A Phase 2 Open-label Study to Evaluate the Efficacy of Allogeneic Human Cord Blood-derived Mesenchymal Stromal Cells in Maintaining Remission After Immunosuppressive Therapy Withdrawal in Pediatric Patients With Steroid-dependent Nephrotic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- The percentage of patients without nephrotic syndrome recurrence after complete withdrawal of immunosuppressive treatment for at least 6 months
研究概览
简要总结
A phase II open-label, single arm study aimed to ascertain whether infusions of cord-blood mesenchymal stromal cells (CB-MSCs) allow to reduce or suspend the chronic immunosuppressive therapy (IS) in steroid-dependent nephrotic syndrome (SDNS).
We plan to enroll 11 patients aged 3 to 18 with SDNS in remission for at least one month, maintained by either ≥2 immunosuppressive drugs or a calcineurin inhibitor.
Patients are infused with cord-blood allogenic MSC, selected by in-vitro alloreactivity, at a dose of 1.5x10^6/kg on days 0, 14, 21. The immunosuppressive treatment is gradually tapered starting at the first CB-MSC administration, according to the following scheme: 25% following the first administration, 50% following the second administration, and 100% reduction following the third administration.
All patients will be followed-up for 6 months from the last CB-MSC. Study visits are planned at baseline during CB-MSC administrations, 2 weeks (follow-up [FU]1) and 6 weeks (FU2) after the last infusion, and then every 6 weeks. During follow-up, the patients undergo a physical examination (including measurement of height, weight and blood pressure) and laboratory evaluations (urinary protein:urinary creatinine ratio, complete blood count, kidney function, plasma proteins, liver function, triglycerides and cholesterol). In addition, a blood sample is taken for regulatory T lymphocyte quantification, a marker of clinical response to the infusions.
详细描述
Background:
Nephrotic Syndrome (NS) is a rare disease characterized by nephrotic-range proteinuria and the need for steroid treatment. About 50% of children will become frequent relapsers (FRNS) or steroid dependent (SDNS), requiring higher doses of steroids or other immunosuppressive drugs for many years, sometimes up to adulthood. Strong evidence suggests that Idiopathic nephrotic syndrome (INS), at least in the steroid-sensitive forms, has an immune pathogenesis.
Mesenchymal Stromal Cells (MSC) are multipotent non-hematopoietic stem cells that produce an immunomodulatory activity in-vitro and in-vivo. For this reason, we postulated that SDNS patients could benefit with treatment with MSC.
Objectives:
The main goal of the present study is to assess whether CB-MSCs have the capacity to regulate the immunologic mechanisms involved in the pathogenesis of NS allowing for a reduction or suspension of chronic immunosuppressive treatment in SDNS children. The primary objective is to evaluate whether CB-MSC therapy is able to prevent NS recurrence for at least 6 months after complete withdrawal of immunosuppressive treatment in children with SDNS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 3 and 18 years;
- •Clinical diagnosis of SDNS;
- •Disease remission maintained by chronic therapy (at least 6 months) with either:
- •Use of a combination of 2 or more immunosuppressive drugs
- •use of 1 of the calcineurin inhibitors (Cyclosporin or Tacrolimus);
- •Absence of proteinuria (PrU/CrU < 0.2 mg/mg) for at least 1 month;
- •eGFR greater than or equal to 70 ml/min/1.73 m^2;
- •Written informed consent from parents or guardians and the child when possible
排除标准
- •Age < 3 years or > 19 years;
- •Resistant/refractory NS;
- •Presence of genetic mutations associated with NS;
- •eGFR less than 70 ml/min/1.73m2;
- •Thrombophilic condition;
- •Pregnancy or lactating;
- •Evidence of an uncooperative attitude;
- •Any evidence that the patient will be unable to complete the trial follow-up.
结局指标
主要结局
The percentage of patients without nephrotic syndrome recurrence after complete withdrawal of immunosuppressive treatment for at least 6 months
时间窗: 6 months following completion of the intervention
The percentage of patients without nephrotic-range proteinuria as measured by the urinary protein to urinary creatinine ratio (uPr/uCr\<2) 6 months after completing the intervention
次要结局
- The time to recurrence of nephrotic syndrome(Within 6 months from the completion of the intervention)
- The percentage of adverse events(6 months following completion of the intervention)
- The dose of immunosuppressive therapy to prevent further NS relapses(6 months following completion of the intervention)
- The percentage of participants achieving a reduction in the immunosuppressive therapy(6 months following completion of the intervention)
- Reported Quality of Life(6 months following completion of the intervention)
研究者
Giovanni Montini
Professor
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico