RecruitingPhase 2NCT07091175

Dupilumab Therapy in Nephrotic Syndrome in Children

Singapore-Malaysian Renal Trials - Nephrotic Syndrome (SMART-NS): Dupilumab Maintenance Therapy for Steroid-dependent and Frequently Relapsing Nephrotic Syndrome

Sponsor

National University Hospital, Singapore

Enrollment

66 participants

Start Date

Nov 27, 2025

Study Type

INTERVENTIONAL

Conditions

Nephrotic Syndrome in Children Nephrotic Syndrome Steroid-Dependent

Summary

The goal of this clinical trial is to learn if dupilumab works to treat severe nephrotic syndrome in children. It will also learn about the safety of dupilumab. The main questions it aims to answer are: * Does dupilumab reduce the time to relapse of nephrotic syndrome? * What medical problems do participants have when taking dupilumab? Researchers will compare dupilumab to a placebo (a look-alike substance that contains no drug) to see if dupilumab works to treat severe nephrotic syndrome. Participants will: * Receive an injection of dupilumab or placebo (just under the skin) every 2 weeks (if ≥30kg) or every 4 weeks (if \<30kg) for 24 weeks (6 months) * Wean down their prednisolone dose after starting the injections of dupilumab or placebo * Visit the clinic once every 2 weeks for checkups and tests * Keep a nephrotic diary to record down the urine dipstick result each day, together with the dose of prednisolone taken If protein returns in participant's urine, they will have completed the study at that point. However, if the participant is found to have received the placebo, they will be offered to receive dupilumab for up to 24 weeks.

Eligibility

Min Age: 6 YearsMax Age: 18 Years

Inclusion Criteria6

Age between 6 years old and 18 years old at the point of recruitment with idiopathic nephrotic syndrome with disease onset between 1-18 years old
Steroid-dependent disease or frequently relapsing disease prior to commencement of maintenance immunosuppression
On oral prednisolone +/- mycophenolate or levamisole only as maintenance therapy for 6 months or more, and with inadequate disease control or steroid toxicity on therapy
Nephrotic relapse or partial relapse (clinical or biochemical) within the last 1 year either unprovoked or during prednisolone wean, and which responded to increase in steroids
In complete remission at the time of recruitment
Competent with, and compliant to, daily urine protein monitoring with Albustix

Exclusion Criteria10

Pre-existing ophthalmological conditions except refractive errors, squint or mild cataract
Current symptoms of helminth infection or travel to endemic areas, unless helminth infection is excluded
eGFR (by Bedside Schwartz equation) \<60 ml/min/1.73m2
Received Rituximab or other B-cell depleting agents within the last 1 year
Biopsy proven focal segmental glomerulosclerosis
Known ongoing infection including HIV, Hepatitis B, Hepatitis C or tuberculosis, otherwise immunosuppressed or with frequent infections
Known or suspected non-compliance to medication or follow-up
Pregnancy or intention to become pregnant
Major systemic conditions, i.e. ASA Physical Status III-IV.
Known hypersensitivity to dupilumab or any of its excipients

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Interventions

BIOLOGICALDupilumab

Subcutaneous injection of Dupilumab for 24 weeks (weight based dosing)

DRUGPlacebo

Subcutaneous injection of normal saline placebo (matching dupilumab subcutaneous injection dosing) for 24 weeks

DRUGCo-intervention of Prednisolone wean during randomised controlled phase

The Prednisolone wean will commence 2 weeks after receiving the loading dose of Dupilumab/placebo, with each weaning step 2 weeks apart. Prednisolone will be first weaned to the same dose every other day, if the current dosing is daily (or more frequent). The dose will subsequently weaned to 4 pre-determined levels of 30mg/m2, 15mg/m2, 10mg/m2 and 5mg/m2 every other day, rounding up to the nearest 5mg. For instance, if the current dose of prednisolone is 12mg/m2 every other day, the patient will decrease the dose to 10mg/m2 every other day for 2 weeks, followed by 5mg/m2 every other day for 2 weeks, before discontinuing the drug. If patients enter the trial on Mycophenolate or Levamisole, this will be continued for the duration of the trial at the same dose.

BIOLOGICALDupilumab open label extension phase

Upon nephrotic relapse, participants will be unmasked. If they were given placebo, they will be invited to enrol in an open label extension phase to receive dupilumab for 24 weeks (with dosing identical to the experimental arm).

DRUGCo-intervention of Prednisolone wean during open label extension phase

Patients will also receive prednisolone 60mg/m2/day as a single daily dose (max 60-80mg OD according to physician's discretion) until in remission for 3 days, before prednisolone is weaned to 40mg/m2 every other day for 2 weeks. Doses should be rounded up to nearest 5mg where possible. Prednisolone will then be weaned in steps as per the randomised controlled phase. If patients do not enter full remission after 2 weeks from enrolment into the extension phase, they will be removed from the study. Additional agents, e.g. Mycophenolate, Levamisole, Calcineurin inhibitors should not be started during this time unless there is strong clinical indication.