Clinical trial NCT06910813: DFT383 in Pediatric Participants With Nephropathic Cystinosis
Official title: An Open-label, Multi-center, Phase I/II Study to Assess Safety, Tolerability and Efficacy of DFT383 in Pediatric Participants With Nephropathic Cystinosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Nephropathic Cystinosis
Keywords: Cystinosis
Nephropathic cystinosis
Lysosomal storage disorder
CTNS gene
DFT383
Cellular gene therapy
Cysteamine
Renal Fanconi syndrome
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2025-04-04
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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.

Primary outcomes:
measure: Incidence of Adverse events (Cohort 1)
timeFrame: Up to 32 months
measure: Number of participants with Hematological reconstitution (Cohort 1)
timeFrame: 42 days post DFT infusion
measure: Proportion of participants with reversal of renal Fanconi syndrome (RFS)
timeFrame: Up to 32 months
Secondary outcomes:
measure: Health-related quality of life (HRQOL)
timeFrame: Up to 32 months
measure: Time from infusion to reversal of RFS
timeFrame: Up to 32 months
measure: Duration of reversal of RFS
timeFrame: Up to 32 months
measure: Change from baseline on urine protein to creatinine ratio (UPr/CR)
timeFrame: Up to 27 months
measure: Change from baseline on urine amino acids
timeFrame: Up to 27 months
measure: Change from baseline on urinary glucose to creatinine ratio
timeFrame: Up to 27 months
measure: Change from baseline on tubular maximum reabsorption of Phosphate/Glomerular Filtration Rate ratio (TmP/GFR)
timeFrame: Up to 27 months
measure: Change from baseline on urine retinol-binding protein/creatinine ratio (RBP/Cr)
timeFrame: Up to 27 months
measure: Number of participants with improvement of proximal tubular function
timeFrame: Up to 27 months
measure: Number of participants independent from cysteamine
timeFrame: 24 months
measure: Corneal cystine crystal content
timeFrame: Up to 27 months
measure: White blood cell cystine levels
timeFrame: Up to 27 months
measure: Number of participants with clinically significant changes in Vital signs, physical/neurological examinations, laboratories, and ECG
timeFrame: Up to 32 months
measure: Number of participants with presence/emergence of replication-competent lentivirus (Cohort 1)
timeFrame: Up to 27 months
measure: Number of participants with Malignancy (Cohort 1)
timeFrame: 24 months
measure: Time to hematological reconstitution (Cohort 1)
timeFrame: 42 days post infusion
measure: Incidence of Adverse Events (Cohort 0)
timeFrame: 24 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University School of Medicine-Children's Healthcare of Atlanta (recuiting Cohort 0)
state: Georgia
Study officials:
References: