An Open-label, Multi-center, Phase I/II Study to Assess Safety, Tolerability and Efficacy of DFT383 in Pediatric Participants With Nephropathic Cystinosis, Followed by a Long-term Extension Phase
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 6
- 主要终点
- Core Phase - Proportion of participants with reversal of renal Fanconi syndrome (RFS)
研究概览
简要总结
An open-label, multi-center, phase I/II study to assess the safety, tolerability and efficacy of DFT383 in pediatric participants with nephropathic cystinosis, followed by a long-term extension phase.
The purpose of this clinical study is to assess safety, tolerability, and efficacy of DFT383 in participants aged 2 to 5 years with nephropathic cystinosis. The study consists of a Core Phase and a long-term Extension Phase. DFT383 is a cellular gene therapy.
This study includes an active arm (Cohort 1) of participants treated with study treatment DFT383 and a concurrent reference arm (Cohort 0). Participants in Cohort 0 will not receive study treatment and will only participate in the Core Phase of the study. The study is not randomized and Cohort 0 aims to collect prospective and concurrent data in this rare disease.
详细描述
This study is an open-label, multi-center, phase I/II study to assess the safety, tolerability, and efficacy of DFT383 in participants aged 2 to 5 years with nephropathic cystinosis, followed by a long-term extension phase.
The study includes two Treatment Groups (Cohort 1 and Cohort 0) and consists of a Core Phase and a long-term Extension Phase.
Participants in Cohort 1 will receive DFT383 and participate in both the Core and Extension Phase. Participants in Cohort 0 will not receive study treatment and will participate in the Core Phase only.
The two cohorts will be run in parallel. Investigational sites may participate in one or both cohorts.
Cohort 1 Approximately 15 participants will receive treatment with DFT383 in 3 (sub) cohorts (1A, 1B and 1C) dosed in a staggered approach. The total study duration for a participant in Cohort 1 will be up to 32 months in the core phase and up to 13 years for the long-term extension phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants eligible for inclusion in this study must meet all the following criteria:
- •Informed consent in writing from parent(s) or legal guardian(s) must be provided
- •2 to 5 years of age (including 5 years and 364 days old) at Screening
- •Weight-for-stature is ≥ the third percentile, and is ≥ 10 kg
- •Oral cysteamine therapy for at least 6 months
- •Historic clinical diagnosis of nephropathic cystinosis
- •Laboratory evidence of of renal fanconi syndrome (RFS)
- •Relatively preserved kidney function (eGFR ≥ 60mL/min/1.73m2)
- •Received all age-appropriate vaccinations
排除标准
- •for Cohort 1 and 0
- •A history of kidney transplantation
- •A prior or planned bone marrow or stem cell transplantation or prior treatment with gene therapy
- •History of malignancy
- •A severe or uncontrolled medical disorder
- •Major surgery within 90 days
- •Additional Key exclusion criteria for Cohort 1 - The following exclusion criterion applies to Cohort 1 only as it is related to DFT383 treatment:
- •1. Indomethacin within 2 weeks prior to Screening
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Cohort 0 (SoC)
No study treatment, will continue with standard of care (cysteamine).
Cohort 1 (DFT383)
Treatment with DFT383
干预措施: DFT383 (Genetic)
结局指标
主要结局
Core Phase - Proportion of participants with reversal of renal Fanconi syndrome (RFS)
时间窗: Up to 32 months
Proportion of participants with reversal of renal Fanconi syndrome (RFS)
Core Phase - Incidence of adverse events (Cohort 1)
时间窗: Up to 32 months
Number and proportion of participants with adverse events (AEs) and serious adverse events (SAEs)
Core Phase - Number of participants with hematological reconstitution (Cohort 1)
时间窗: 42 days post DFT infusion
Hematological reconstitution by Day 42 post-DFT383 infusion
次要结局
- Core Phase - Time to platelet engraftment (Cohort 1)(Up to 24 months)
- Core Phase - Time to hematological reconstitution (Cohort 1)(Up to 24 months)
- Core Phase - Number of participants with malignancy (Cohort 1)(Up to 27 months)
- Core Phase - Number of participants independent from cysteamine(up to 24 months)
- Core Phase - Number of participants with presence/emergence of replication-competent lentivirus (Cohort 1)(Up to 27 months)
- Core Phase - Health-related quality of life (HRQOL)(Up to 32 months)
- Core Phase - Time from infusion to reversal of RFS (Cohort 1)(Up to 24 months)
- Core Phase - Time from screening to reversal of RFS (Cohort 0)(Up to 24 months)
- Core Phase - Duration of reversal of RFS(Up to 24 months)
- Core Phase - Change from baseline on urine protein to creatinine ratio (UPr/CR)(Up to 27 months)
- Core Phase - Change from baseline on urine amino acids(Up to 27 months)
- Core Phase - Change from baseline on urinary glucose to creatinine ratio(Up to 27 months)
- Core Phase - Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio (TmP/GFR)(Up to 27 months)
- Core Phase - Change from baseline on urine retinol-binding protein/creatinine ratio (RBP/Cr)(Up to 27 months)
- Core Phase - Number of participants with improvement of proximal tubular function(Up to 27 months)
- Core Phase - Corneal cystine crystal content(Up to 27 months)
- Core Phase - Number of participants with clinically significant changes in vital signs, physical examinations, laboratories, and ECG (Cohort 1)(Up to 27 months)
- Core Phase - Incidence of Adverse Events (Cohort 0)(up to 24 months)
- Extension Phase Primary Objective - Incidence of Adverse events (Cohort 1)(Up to 15 years and 8 months)
- Extension Phase - Number of participants with malignancy (Cohort 1)(Up to 15 years and 3 months)
- Extension Phase - Number of participants with presence/emergence of replication-competent lentivirus (Cohort 1)(Up to 15 years and 3 months)
- Extension Phase - Number of participants with clinically significant changes in vital signs, physical examinations, laboratories, and ECG (Cohort 1)(Up to 15 years and 3 months)
- Extension Phase - Change from baseline on urine protein to creatinine ratio (UPr/CR) (Cohort 1)(Up to 15 years and 3 months)
- Extension Phase - Change from baseline on urine amino acids (Cohort 1)(Up to 15 years and 3 months)
- Extension Phase - Change from baseline on urinary glucose to creatinine ratio (Cohort 1)(Up to 15 years and 3 months)
- Extension Phase - Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio (TmP/GFR) (Cohort 1)(Up to 15 years and 3 months)
- Extension Phase - Change from baseline on urine retinol-binding protein/creatinine ratio (RBP/Cr) (Cohort 1)(Up to 15 years and 3 months)
- Extension Phase - Duration of reversal of RFS (Cohort 1)(Up to 15 years)
- Extension Phase - Number of participants with kidney failure (Cohort 1)(Up to 15 years)
- Extension Phase - Number of participants independent from cysteamine (Cohort 1)(Up to 15 years)
- Extension Phase - Corneal cystine crystal content (Cohort 1)(Up to 15 years and 3 months)
- Extension Phase - Health-related quality of life (HRQOL) (Cohort 1)(Up to 15 years and 8 months)