DFT383 in Pediatric Participants With Nephropathic Cystinosis

Phase 1

Recruiting

• Conditions: Nephropathic Cystinosis

• Registration Number: NCT06910813
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

An open-label, multi-center, phase I/II study to assess the safety, tolerability and efficacy of DFT383 in pediatric participants with nephropathic cystinosis.

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. 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) treated with Standard of care (SoC). The study is not randomized and Cohort 0 aims to collect prospective and concurrent data in this rare disease.

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. The study consists of participants receiving DFT383 in Cohort 1 and Standard of Care (SoC) in Cohort 0. 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 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.

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 Timeline

• Study First Submitted: 2025-03-17
• Study First Submitted QC: 2025-03-27
• Status Verified: 2025-04
• Study First Posted: 2025-04-04
• Study Start: 2025-04-30
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-07
• Primary Completion: 2030-08-26
• Study Completion: 2030-08-26

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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 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. Preserved kidney function (eGFR ≥ 90mL/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 criteria only apply to Cohort 1 only as they are important for procedures related to DFT383 treatment:

1. Indomethacin within 2 weeks prior to Screening

Other protocol-defined inclusion/exclusion criteria may apply.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse events (Cohort 1)	Up to 32 months	Number and proportion of participants with adverse events (AEs) and serious adverse events (SAEs)
Number of participants with Hematological reconstitution (Cohort 1)	42 days post DFT infusion	Hematological reconstitution by Day 42 post-DFT383 infusion
Proportion of participants with reversal of renal Fanconi syndrome (RFS)	Up to 32 months	Proportion of participants with reversal of renal Fanconi syndrome (RFS)

Secondary Outcome Measures

Name	Time	Method
Health-related quality of life (HRQOL)	Up to 32 months	Health-related quality of life (HRQOL) as measured by QUALIFY (cystinosis-specific PRO)- Currently under development
Time from infusion to reversal of RFS	Up to 32 months	Time from infusion to reversal of renal Fanconi syndrome (RFS)
Duration of reversal of RFS	Up to 32 months	Duration of reversal of renal Fanconi syndrome (RFS)
Change from baseline on urine protein to creatinine ratio (UPr/CR)	Up to 27 months	Change from baseline on urine protein to creatinine ratio (UPr/CR)
Change from baseline on urine amino acids	Up to 27 months	Change from baseline on urine amino acids
Change from baseline on urinary glucose to creatinine ratio	Up to 27 months	Change from baseline on urinary glucose to creatinine ratio
Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio (TmP/GFR)	Up to 27 months	Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio
Change from baseline on urine retinol-binding protein/creatinine ratio (RBP/Cr)	Up to 27 months	Change from baseline on urine retinol-binding protein/creatinine ratio
Number of participants with improvement of proximal tubular function	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.
Number of participants independent from cysteamine	24 months	Independence from oral and ophthalmic cysteamine
Corneal cystine crystal content	Up to 27 months	Corneal crystal content by anterior segment optical coherence tomography (AS-OCT)
White blood cell cystine levels	Up to 27 months	White blood cell cystine levels
Number of participants with clinically significant changes in Vital signs, physical/neurological examinations, laboratories, and ECG	Up to 32 months	Vital signs, physical/neurological examinations, laboratories (eg., chemistry, hematology, liver function tests), and ECG
Number of participants with presence/emergence of replication-competent lentivirus (Cohort 1)	Up to 27 months	Number of participants with presence/emergence of replication-competent lentivirus
Number of participants with Malignancy (Cohort 1)	24 months	Number of participants with Malignancy
Time to hematological reconstitution (Cohort 1)	42 days post infusion	Time to hematological reconstitution
Incidence of Adverse Events (Cohort 0)	24 months	Number and proportion of participants with adverse events (AEs) and serious adverse events (SAEs)

Trial Locations

Locations (1)

Emory University School of Medicine-Children's Healthcare of Atlanta (recuiting Cohort 0); 🇺🇸 Atlanta, Georgia, United States