks interval.; Other Names: Mabthera; 2005110300291 (rituximab)
Placebo Comparator: steroid-dependent-placebo; steroid-responsive group: n=23	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The remission rate of steroid-resistant nephrotic syndrome patients after rituximab treatment	within 6 months from the initiation of treatment
The rate of maintaining remission in steroid-dependent nephrotic syndrome patients	within 6 months from the initiation of treatment versus placebo control

Collaborators and Investigators

• Sponsor: Seoul National University Childrens Hospital
• Investigators: Principal Investigator: Hee Gyung Kang A. Kang, M.D., Ph.D., Seoul National University Children's Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Anticipated): September 1, 2013
• Study Completion (Anticipated): November 1, 2013

Study Registration Dates

• First Submitted: October 25, 2012
• First Submitted That Met QC Criteria: October 26, 2012
• First Posted (Estimate): October 29, 2012

Study Record Updates

• Last Update Posted (Estimate): October 29, 2012
• Last Update Submitted That Met QC Criteria: October 26, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: rituximab; refractory; nephrotic
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Syndrome; Nephrotic Syndrome; Nephrosis; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: RTX-2012