Dupilumab Therapy in Nephrotic Syndrome in Children

NCT ID: NCT07091175

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-27
• Study Completion Date: 2028-02-28

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.

Conditions

Nephrotic Syndrome in Children; Nephrotic Syndrome Steroid-Dependent

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Dupilumab

Intervention Type: BIOLOGICAL

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

Co-intervention of Prednisolone wean during randomised controlled phase

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Co-intervention of Prednisolone wean during randomised controlled phase

Intervention Type: DRUG

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.

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.

Group Type: OTHER

Dupilumab open label extension phase

Intervention Type: BIOLOGICAL

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).

Co-intervention of Prednisolone wean during open label extension phase

Intervention Type: DRUG

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.

Interventions

Dupilumab

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

Intervention Type: BIOLOGICAL

Placebo

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

Intervention Type: 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.

Intervention Type: DRUG

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).

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Medical Research Council (NMRC), Singapore

OTHER_GOV

Sponsor Role: collaborator

KK Women's and Children's Hospital

OTHER_GOV

Sponsor Role: collaborator

National University of Singapore

OTHER

Sponsor Role: collaborator

National University Hospital, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hui Kim Yap

Role: PRINCIPAL_INVESTIGATOR

National University Hospital, Singapore

Locations

National University Hospital

Singapore, Singapore, Singapore

Site Status: RECRUITING

KK Women's and Children's Hospital

Singapore, Singapore, Singapore

Site Status: RECRUITING

Countries

Singapore

Central Contacts

David Lu

Role: CONTACT

david_lu@nuhs.edu.sg

+65 8044 1290

Facility Contacts

David Lu

Role: primary

david_lu@nuhs.edu.sg

+65 8044 1290

Celeste Jia Ying Yap

Role: primary

celeste.yap.j.y@singhealth.com.sg

+65 8044 1290

References

Chan CY, Teo S, Lu L, Chan YH, Lau PY, Than M, Jordan SC, Lam KP, Ng KH, Yap HK. Low regulatory T-cells: A distinct immunological subgroup in minimal change nephrotic syndrome with early relapse following rituximab therapy. Transl Res. 2021 Sep;235:48-61. doi: 10.1016/j.trsl.2021.03.019. Epub 2021 Apr 1.

Reference Type: BACKGROUND

PMID: 33812063 (View on PubMed)

Lai KW, Wei CL, Tan LK, Tan PH, Chiang GS, Lee CG, Jordan SC, Yap HK. Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats. J Am Soc Nephrol. 2007 May;18(5):1476-85. doi: 10.1681/ASN.2006070710. Epub 2007 Apr 11.

Reference Type: BACKGROUND

PMID: 17429054 (View on PubMed)

Yap HK, Cheung W, Murugasu B, Sim SK, Seah CC, Jordan SC. Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for increased IL-13 mRNA expression in relapse. J Am Soc Nephrol. 1999 Mar;10(3):529-37. doi: 10.1681/ASN.V103529.

Reference Type: BACKGROUND

PMID: 10073603 (View on PubMed)

Other Identifiers

2024/00054

Identifier Type: OTHER

Identifier Source: secondary_id

SMART-NS 01

Identifier Type: -

Identifier Source: org_study_id