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Trial record 4 of 6 for:    "Nephrotic Syndrome, Type 2" | "rituximab"

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

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ClinicalTrials.gov Identifier: NCT02394119
Recruitment Status : Unknown
Verified May 2017 by Gian Marco Ghiggeri MD, PhD, Istituto Giannina Gaslini.
Recruitment status was:  Recruiting
First Posted : March 20, 2015
Last Update Posted : May 4, 2017
Sponsor:
Information provided by (Responsible Party):
Gian Marco Ghiggeri MD, PhD, Istituto Giannina Gaslini

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collection and dipstick readings will be carefully reviewed, compliance assessed, and therapy with RAS inhibitors withdrawn and, in hypertensive children replaced by other anti-hypertensive drug.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One week after the steroid withdrawal calcineurin inhibitors will be decreased by 50% and withdrawn within 2 additional weeks.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One week after the steroid withdrawal calcineurin-inhibitors will be decreased by 50% and withdrawn within 2 additional weeks.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


Condition or disease Intervention/treatment Phase
Nephrotic Syndrome Drug: Ofatumumab Drug: Rituximab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ofatumumab
  • Drug Name: Ofatumumab
  • Why: Anti-body/antigen interaction results in cell apoptosis and reduced CD20 positive cell related activities
  • Procedures: methylprednisolone 2 mg/kg infused in 30' IV diluted in 100 ml of normal saline (NaCl 0,9%); oral paracetamol 15 mg/kg ; cetirizine 0,4 mg/kg IV infused slowly in 5 ml of normal saline (NaCl 0,9%) prior to Ofatumumab infusion to reduce common reactions
  • How: Ofatumumab IV: 1500 mg/1.73m2 at 12 ml/hour in the first 30'. Thereafter, the infusion rate can be doubled every 30 minutes up to a maximum of 200 ml/hour.
  • When and how much: once; diluted in 1000 ml of normal saline.
Drug: Ofatumumab
1500 mg/1.73m2, administered once diluted in 1000 ml of normal saline
Other Name: Arzerra

Active Comparator: Rituximab
  • Drug Name: Rituximab (RTX)
  • Why: Anti-body/antigen interaction results in cell apoptosis and reduced CD20 positive cell related activities
  • Procedures: the same as for Ofatumumab Arm
  • How: Rituximab IV: 375 mg/m2; for dosage between 100 and 250 mg RTX will be diluted in 100 ml of normal saline and administered at 2 ml/h for the first 30'; 3 ml/h for the second 30'; 6 ml/h for the third 30'; 15 ml/h until the end. For dosage between 260 and 500 mg RTX will be diluted in 250 ml of normal saline and administered at 6 ml/h for the first 30'; 9 ml/h for the second 30'; 18 ml/h for the third 30'; 36 ml/h until the end. For dosage between 510 and 1000 mg RTX will be diluted in 500 ml of normal saline and administered at 9 ml/h for the first 30'; thereafter, the infusion rate can be doubled every 30 minutes up to a maximum of 72 ml/h.
  • When and how much: once; diluted in 100/250/500 ml of normal saline for dosage respectively between 100-250 mg, 260-500 mg, 510-1000 mg.
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




Primary Outcome Measures :
  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 Outcome Measures :
  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



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 24 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Contacts
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Contact: Gianmarco Ghiggeri, MD +39 010 395214 gmarcoghiggeri@ospedale-gaslini.ge.it

Locations
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Italy
IRCCS Istituto Giannina Gaslini Recruiting
Genoa, Italy/GE, Italy, 16147
Contact: Gian Marco Ghiggeri, MD    0039 010 5636 2419    gmarcoghiggeri@ospedale-gaslini.ge.it   
Principal Investigator: Gian Marco Ghiggeri, MD         
Sub-Investigator: Alice Bonanni, MD         
Sponsors and Collaborators
Istituto Giannina Gaslini
Investigators
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Principal Investigator: Gianmarco Ghiggeri, MD Istituto Giannina Gaslini

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Gian Marco Ghiggeri MD, PhD, MD, director of Nephrology, Dialysis and Transplantation Unit, Istituto Giannina Gaslini
ClinicalTrials.gov Identifier: NCT02394119     History of Changes
Other Study ID Numbers: OFA2
First Posted: March 20, 2015    Key Record Dates
Last Update Posted: May 4, 2017
Last Verified: May 2017
Additional relevant MeSH terms:
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Rituximab
Nephrotic Syndrome
Nephrosis
Syndrome
Disease
Pathologic Processes
Kidney Diseases
Urologic Diseases
Ofatumumab
Antibodies, Monoclonal
Calcineurin Inhibitors
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action