Dupilumab Therapy in Nephrotic Syndrome in Children

Not Applicable

Not yet recruiting

• Conditions: Nephrotic Syndrome in Children; Nephrotic Syndrome Steroid-Dependent
• Interventions: Biological: Dupilumab; Drug: Placebo; Biological: Dupilumab open label extension phase; Drug: Co-intervention of Prednisolone wean during randomised controlled phase; Drug: Co-intervention of Prednisolone wean during open label extension phase

• Registration Number: NCT07091175
• Lead Sponsor: National University Hospital, Singapore

Brief 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.

Detailed Description

This is a multi-centre phase II double blinded randomised controlled trial which aims to assess the safety and efficacy of dupilumab for the treatment of steroid dependent or frequently relapsing steroid sensitive nephrotic syndrome in children. Participants will be randomised to receive Dupilumab or placebo via subcutaneous injection for 24 weeks. The primary efficacy end point is time to relapse. Participants who relapse will be unmasked, and if found to have received placebo, will be eligible for the open label extension phase, in which they will receive dupilumab for the following 24 weeks.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-08
• Study First Submitted QC: 2025-07-21
• Last Update Submitted: 2025-07-21
• Study First Posted: 2025-07-29
• Last Update Posted: 2025-07-29
• Study Start: 2025-08-01
• Primary Completion: 2028-02-28
• Study Completion: 2028-02-28

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

1. 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
2. Steroid-dependent disease or frequently relapsing disease prior to commencement of maintenance immunosuppression
3. 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
4. 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
5. In complete remission at the time of recruitment
6. Competent with, and compliant to, daily urine protein monitoring with Albustix

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dupilumab	Dupilumab	Participants in the experimental arm will receive subcutaneous Dupilumab for 24 weeks at the following weight-based doses, which are identical to doses used in the treatment of atopic dermatitis (higher than that for asthma), i.e. * Regime A (15 to \<30kg): 600mg once, then 300mg every 28 days x 5 doses. * Regime B (30 to \<60kg): 400mg once, then 200mg every 14 days x 11 doses. * Regime C (60kg or more): 600mg once, then 300mg every 14 days x 11 doses.
Dupilumab	Co-intervention of Prednisolone wean during randomised controlled phase	Participants in the experimental arm will receive subcutaneous Dupilumab for 24 weeks at the following weight-based doses, which are identical to doses used in the treatment of atopic dermatitis (higher than that for asthma), i.e. * Regime A (15 to \<30kg): 600mg once, then 300mg every 28 days x 5 doses. * Regime B (30 to \<60kg): 400mg once, then 200mg every 14 days x 11 doses. * Regime C (60kg or more): 600mg once, then 300mg every 14 days x 11 doses.
Placebo	Placebo	Participants in the control arm will receive a subcutaneous injection of matched placebo (normal saline) at the same dosing intervals as the experimental arm for 24 weeks.
Open label extension phase	Dupilumab open label extension phase	On relapse, participants will be unmasked. Participants who were randomised to the placebo group will be invited to enrol into an open label extension phase. Participants will receive dupilumab in a regime identical to the experimental arm.
Placebo	Co-intervention of Prednisolone wean during randomised controlled phase	Participants in the control arm will receive a subcutaneous injection of matched placebo (normal saline) at the same dosing intervals as the experimental arm for 24 weeks.
Open label extension phase	Co-intervention of Prednisolone wean during open label extension phase	On relapse, participants will be unmasked. Participants who were randomised to the placebo group will be invited to enrol into an open label extension phase. Participants will receive dupilumab in a regime identical to the experimental arm.

Primary Outcome Measures

Name	Time	Method
Time to relapse	From enrolment until date of relapse, assessed up to 24 weeks	Relapse will be defined as either (a) urine dipstick ≥3+ on 3 consecutive days, with 1x urine protein creatinine ratio ≥200mg/mmol (2000mg/g), or (b) clinical edema in keeping with nephrotic syndrome accompanied by hypoalbuminaemia (serum albumin \<30g/L), with 1x urine protein creatinine ratio ≥200mg/mmol (2000mg/g).; Participants will be expected to record down in a nephrotic diary the urine dipstick result each day, together with the dose of prednisolone taken. Participants are expected to inform the site principal investigator (or designate) if urine dipstick is ≥3+ on 3 consecutive days, and provisions will be made for an ad-hoc urine protein creatinine ratio measurement to determine if relapse has occurred. This should be done within 24 hours of notification by participants.; Participants will also be routinely examined for signs of nephrotic syndrome, for example edema, at study visits, and urine protein creatinine ratio will be obtained at each study visit.

Secondary Outcome Measures

Name	Time	Method
Time-averaged Albustix quantitation of proteinuria during study period	From enrolment until date of relapse, assessed up to 24 weeks	Participants will be requested to record down in a nephrotic diary their urine dipstick result each day, together with the dose of prednisolone taken. The time-averaged albustix quantitation of proteinuria for the study period will then be calculated.
Minimum dose of prednisolone at the end of study	From enrolment until date of relapse, assessed up to 24 weeks	Minimum dose of prednisolone at the end of study - at time of relapse or at 24 weeks, whichever comes first.
Percentage reduction in prednisolone dose at the end of study compared to baseline	At baseline and at time of relapse or at 24 weeks, whichever comes first	Percentage reduction in prednisolone dose at the end of study (at time of relapse or at 24 weeks, whichever comes first) compared to baseline
Change in health-related quality of life at the end of study compared to baseline	At baseline, 1 month, 3 months, 6 months (or at time of relapse, whichever comes first)	Health-related quality of life will be measured using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core scales short form. There are 15 questions, where each question is scored from 0 to 4. The total score ranges from 0 to 60, where a higher score represents a lower quality of life, with more problems associated with coping with health and activities, feelings, getting along with others and work/studies.

Trial Locations

Locations (2)

National University Hospital; 🇸🇬 Singapore, Singapore

KK Women's and Children's Hospital; 🇸🇬 Singapore, Singapore