Singapore-Malaysian Renal Trials - Nephrotic Syndrome (SMART-NS): Dupilumab Maintenance Therapy for Steroid-dependent and Frequently Relapsing Nephrotic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 66
- 试验地点
- 2
- 主要终点
- Time to relapse
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blinded with open label extension phase for participants who were randomised to placebo and relapsed. Participants will be randomised to receive either dupilumab or placebo. Only the designated unblinded personnel (independent of the study team) will be aware if the participant is receiving dupilumab or placebo, and draw up the correct medication into a syringe to inject into the participant. The participant, their care giver, investigators and outcomes assessor will be blinded. In the open label extension phase, there will be no masking.
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Steroid-dependent disease or frequently relapsing disease prior to commencement of maintenance immunosuppression
- •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
- •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
- •In complete remission at the time of recruitment
- •Competent with, and compliant to, daily urine protein monitoring with Albustix
排除标准
- •Pre-existing ophthalmological conditions except refractive errors, squint or mild cataract
- •Current symptoms of helminth infection or travel to endemic areas, unless helminth infection is excluded
- •eGFR (by Bedside Schwartz equation) <60 ml/min/1.73m2
- •Received Rituximab or other B-cell depleting agents within the last 1 year
- •Biopsy proven focal segmental glomerulosclerosis
- •Known ongoing infection including HIV, Hepatitis B, Hepatitis C or tuberculosis, otherwise immunosuppressed or with frequent infections
- •Known or suspected non-compliance to medication or follow-up
- •Pregnancy or intention to become pregnant
- •Major systemic conditions, i.e. ASA Physical Status III-IV.
- •Known hypersensitivity to dupilumab or any of its excipients
研究组 & 干预措施
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.
干预措施: Dupilumab (Biological)
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.
干预措施: Co-intervention of Prednisolone wean during randomised controlled phase (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Co-intervention of Prednisolone wean during randomised controlled phase (Drug)
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.
干预措施: Dupilumab open label extension phase (Biological)
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.
干预措施: Co-intervention of Prednisolone wean during open label extension phase (Drug)
结局指标
主要结局
Time to relapse
时间窗: 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.
次要结局
- Time-averaged Albustix quantitation of proteinuria during study period(From enrolment until date of relapse, assessed up to 24 weeks)
- Minimum dose of prednisolone at the end of study(From enrolment until date of relapse, assessed up to 24 weeks)
- 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)
- 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))