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NCT Number: NCT06910813

DFT383 in Pediatric Participants With Nephropathic Cystinosis

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.

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Key information

Conditions

Nephropathic Cystinosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cystinosis Fanconi Syndrome Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Kidney Diseases Lysosomal Storage Diseases Male Urogenital Diseases Metabolic Diseases Metabolism, Inborn Errors Nutritional and Metabolic Diseases Renal Tubular Transport, Inborn Errors Urogenital Diseases Urologic Diseases

Age range

2 year–5 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University of California at San Diego - Rady Children's Hospital, San Diego, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

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:

  • Indomethacin within 2 weeks prior to Screening

Other protocol-defined inclusion/exclusion criteria may apply.

Treatment and study plan

DFT383

Genetic

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

Primary outcomes

  1. Core Phase - Incidence of adverse events (Cohort 1)

    Time frame: Up to 32 months

    Number and proportion of participants with adverse events (AEs) and serious adverse events (SAEs)

  2. Core Phase - Number of participants with hematological reconstitution (Cohort 1)

    Time frame: 42 days post DFT infusion

    Hematological reconstitution by Day 42 post-DFT383 infusion

  3. Core Phase - Proportion of participants with reversal of renal Fanconi syndrome (RFS)

    Time frame: Up to 32 months

    Proportion of participants with reversal of renal Fanconi syndrome (RFS)

Secondary outcomes

  1. Core Phase - Number of participants independent from cysteamine

    Time frame: up to 24 months

    Independence from oral and ophthalmic cysteamine

  2. Core Phase - Health-related quality of life (HRQOL)

    Time frame: Up to 32 months

    Health-related quality of life (HRQOL) as measured by QUALIFY (cystinosis-specific PRO)- Currently under development

  3. Core Phase - Time from infusion to reversal of RFS (Cohort 1)

    Time frame: Up to 24 months

    Time from infusion to reversal of renal Fanconi syndrome (RFS)

  4. Core Phase - Time from screening to reversal of RFS (Cohort 0)

    Time frame: Up to 24 months

    Time from screening to reversal of renal Fanconi syndrome (RFS)

  5. Core Phase - Duration of reversal of RFS

    Time frame: Up to 24 months

    Duration of reversal of renal Fanconi syndrome (RFS)

  6. Core Phase - Change from baseline on urine protein to creatinine ratio (UPr/CR)

    Time frame: Up to 27 months

    Change from baseline on urine protein to creatinine ratio (UPr/CR)

  7. Core Phase - Change from baseline on urine amino acids

    Time frame: Up to 27 months

    Change from baseline on urine amino acids

  8. Core Phase - Change from baseline on urinary glucose to creatinine ratio

    Time frame: Up to 27 months

    Change from baseline on urinary glucose to creatinine ratio

  9. Core Phase - Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio (TmP/GFR)

    Time frame: Up to 27 months

    Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio

  10. Core Phase - Change from baseline on urine retinol-binding protein/creatinine ratio (RBP/Cr)

    Time frame: Up to 27 months

    Change from baseline on urine retinol-binding protein/creatinine ratio

  11. Core Phase - Number of participants with improvement of proximal tubular function

    Time frame: Up to 27 months

    Improvement of proximal tubular function as defined by 2-fold change from Baseline of at least 4 out of 5 RFS parameters (urine protein to creatinine ratio, urine amino acids, urinary glucose to creatinine ratio, tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate, urine retinol-binding protein/creatinine ratio). Improvement will also be considered if the change from Baseline is less than 2-fold but the value falls within the definition for normalization.

  12. Core Phase - Corneal cystine crystal content

    Time frame: Up to 27 months

    Corneal crystal content by anterior segment optical coherence tomography (AS-OCT)

  13. Core Phase - Number of participants with clinically significant changes in vital signs, physical examinations, laboratories, and ECG (Cohort 1)

    Time frame: Up to 27 months

    Vital signs, physical examinations, laboratories (eg., chemistry, hematology, liver function tests), and ECG

  14. Core Phase - Number of participants with presence/emergence of replication-competent lentivirus (Cohort 1)

    Time frame: Up to 27 months

    Number of participants with presence/emergence of replication-competent lentivirus

  15. Core Phase - Number of participants with malignancy (Cohort 1)

    Time frame: Up to 27 months

    Number of participants with malignancy

  16. Core Phase - Time to hematological reconstitution (Cohort 1)

    Time frame: Up to 24 months

    Time to hematological reconstitution

  17. Core Phase - Time to platelet engraftment (Cohort 1)

    Time frame: Up to 24 months

    Time to platelet engraftment

  18. Core Phase - Incidence of Adverse Events (Cohort 0)

    Time frame: up to 24 months

    Number and proportion of participants with adverse events (AEs) and serious adverse events (SAEs)

  19. Extension Phase Primary Objective - Incidence of Adverse events (Cohort 1)

    Time frame: Up to 15 years and 8 months

    Number and proportion of participants with adverse events (AEs) and serious adverse events (SAEs)

  20. Extension Phase - Number of participants with malignancy (Cohort 1)

    Time frame: Up to 15 years and 3 months

    Number of participants with malignancy

  21. Extension Phase - Number of participants with presence/emergence of replication-competent lentivirus (Cohort 1)

    Time frame: Up to 15 years and 3 months

    Number of participants with presence/emergence of replication-competent lentivirus

  22. Extension Phase - Number of participants with clinically significant changes in vital signs, physical examinations, laboratories, and ECG (Cohort 1)

    Time frame: Up to 15 years and 3 months

    Vital signs, physical examinations, laboratories (eg., chemistry, hematology, liver function tests), and ECG

  23. Extension Phase - Change from baseline on urine protein to creatinine ratio (UPr/CR) (Cohort 1)

    Time frame: Up to 15 years and 3 months

    Change from baseline on urine protein to creatinine ratio (UPr/CR)

  24. Extension Phase - Change from baseline on urine amino acids (Cohort 1)

    Time frame: Up to 15 years and 3 months

    Change from baseline on urine amino acids

  25. Extension Phase - Change from baseline on urinary glucose to creatinine ratio (Cohort 1)

    Time frame: Up to 15 years and 3 months

    Change from baseline on urinary glucose to creatinine ratio

  26. Extension Phase - Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio (TmP/GFR) (Cohort 1)

    Time frame: Up to 15 years and 3 months

    Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio

  27. Extension Phase - Change from baseline on urine retinol-binding protein/creatinine ratio (RBP/Cr) (Cohort 1)

    Time frame: Up to 15 years and 3 months

    Change from baseline on urine retinol-binding protein/creatinine ratio

  28. Extension Phase - Duration of reversal of RFS (Cohort 1)

    Time frame: Up to 15 years

    Duration of reversal of renal Fanconi syndrome (RFS)

  29. Extension Phase - Number of participants with kidney failure (Cohort 1)

    Time frame: Up to 15 years

    Number of participants with kidney failure

  30. Extension Phase - Number of participants independent from cysteamine (Cohort 1)

    Time frame: Up to 15 years

    Independence from oral and ophthalmic cysteamine

  31. Extension Phase - Corneal cystine crystal content (Cohort 1)

    Time frame: Up to 15 years and 3 months

    Corneal crystal content by anterior segment optical coherence tomography (AS-OCT)

  32. Extension Phase - Health-related quality of life (HRQOL) (Cohort 1)

    Time frame: Up to 15 years and 8 months

    Health-related quality of life (HRQOL) as measured by QUALIFY (cystinosis-specific PRO)- Currently under development

Study contacts

Contact information is provided by the study sponsor or research team.

Novartis Pharmaceuticals

CONTACT

[email protected]

1-888-669-6682

Novartis Pharmaceuticals

CONTACT

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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

Acronym: CYStem

Important dates

Study start
2025
Primary completion
2031
Study completion
2044
First posted
Apr 4, 2025
Registry last updated
May 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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