Ofatumumab Versus Rituximab in Children With Steroid and Calcineurin Inhibitor Dependent Idiopathic Nephrotic Syndrome
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ClinicalTrials.gov Identifier: NCT02394119 |
Recruitment Status :
Completed
First Posted : March 20, 2015
Last Update Posted : July 30, 2020
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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urine collection and dipstick readings will be carefully reviewed, compliance assessed, and therapy with RAS inhibitors withdrawn and, in hypertensive children replaced by other anti-hypertensive drug.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One week after the steroid withdrawal calcineurin inhibitors will be decreased by 50% and withdrawn within 2 additional weeks.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One week after the steroid withdrawal calcineurin-inhibitors will be decreased by 50% and withdrawn within 2 additional weeks.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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Nephrotic Syndrome | Drug: Ofatumumab Drug: Rituximab | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 140 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Ofatumumab Versus Rituximab in Children With Steroid and Calcineurin Inhibitor-dependent Idiopathic Nephrotic Syndrome: an Open-label, Randomized, Controlled, Superiority Trial. |
Study Start Date : | June 2015 |
Actual Primary Completion Date : | June 2018 |
Actual Study Completion Date : | May 2019 |

Arm | Intervention/treatment |
---|---|
Experimental: Ofatumumab
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Drug: Ofatumumab
1500 mg/1.73m2, administered once diluted in 1000 ml of normal saline
Other Name: Arzerra |
Active Comparator: Rituximab
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Drug: Rituximab
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 Name: Mabthera |
- 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).
- 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).
- 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
- 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 2 Years to 24 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02394119
Italy | |
IRCCS Istituto Giannina Gaslini | |
Genoa, Italy/GE, Italy, 16147 |
Principal Investigator: | Gianmarco Ghiggeri, MD | Istituto Giannina Gaslini |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Gian Marco Ghiggeri MD, PhD, MD, director of Nephrology, Dialysis and Transplantation Unit, Istituto Giannina Gaslini |
ClinicalTrials.gov Identifier: | NCT02394119 |
Other Study ID Numbers: |
OFA2 |
First Posted: | March 20, 2015 Key Record Dates |
Last Update Posted: | July 30, 2020 |
Last Verified: | July 2020 |
Nephrotic Syndrome Nephrosis Syndrome Disease Pathologic Processes Kidney Diseases Urologic Diseases |
Rituximab Ofatumumab Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |