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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cystinosis
• Intervention / Treatment: Other: Safety and Efficacy Assessments

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.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants who received CTNS-RD-04 and agree to comply with the study visit schedule and procedures.

Description

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 Participants who have either completed, withdrawn, or prematurely discontinued participation for any reason at any time after receiving CTNS-RD-04 are eligible for CTNS RD 04 LTF01 study participation.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants with Cystinosis Disease; This is a long-term follow-up study of participants who previously received CTNS-RD-04 (single dose administration). No investigational product will be administered in this study.	Other: Safety and Efficacy Assessments; Safety evaluations, disease-specific assessments, and other assessments to monitor for long-term complications of gene therapy intervention.; Other Names: Gene Therapy Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
Incidence of clinically significant Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline to Year 15 post gene therapy

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Stephanie Cherqui
• Collaborators: Novartis Pharmaceuticals; California Institute for Regenerative Medicine (CIRM); Cystinosis Research Foundation
• Investigators: Principal Investigator: Stephanie Cherqui, PhD, University of California, San Diego

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2022
• Primary Completion (Estimated): November 30, 2036
• Study Completion (Estimated): November 30, 2036

Study Registration Dates

• First Submitted: October 28, 2021
• First Submitted That Met QC Criteria: November 23, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 1, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Cell therapy; Gene therapy; Long-term follow-up; Cystinosis Disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Cystinosis
• Other Study ID Numbers: CTNS-RD-04-LTFU01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: To keep consistent with current treatment listing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No