A Long-Term Follow-Up Study of Participants With Cystinosis Who Previously Received CTNS-RD-04

Participants enrolled in a study where the individual received CTNS-RD-04 will be offered participation in the CTNS-RD-04-LTF01 study. The Baseline visit for the CTNS-RD-04-LTF01 study will likely coincide with the final visit in the parent study. Participants confirmed eligible for the CTNS-RD-04-LTF01 study will be asked to return for study visits at approximately 6-month intervals for the first 4 years and annually thereafter for up to 11 years until a total of 15 years have elapsed during which time continued safety, engraftment, and efficacy of CTNS-RD-04 treatment will be assessed.

• Safety and Efficacy Assessments (Other), also known as Gene Therapy Intervention: Safety evaluations, disease-specific assessments, and other assessments to monitor for long-term complications of gene therapy intervention.

Primary outcomes

• Incidence of clinically significant Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline to Year 15 post gene therapy]
• Number of participants with clinically relevant abnormalities, as assessed by vital sign (heart rate, pulse rate, and temperature) [Baseline to Year 15 post gene therapy]
• Number of participants with clinically relevant abnormalities, as assessed by clinical laboratory tests (chemistry and hematology) [Baseline to Year 15 post gene therapy]
• Number of participants with clinically relevant abnormalities, as assessed by by electrocardiograms (ECGs) (rate, rhythm, intervals) [Baseline to Year 15 post gene therapy]

Secondary outcomes

• Change from baseline in Corneal cystine crystal score (CCCS) as assessed by in vivo confocal microscopy (IVCM) [Baseline to Year 15 post gene therapy]
• Change from baseline in Renal glomerular and tubular functions measured by glomerular filtration rate (GFR) [Baseline to Year 15 post gene therapy]
• Change from baseline in vision function as assessed by ophthalmology exams [Baseline to Year 15 post gene therapy]
• Change from baseline in grip strength measured by dynamometry [Baseline to Year 15 post gene therapy]
• Change from baseline in respiratory function measured by spirometry [Baseline to Year 15 post gene therapy]
• Change from baseline in bone density assessed by dual-energy X-ray absorptiometry (DEXA) [Baseline to Year 15 post gene therapy]
• Change from baseline in muscle mass assessed by dual-energy X-ray absorptiometry (DEXA) [Baseline to Year 15 post gene therapy]
• Change from baseline in Endocrine function measured by fasting glucose, thyroid function, and gonadotropin levels [Baseline to Year 15 post gene therapy]
• Change from baseline in neurological function assessed by neurological exam (mental status, coordination, sensory, reflexes, and visual motor integration) [Baseline to Year 15 post gene therapy]
• Change from baseline in psychometric function assessed by neurological exam (memory, oromotor function, intelligence quotient (IQ)) [Baseline to Year 15 post gene therapy]
• Change from baseline in pill/injection count related to cystinosis treatment [Baseline to Year 15 post gene therapy]
• Change from baseline in Cystinosin (CTNS) as assessed by quantitative Polymerase Chain Reaction (qPCR) [Baseline to Year 15 post gene therapy]
• Change from baseline in mean Vector Copy Number (VCN) as assessed by quantitative Polymerase Chain Reaction (qPCR) [Baseline to Year 15 post gene therapy]
• Change from baseline in Cystine levels in leukocytes measured by mass spectrometry [Baseline to Year 15 post gene therapy]
• Change from baseline in ovarian reserve and menstrual cycle as assessed by anti-Müllerian hormone (AMH) and gynecology exams [Baseline to Year 15 post gene therapy]
• Change in male reproductive potential as assessed by urology exams (sperm count, motility, and morphology) [Baseline to Year 15 post gene therapy]
• Absence of Replication Competent Lentivirus (RCL) as assessed by Elisa assay [Baseline to Year 15 post gene therapy]

Sex: All, ages: 14 Years to 50 Years

Inclusion Criteria:

• Participant must have received CTNS-RD-04 in a preceding study

Exclusion Criteria:

• Participant is currently enrolled in an CTNS-RD-04 treatment study. Participants who have either completed, withdrawn, or prematurely discontinued participation for any reason at any time after receiving CTNS-RD-04 are eligible for CTNS RD 04 LTF01 study participation.

• Results publication: Harrison F, Yeagy BA, Rocca CJ, Kohn DB, Salomon DR, Cherqui S. Hematopoietic stem cell gene therapy for the multisystemic lysosomal storage disorder cystinosis. Mol Ther. 2013 Feb;21(2):433-44. doi: 10.1038/mt.2012.214. Epub 2012 Oct 23. PMID 23089735
• Results publication: Naphade S, Sharma J, Gaide Chevronnay HP, Shook MA, Yeagy BA, Rocca CJ, Ur SN, Lau AJ, Courtoy PJ, Cherqui S. Brief reports: Lysosomal cross-correction by hematopoietic stem cell-derived macrophages via tunneling nanotubes. Stem Cells. 2015 Jan;33(1):301-9. doi: 10.1002/stem.1835. PMID 25186209

• Stephanie Cherqui, PhD, Principal investigator, University of California, San Diego