Rituximab Trial for Pediatric Nephrotic Syndrome (RTX2012)

Seoul National University Childrens Hospital

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Steroid Resistant Nephrotic Syndrome; Steroid Dependent Nephrotic Syndrome

Treatments: Drug: Placebo; Drug: Rituximab

Study type: Interventional

Funder types: Other

Identifiers

NCT01716442

RTX-2012

Details and patient eligibility

About

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.

Enrollment: 88 estimated patients

Sex: All

Ages: 1 to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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88 participants in 3 patient groups, including a placebo group

steroid-resistant

Active Comparator group

Description:

Steroid-resistant group: n=27 , enroll all for treatment

Treatment:

Drug: Rituximab

steroid-dependent-rituximab

Active Comparator group

Description:

steroid-responsive group: n=38

Treatment:

Drug: Rituximab

steroid-dependent-placebo

Placebo Comparator group

Description:

steroid-responsive group: n=23

Treatment:

Drug: Placebo