Clinical trial NCT02394119: Ofatumumab Versus Rituximab in Children With Steroid and Calcineurin Inhibitor Dependent Idiopathic Nephrotic Syndrome
Official title: Ofatumumab Versus Rituximab in Children With Steroid and Calcineurin Inhibitor-dependent Idiopathic Nephrotic Syndrome: an Open-label, Randomized, Controlled, Superiority Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nephrotic Syndrome
Lead sponsor: Istituto Giannina Gaslini
Sponsor class: OTHER
First posted: 2015-03-20
Enrollment: 140
Sex: ALL
Minimum age (years): 2
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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urine collection and dipstick readings will be carefully reviewed, compliance assessed, and therapy with RAS inhibitors withdrawn and, in hypertensive children replaced by other anti-hypertensive drug.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One week after the steroid withdrawal calcineurin inhibitors will be decreased by 50% and withdrawn within 2 additional weeks.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One week after the steroid withdrawal calcineurin-inhibitors will be decreased by 50% and withdrawn within 2 additional weeks.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.


Eligibility criteria: 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

Primary outcomes:
measure: Risk of relapse
timeFrame: 12 months
Secondary outcomes:
measure: Amount of steroids required to maintain complete disease remission
timeFrame: 6 and 24 months after Ofatumumab or Rituximab pulse
measure: Adverse events
timeFrame: At 1, 3, 6, 9 ,12, 15, 18, 21 and 24 months after drug infusion, during protocol visits.
measure: Abnormal laboratory values
timeFrame: At 1, 3, 6, 9 ,12, 15, 18, 21 and 24 months after drug infusion, during protocol visits.
Other outcomes:
Locations:
city: Genoa
country: Italy
facility: IRCCS Istituto Giannina Gaslini
state: Italy/GE
Study officials:
affiliation: Istituto Giannina Gaslini
name: Gianmarco Ghiggeri, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Ravani P, Colucci M, Bruschi M, Vivarelli M, Cioni M, DiDonato A, Cravedi P, Lugani F, Antonini F, Prunotto M, Emma F, Angeletti A, Ghiggeri GM. Human or Chimeric Monoclonal Anti-CD20 Antibodies for Children with Nephrotic Syndrome: A Superiority Randomized Trial. J Am Soc Nephrol. 2021 Oct;32(10):2652-2663. doi: 10.1681/ASN.2021040561. Epub 2021 Sep 20.
citation: Ravani P, Bonanni A, Ghiggeri GM. Randomised controlled trial comparing ofatumumab to rituximab in children with steroid-dependent and calcineurin inhibitor-dependent idiopathic nephrotic syndrome: study protocol. BMJ Open. 2017 Mar 17;7(3):e013319. doi: 10.1136/bmjopen-2016-013319.