DFT383 in Pediatric Participants With Nephropathic Cystinosis

Официальное название

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

Обзор

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.

Подробное описание

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.

Cohort 0 Approximately 15 participants meeting similar inclusion/exclusion criteria and receiving SoC will be enrolled. The Schedule of Activities will be reduced for this Cohort. This cohort 0 is not a direct control but will provide essential context for interpreting the results observed in the participants receiving DFT383. The total study duration for a participant in Cohort 0 will be up to 24 months.

Вмешательства

• Генная терапия DFT383
  DFT383 is an autologous hematopoietic stem cell (HSC) gene therapy.

Первичные конечные точки

• Core Phase - Incidence of adverse events (Cohort 1) [Срок оценки: Up to 32 months]
• Core Phase - Number of participants with hematological reconstitution (Cohort 1) [Срок оценки: 42 days post DFT infusion]
• Core Phase - Proportion of participants with reversal of renal Fanconi syndrome (RFS) [Срок оценки: Up to 32 months]

Вторичные конечные точки (12)

• Core Phase - Number of participants independent from cysteamine [Срок оценки: up to 24 months]
• Core Phase - Health-related quality of life (HRQOL) [Срок оценки: Up to 32 months]
• Core Phase - Time from infusion to reversal of RFS (Cohort 1) [Срок оценки: Up to 24 months]
• Core Phase - Time from screening to reversal of RFS (Cohort 0) [Срок оценки: Up to 24 months]
• Core Phase - Duration of reversal of RFS [Срок оценки: Up to 24 months]
• Core Phase - Change from baseline on urine protein to creatinine ratio (UPr/CR) [Срок оценки: Up to 27 months]
• Core Phase - Change from baseline on urine amino acids [Срок оценки: Up to 27 months]
• Core Phase - Change from baseline on urinary glucose to creatinine ratio [Срок оценки: Up to 27 months]
• Core Phase - Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio (TmP/GFR) [Срок оценки: Up to 27 months]
• Core Phase - Change from baseline on urine retinol-binding protein/creatinine ratio (RBP/Cr) [Срок оценки: Up to 27 months]
• Core Phase - Number of participants with improvement of proximal tubular function [Срок оценки: Up to 27 months]
• Core Phase - Corneal cystine crystal content [Срок оценки: Up to 27 months]

Критерии участия

Критерии включения

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

Key exclusion Criteria 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 5 центров

• Phoenix Children's Hospital (Recruitng Cohort 0 and 1) — Phoenix
• University of California at San Diego - Rady Children's Hospital — San Diego
• Stanford University - Stanford Children's Health — Stanford
• Emory University School of Medicine - Children's Healthcare of Atlanta (recuiting Cohort 0 — Atlanta
• Baylor College of Medicine - Texas Children's Hospital (recuiting Cohort 0) — Houston

Идентификаторы

NCT: NCT06910813 · CDFT383A12101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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