Dupilumab Therapy in Nephrotic Syndrome in Children

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.

Conditions

• Nephrotic Syndrome in Children
• Nephrotic Syndrome Steroid-Dependent

Interventions

BIOLOGICAL

Dupilumab

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

DRUG

Placebo

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

DRUG

Co-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.

BIOLOGICAL

Dupilumab 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).

DRUG

Co-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.

Sponsors & Collaborators

• National Medical Research Council (NMRC), Singapore

  collaborator OTHER_GOV

• KK Women's and Children's Hospital

  collaborator OTHER_GOV

• National University of Singapore

  collaborator OTHER

• National University Hospital, Singapore

  lead OTHER

Principal Investigators

• Hui Kim Yap · National University Hospital, Singapore

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

6 Years

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-11-27

Primary Completion

2028-02-28

Completion

2028-02-28

Countries

• Singapore

Study Locations