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.

White blood cell (WBC) cystine levels serve as the primary therapeutic target for monitoring cysteamine treatment in cystinosis, with a goal of \<1.9 nmol ½ cystine/mg protein as measured 5-6 hours post-dose when treated with immediate-release formulation, Cystagon® , or 11-12 hours post-dose when treated with delayed-release formulation, Procysbi®, using UCSD granulocyte assay. Although cysteamine dosing in cystinosis has traditionally been individualized based on WBC cystine levels, the FDA-approved Cystagon® prescribing information now includes an approximate recommended maintenance dose of 1.30 g/m²/day. When this dosing strategy is plotted against body weight, it aligns with the dosing regimen of TTI-0102 that was found effective in mitochondrial diseases, demonstrating a linear relationship between dose and weight. The main objective of this study is to demonstrate that administration of a single dose of 60 ± 5 mg/kg/day of TTI-0102 (\~26 mg/kg cysteamine base equivalent) allows maintenance of WBC cystine at \<1.9 nmol ½ cystine/mg protein over 24 hours as determined by UCSD granulocyte assay.

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to enroll.

Nephropathic Cystinosis (NC) is an orphan inherited autosomal recessive disease characterised as a generalized lysosomal storage disease due to a deficiency of the cystine lysosomal transport protein, cystinosin. Patients with NC usually receive cysteamine. Bone impairment was recently recognized as a late complication of NC, occurring at adolescence or early adulthood. Even though the exact underlying pathophysiology is unclear, at least six hypotheses are discussed, and mainly cysteamine toxicity and/or direct bone effect of the Cystinosin (CTNS) mutation. Because of the potential dramatic impact on quality of life of this novel complication, research should aim to better understand bone disease in NC. The primary objective of this study is to evaluate the action of cysteamine on osteoclastic differentiation and resorption activity of NC patients, depending on the underlying genotype. The Secondary objective is to describe the clinical bone status of NC patients depending on their underlying genotype.