Dupilumab Therapy in Nephrotic Syndrome in Children (SMART-NS)

National University Health System (NUHS)

Status and phase: Enrolling; Phase 2

Conditions: Nephrotic Syndrome in Children; Nephrotic Syndrome Steroid-Dependent

Treatments: Biological: Dupilumab; Biological: Dupilumab open label extension phase; Drug: Co-intervention of Prednisolone wean during randomised controlled phase; Drug: Placebo; Drug: Co-intervention of Prednisolone wean during open label extension phase

Study type: Interventional

Funder types: Other

Identifiers

NCT07091175

SMART-NS 01

2024/00054 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 66 estimated patients

Sex: All

Ages: 6 to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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66 participants in 3 patient groups, including a placebo group

Dupilumab

Experimental group

Description:

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.

Treatment:

Drug: Co-intervention of Prednisolone wean during randomised controlled phase

Biological: Dupilumab

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Co-intervention of Prednisolone wean during randomised controlled phase

Open label extension phase

Other group

Description:

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.

Treatment:

Drug: Co-intervention of Prednisolone wean during open label extension phase

Biological: Dupilumab open label extension phase