DFT383 in Pediatric Participants With Nephropathic Cystinosis (CYStem)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Nephropathic Cystinosis
• Intervention / Treatment: Genetic: DFT383

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Recruiting
      • University of California at San Diego - Rady Children's Hospital
      • Contact: Mieko Pretlow; Phone Number: Ext 226010 858-966-1700; Email: mpretlow@rchsd.org
      • Principal Investigator: Nadine Benador nbenador@health.ucsd.edu
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University - Stanford Children's Health
      • Principal Investigator: Alice Bertaina
      • Contact: Research Nurse; Phone Number: 650-725-9032; Email: scgt_clinical_trials_office@lists.stanford.edu
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University School of Medicine - Children's Healthcare of Atlanta (recuiting Cohort 0)
      • Principal Investigator: Laurence (Larry) Greenbaum
      • Contact: Laurence (Larry) Greenbaum; Phone Number: 404-712-6374; Email: lgreen6@emory.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine - Texas Children's Hospital (recuiting Cohort 0)
      • Contact: Ewa Elenberg; Phone Number: 832-824-3800; Email: Email_elenberg@bcm.edu
      • Principal Investigator: Ewa Elenberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Participants eligible for inclusion in this study must meet all the following criteria:

1. Informed consent in writing from parent(s) or legal guardian(s) must be provided
2. 2 to 5 years of age (including 5 years and 364 days old) at Screening
3. Weight-for-stature is ≥ the third percentile, and is ≥ 10 kg
4. Oral cysteamine therapy for at least 6 months
5. Historic clinical diagnosis of nephropathic cystinosis
6. Laboratory evidence of of renal fanconi syndrome (RFS)
7. Relatively preserved kidney function (eGFR ≥ 60mL/min/1.73m2)
8. Received all age-appropriate vaccinations

Key exclusion Criteria for Cohort 1 and 0

1. A history of kidney transplantation
2. A prior or planned bone marrow or stem cell transplantation or prior treatment with gene therapy
3. History of malignancy
4. A severe or uncontrolled medical disorder
5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (DFT383); Treatment with DFT383	Genetic: DFT383; DFT383 is an autologous hematopoietic stem cell (HSC) gene therapy.
No Intervention: Cohort 0 (SoC); No study treatment, will continue with standard of care (cysteamine).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Phase - Incidence of adverse events (Cohort 1)	Number and proportion of participants with adverse events (AEs) and serious adverse events (SAEs)	Up to 32 months
Core Phase - Number of participants with hematological reconstitution (Cohort 1)	Hematological reconstitution by Day 42 post-DFT383 infusion	42 days post DFT infusion
Core Phase - Proportion of participants with reversal of renal Fanconi syndrome (RFS)	Proportion of participants with reversal of renal Fanconi syndrome (RFS)	Up to 32 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Phase - Number of participants independent from cysteamine	Independence from oral and ophthalmic cysteamine	up to 24 months
Core Phase - Health-related quality of life (HRQOL)	Health-related quality of life (HRQOL) as measured by QUALIFY (cystinosis-specific PRO)- Currently under development	Up to 32 months
Core Phase - Time from infusion to reversal of RFS (Cohort 1)	Time from infusion to reversal of renal Fanconi syndrome (RFS)	Up to 24 months
Core Phase - Time from screening to reversal of RFS (Cohort 0)	Time from screening to reversal of renal Fanconi syndrome (RFS)	Up to 24 months
Core Phase - Duration of reversal of RFS	Duration of reversal of renal Fanconi syndrome (RFS)	Up to 24 months
Core Phase - Change from baseline on urine protein to creatinine ratio (UPr/CR)	Change from baseline on urine protein to creatinine ratio (UPr/CR)	Up to 27 months
Core Phase - Change from baseline on urine amino acids	Change from baseline on urine amino acids	Up to 27 months
Core Phase - Change from baseline on urinary glucose to creatinine ratio	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)	Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio	Up to 27 months
Core Phase - Change from baseline on urine retinol-binding protein/creatinine ratio (RBP/Cr)	Change from baseline on urine retinol-binding protein/creatinine ratio	Up to 27 months
Core Phase - Number of participants with improvement of proximal tubular function	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.	Up to 27 months
Core Phase - Corneal cystine crystal content	Corneal crystal content by anterior segment optical coherence tomography (AS-OCT)	Up to 27 months
Core Phase - Number of participants with clinically significant changes in vital signs, physical examinations, laboratories, and ECG (Cohort 1)	Vital signs, physical examinations, laboratories (eg., chemistry, hematology, liver function tests), and ECG	Up to 27 months
Core Phase - Number of participants with presence/emergence of replication-competent lentivirus (Cohort 1)	Number of participants with presence/emergence of replication-competent lentivirus	Up to 27 months
Core Phase - Number of participants with malignancy (Cohort 1)	Number of participants with malignancy	Up to 27 months
Core Phase - Time to hematological reconstitution (Cohort 1)	Time to hematological reconstitution	Up to 24 months
Core Phase - Time to platelet engraftment (Cohort 1)	Time to platelet engraftment	Up to 24 months
Core Phase - Incidence of Adverse Events (Cohort 0)	Number and proportion of participants with adverse events (AEs) and serious adverse events (SAEs)	up to 24 months
Extension Phase Primary Objective - Incidence of Adverse events (Cohort 1)	Number and proportion of participants with adverse events (AEs) and serious adverse events (SAEs)	Up to 15 years and 8 months
Extension Phase - Number of participants with malignancy (Cohort 1)	Number of participants with malignancy	Up to 15 years and 3 months
Extension Phase - Number of participants with presence/emergence of replication-competent lentivirus (Cohort 1)	Number of participants with presence/emergence of replication-competent lentivirus	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)	Vital signs, physical examinations, laboratories (eg., chemistry, hematology, liver function tests), and ECG	Up to 15 years and 3 months
Extension Phase - Change from baseline on urine protein to creatinine ratio (UPr/CR) (Cohort 1)	Change from baseline on urine protein to creatinine ratio (UPr/CR)	Up to 15 years and 3 months
Extension Phase - Change from baseline on urine amino acids (Cohort 1)	Change from baseline on urine amino acids	Up to 15 years and 3 months
Extension Phase - Change from baseline on urinary glucose to creatinine ratio (Cohort 1)	Change from baseline on urinary glucose to creatinine ratio	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)	Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio	Up to 15 years and 3 months
Extension Phase - Change from baseline on urine retinol-binding protein/creatinine ratio (RBP/Cr) (Cohort 1)	Change from baseline on urine retinol-binding protein/creatinine ratio	Up to 15 years and 3 months
Extension Phase - Duration of reversal of RFS (Cohort 1)	Duration of reversal of renal Fanconi syndrome (RFS)	Up to 15 years
Extension Phase - Number of participants with kidney failure (Cohort 1)	Number of participants with kidney failure	Up to 15 years
Extension Phase - Number of participants independent from cysteamine (Cohort 1)	Independence from oral and ophthalmic cysteamine	Up to 15 years
Extension Phase - Corneal cystine crystal content (Cohort 1)	Corneal crystal content by anterior segment optical coherence tomography (AS-OCT)	Up to 15 years and 3 months
Extension Phase - Health-related quality of life (HRQOL) (Cohort 1)	Health-related quality of life (HRQOL) as measured by QUALIFY (cystinosis-specific PRO)- Currently under development	Up to 15 years and 8 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2025
• Primary Completion (Estimated): March 14, 2031
• Study Completion (Estimated): March 14, 2044

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): April 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Lysosomal storage disorder; Cysteamine; Cystinosis; Nephropathic cystinosis; CTNS gene; DFT383; Cellular gene therapy; Renal Fanconi syndrome
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Renal Tubular Transport, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Cystinosis; Fanconi Syndrome; Lysosomal Storage Diseases
• Other Study ID Numbers: CDFT383A12101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No