DFT383 in Pediatric Participants With Nephropathic Cystinosis

Phase 2RecruitingNCT06910813

Novartis Pharmaceuticals30 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Eligibility

Sex: ALLMin age: 2 YearsMax age: 5 Years

Medical Language ↔ Plain English

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.

Locations (4)

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

San Diego, California, United States

RECRUITING

Stanford University - Stanford Children's Health

Stanford, California, United States

RECRUITING

Emory University School of Medicine - Children's Healthcare of Atlanta (recuiting Cohort 0)

Atlanta, Georgia, United States

RECRUITING

Baylor College of Medicine - Texas Children's Hospital (recuiting Cohort 0)

Houston, Texas, United States

RECRUITING

Outcomes

Primary Outcomes

Core Phase - Incidence of adverse events (Cohort 1)

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

Time frame: Up to 32 months

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

Hematological reconstitution by Day 42 post-DFT383 infusion

Time frame: 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)

Time frame: Up to 32 months

Secondary Outcomes

Core Phase - Number of participants independent from cysteamine

Independence from oral and ophthalmic cysteamine

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: Up to 24 months

Core Phase - Duration of reversal of RFS

Duration of reversal of renal Fanconi syndrome (RFS)

Time frame: 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)

Time frame: Up to 27 months

Core Phase - Change from baseline on urine amino acids

Change from baseline on urine amino acids

Time frame: Up to 27 months

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

Change from baseline on urinary glucose to creatinine ratio

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: Up to 27 months

Core Phase - Corneal cystine crystal content

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

Time frame: 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

Time frame: 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

Time frame: Up to 27 months

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

Number of participants with malignancy

Time frame: Up to 27 months

Core Phase - Time to hematological reconstitution (Cohort 1)

Time to hematological reconstitution

Time frame: Up to 24 months

Core Phase - Time to platelet engraftment (Cohort 1)

Time to platelet engraftment

Time frame: 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)

Time frame: 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)

Time frame: Up to 15 years and 8 months

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

Number of participants with malignancy

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Up to 15 years and 3 months

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

Duration of reversal of renal Fanconi syndrome (RFS)

Time frame: Up to 15 years

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

Number of participants with kidney failure

Time frame: Up to 15 years

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

Independence from oral and ophthalmic cysteamine

Time frame: Up to 15 years

Extension Phase - Corneal cystine crystal content (Cohort 1)

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

Time frame: 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

Time frame: Up to 15 years and 8 months

DFT383 in Pediatric Participants With Nephropathic Cystinosis

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts