Dupilumab for nephrotic syndrome in children

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

This study will try dupilumab to help children with steroid‑dependent or frequently relapsing nephrotic syndrome stay in remission and relapse less often.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 6 Years to 18 Years
• Sex: All
• Sponsor: National University Hospital, Singapore (other)
• Drugs / interventions: Rituximab, dupilumab
• Locations: 2 sites (Singapore, Singapore and 1 other locations)
• Trial ID: NCT07091175 on ClinicalTrials.gov

What this trial studies

This is a phase II, double‑blind, randomized placebo‑controlled trial comparing subcutaneous dupilumab to placebo in children with steroid‑dependent or frequently relapsing steroid‑sensitive nephrotic syndrome. Participants receive injections for 24 weeks (every 2 weeks if ≥30 kg or every 4 weeks if <30 kg) while undergoing a supervised prednisolone wean and performing daily urine protein monitoring. The primary endpoint is time to relapse, with safety and adverse events closely recorded during the randomized phase. Children who relapse and were on placebo may enter a 24‑week open‑label extension to receive dupilumab.

Who should consider this trial

Good fit: Children aged 6–18 years with idiopathic steroid‑dependent or frequently relapsing steroid‑sensitive nephrotic syndrome who are in remission, have been on maintenance prednisolone ± mycophenolate or levamisole, and can perform daily urine monitoring are ideal candidates.

Not a fit: Patients with steroid‑resistant disease, non‑idiopathic nephrotic syndrome, certain preexisting eye conditions, active helminth infection, or inability to comply with frequent clinic visits and daily urine checks are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, dupilumab could prolong remission and reduce steroid exposure in affected children.

How similar studies have performed: Applying dupilumab to nephrotic syndrome is relatively novel with preclinical rationale and limited case reports but no large randomized trials demonstrating efficacy to date.

Eligibility criteria

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 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

Where this trial is running

Singapore, Singapore and 1 other locations

• National University Hospital — Singapore, Singapore, Singapore (RECRUITING)
• KK Women's and Children's Hospital — Singapore, Singapore, Singapore (RECRUITING)

Study contacts

• Principal investigator: Hui Kim Yap — National University Hospital, Singapore
• Study coordinator: David Lu

Conditions: Nephrotic Syndrome in Children, Nephrotic Syndrome Steroid-Dependent, Dupilumab, Steroid sensitive nephrotic syndrome, Steroid dependent nephrotic syndrome, Frequently relapsing nephrotic syndrome, Paediatric