Clinical trial NCT05146830: A Long-Term Follow-Up Study of Participants With Cystinosis Who Previously Received CTNS-RD-04
Official title: A Long-Term Follow-Up Study of Participants With Cystinosis Who Previously Received CTNS-RD-04
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Cystinosis
Keywords: Cystinosis Disease
Cell therapy
Gene therapy
Long-term follow-up
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: California Institute for Regenerative Medicine (CIRM)
name: Cystinosis Research Foundation
name: Novartis Pharmaceuticals
First posted: 2021-12-07
Enrollment: 50
Sex: ALL
Minimum age (years): 14
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants who received CTNS-RD-04 and agree to comply with the study visit schedule and procedures.

Brief summary: This is a multinational, long-term follow-up study to assess the long-term safety and durability of CTNS-RD-04 treatment in participants who received a single dose administration of lentiviral gene therapy. No investigational product will be administered in this study. Participants will continue periodic safety and efficacy assessments in this long-term follow-up study up to 15 years from the initial date of CTNS-RD-04 infusion.

Detailed description: 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.

Eligibility criteria: 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 Participants who have either completed, withdrawn, or prematurely discontinued participation for any reason at any time after receiving CTNS-RD-04 are eligible for CTNS RD 04 LTF01 study participation.

Primary outcomes:
measure: Incidence of clinically significant Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline to Year 15 post gene therapy
measure: Number of participants with clinically relevant abnormalities, as assessed by vital sign (heart rate, pulse rate, and temperature)
timeFrame: Baseline to Year 15 post gene therapy
measure: Number of participants with clinically relevant abnormalities, as assessed by clinical laboratory tests (chemistry and hematology)
timeFrame: Baseline to Year 15 post gene therapy
measure: Number of participants with clinically relevant abnormalities, as assessed by by electrocardiograms (ECGs) (rate, rhythm, intervals)
timeFrame: Baseline to Year 15 post gene therapy
Secondary outcomes:
measure: Change from baseline in Corneal cystine crystal score (CCCS) as assessed by in vivo confocal microscopy (IVCM)
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in Renal glomerular and tubular functions measured by glomerular filtration rate (GFR)
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in vision function as assessed by ophthalmology exams
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in grip strength measured by dynamometry
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in respiratory function measured by spirometry
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in bone density assessed by dual-energy X-ray absorptiometry (DEXA)
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in muscle mass assessed by dual-energy X-ray absorptiometry (DEXA)
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in Endocrine function measured by fasting glucose, thyroid function, and gonadotropin levels
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in neurological function assessed by neurological exam (mental status, coordination, sensory, reflexes, and visual motor integration)
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in psychometric function assessed by neurological exam (memory, oromotor function, intelligence quotient (IQ))
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in pill/injection count related to cystinosis treatment
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in Cystinosin (CTNS) as assessed by quantitative Polymerase Chain Reaction (qPCR)
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in mean Vector Copy Number (VCN) as assessed by quantitative Polymerase Chain Reaction (qPCR)
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in Cystine levels in leukocytes measured by mass spectrometry
timeFrame: Baseline to Year 15 post gene therapy
measure: Change from baseline in ovarian reserve and menstrual cycle as assessed by anti-Müllerian hormone (AMH) and gynecology exams
timeFrame: Baseline to Year 15 post gene therapy
measure: Change in male reproductive potential as assessed by urology exams (sperm count, motility, and morphology)
timeFrame: Baseline to Year 15 post gene therapy
measure: Absence of Replication Competent Lentivirus (RCL) as assessed by Elisa assay
timeFrame: Baseline to Year 15 post gene therapy
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
Study officials:
affiliation: University of California, San Diego
name: Stephanie Cherqui, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.