Nephrotic Syndrome Steroid-Dependent Clinical Trial
Official title:
Efficacy of Chimeric Monoclonal Anti-CD20 Antibodies (Rituximab Biosimilar) in the Treatment of Childhood Steroid-dependent Nephrotic Syndrome and Development of Cell Biomarkers Predicting Outcome. The RTX 4 Trial.
Anti-CD20 monoclonal antibodies are emerging as the steroid-sparing therapy of choice for
nephrotic syndrome.
This Randomized Clinical Trial seeks to evaluate whether Rituximab biosimilar maintains
drug-free disease remission in patientswith steroid-dependent nephrotic syndrome for 12-24
months and verify its superiority vs. mycophenolate mofetil, the reference standard therapy.
The investigators will compare the risk of relapse to test this hypothesis (primary outcome).
Secondary objectives will include assessing short- and long-term side-effects and developing
specific biomarkers of sensitivity to therapy. Patients will be recruited, treated and
followed at IRCCS G Gaslini and IRCCS Bambino Gesù where laboratory studies will be performed
at in-site facilities
Idiopathic nephrotic syndrome (NS) is characterized by proteinuria and hypoalbuminemia
associated with dyslipidemia and hypercoagulability. Oral corticosteroids are the cornerstone
of therapy and induce disease remission in approximately 90% of cases. However, up to 85% of
patients relapse and many develop steroid dependence (SDNS), requiring prolonged dose of
steroids to maintain remission. Clinical practice guidelines (KDIGO) suggest using low-dose
prednisone to maintain remission in SDNS and Mycophenolate Mofetil (MMF) or calcineurin
inhibitors (CNI) as corticosteroid-sparing agents for children who develop steroid adverse
effects. Given the toxicity of all these drugs (steroids, CNI and MMF), there is a need to
investigate alternative options. Recent evidence supports the use of chimeric anti-CD20
monoclonal antibodies in simple SDNS (Rituximab, RTX).
The RTX4 trial is an open-label, two-parallel-arm, controlled and randomized clinical trial
testing the superiority of RTX over MMF in maintaining steroid free disease remission in
patients with SDNS.
Eligible participants are children and young adults (age between 3 and 24 years) with
nephrotic syndrome who are dependent on prednisone 0.3-1mg/Kg/day and have received
prednisone for at least six months before enrolment. Previous treatment with MMF will be
allowed. All participants will enter a 45 days run-in period, during which children treated
with steroids alone will start MMF 1,200 mg/1,73 sqm orally in 2 daily doses and will taper
steroids after 15 days by 0.3 mg/kg per week until complete withdrawal. Patients already
receiving MMF alone will continue the treatment. During the same period, instruction on urine
collection and dipstick readings will be carefully reviewed and compliance assessed. After
run-in period, children will be randomized to either the intervention arm (Rituximab,
375mg/m2) or the comparator arm (continuing or starting MMF). In the intervention arm, 1
month after infusion MMF will be decreased by 50% and withdrawn within 2 additional weeks,
whereas MMF will be maintained in the comparator. All patients will be followed for up to 24
months. In case of relapses during this period (see outcome section for definition) patients
will be treated with oral prednisone (60 mg/sqm day). Following remission, steroids will be
maintained at the initial dose for 7 days and then tapered off by 0.3 mg/kg per week until
complete withdrawal in patients of the MMF arm. Patients of the intervention arm will instead
be treated with another infusion of RTX (same dose) immediately following steroid-induced
remission. After infusion of RTX, steroids will be maintained at the initial dose for 7 days
and then tapered off by 0.3 mg/kg per week until complete withdrawal. In this way relapsed
patients in both arms will receive the same cumulative dose of prednisone. In case following
relapse of proteinuria patients fail to respond to prednisone (they will terminate the study
and be considered as treatment failure). The study allows drop-in from one arm to the other
after 3 relapses (i.e., investigators will be allowed to use RTX in the comparator arm and
vice versa MMF in intervention arm). The economic balance will be calculated on the basis of
RTX doses needed to maintain remittance.
All patients will be followed for 24 months. In person visits will occure at enrollment, at
T0 (infusion), after 1 month and every 3/6 months later.
The investigators are going to enroll 160 patients.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT04585152 -
Rituximab Versus Mycophenolate Mofetil in Children With Steroid-dependent Idiopathic Nephrotic Syndrome.
|
Phase 2 | |
| Withdrawn |
NCT02997150 -
Treatment of Steroid Dependent Idiopathic Nephrotic Syndrome in Children With Low Doses of Interleukin 2: a Pilot Study
|
Phase 2 |