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NCT Number: NCT02394119

Ofatumumab Versus Rituximab in Children With Steroid and Calcineurin Inhibitor Dependent Idiopathic Nephrotic Syndrome

Open-label, two-parallel-arm, controlled randomized clinical trial testing the superiority of Ofatumumab over Rituximab in maintaining steroid- and calcineurin-inhibitor-free disease remission in SD-INS.

Eligible participants will enter a 1-month run-in period, during which instruction on urine collection and dipstick readings will be carefully reviewed, compliance assessed, and therapy with RAS inhibitors withdrawn and, in hypertensive children replaced by other anti-hypertensive drug.

After run-in period, children will be randomized to either the intervention arm (Ofatumumab) or the comparator arm (Rituximab).

After infusion of intervention or comparator, steroids will be maintained at initial dose for 30 days and then tapered off by 0.3 mg/kg per week until complete withdrawal.

One week after the steroid withdrawal calcineurin inhibitors will be decreased by 50% and withdrawn within 2 additional weeks.

All patients will be followed for up to 24 months. In case of relapses during the study (see outcome section for definition) patients will be treated with 60 mg/m2of prednisone p.o. in order to achieve remission. At remission, patients will be treated with another infusion of either Oftumumab or Rituximab, according to the initial randomization.

After infusion of intervention or comparator, steroids will be maintained at initial dose for 30 days and then tapered off by 0.3 mg/kg per week until complete withdrawal.

One week after the steroid withdrawal calcineurin-inhibitors will be decreased by 50% and withdrawn within 2 additional weeks. This strategy will be repeated to treat full relapses during the study.

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Key information

Conditions

Nephrotic Syndrome Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Nephrosis Urogenital Diseases Urologic Diseases

Age range

2 year–24 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

IRCCS Istituto Giannina Gaslini

Genoa, Italy/GE, 16147, Italy

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

To be eligible for inclusion into this study, participants will have to fulfill the following criteria:

  • To be in complete disease remission
  • Drug dependence: remission has to be maintained with both steroids and CNI steroid dependence is defined by two consecutive relapses during corticosteroid therapy or within 14 days of ceasing therapy. CNI (cyclosporine/tacrolimus) dependence is defined by presence of relapse at discontinuation.
  • Ability to provide consent and assent: parents'/guardian's written informed consent, and child's assent given before any study-related procedure not part of the subject's normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her future medical care.
  • Age between 2 and 24 years

Exclusion criteria

Children will be excluded if any of the following criteria apply:

  • Positivity to autoimmunity tests (ANA, nDNA, ANCA)
  • Reduction of C3 levels.
  • eGFR<90/ml/min/1,73 m2 valuated according to revised Bedside Schwartz Formula for patients between 2 and 17 years and with CKD-EPI Creatinine 2009 Equation for 18 years old patients.
  • Pregnancy
  • Neoplasm
  • Infections: previous or actual HBV (with HBeAb positivity) or HCV infection
  • CD20 B lymphocytes count <2,5%
  • Treatment with Rituximab or cyclophosphamide in the last 6 months

Treatment and study plan

ofatumumab

Drug

1500 mg/1.73m2, administered once diluted in 1000 ml of normal saline

Other names: Arzerra

Rituximab

Drug

375 mg/m2, administered once diluted in 100/250/500 ml of normal saline for dosage respectively between 100-250 mg, 260-500 mg, 510-1000 mg.

Other names: Mabthera

Primary outcomes

  1. Risk of relapse

    Time frame: 12 months

    The primary endpoints will be risk of relapse at 12 months without steroid or calcineurin-inhibitors. Relapse is defined by uPCR ≥2000 mg/g (≥ 200 mg/mmol) or > 3+ protein on urine dipstick for 3 consecutive days (KDIGO Clinical Practice Guideline for Glomerulonephritis, Kidney International Supplement, 2012 2, 163-171).

Secondary outcomes

  1. Amount of steroids required to maintain complete disease remission

    Time frame: 6 and 24 months after Ofatumumab or Rituximab pulse

    Complete remission is defined by uPCR <200 mg/g (<20 mg/mmol) or o1+ of protein on urine dipstick for 3 consecutive days (KDIGO Clinical Practice Guideline for Glomerulonephritis, Kidney International Supplement, 2012 2, 163-171).

  2. Adverse events

    Time frame: At 1, 3, 6, 9 ,12, 15, 18, 21 and 24 months after drug infusion, during protocol visits.

    Measurement of frequency and severity of adverse events due to drug infusion

  3. Abnormal laboratory values

    Time frame: At 1, 3, 6, 9 ,12, 15, 18, 21 and 24 months after drug infusion, during protocol visits.

    Record of abnormal values in biochemical tests and hematology assessments due to drug infusion

Sponsors and collaborators

Lead sponsor

Istituto Giannina Gaslini

Other

Registry information

Official study title

Ofatumumab Versus Rituximab in Children With Steroid and Calcineurin Inhibitor-dependent Idiopathic Nephrotic Syndrome: an Open-label, Randomized, Controlled, Superiority Trial.

Important dates

Study start
2015
Primary completion
2018
Study completion
2019
First posted
Mar 20, 2015
Registry last updated
Jul 30, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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