Long-Term Follow-up Study of Participants With Cystinosis Who Received Lentiviral Gene Therapy AVR-RD-04

Study Overview
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Brief Summary
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This is a multinational, long-term follow-up study to assess the long-term safety and durability of AVR-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 AVR-RD-04 infusion.

Detailed Description
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Participants enrolled in a study where the individual received AVR-RD-04 will be offered participation in the AVRO-RD-04-LTF01 study. The Baseline visit for the AVRO-RD-04-LTF01 study will likely coincide with the final visit in the parent study. Participants confirmed eligible for the AVRO-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 AVR-RD-04 treatment will be assessed.

Official Title
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A Long-Term Follow-Up Study of Participants With Cystinosis Who Previously Received AVR-RD-04 (Also Known as CTNS-RD-04)

Conditions
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Cystinosis

Intervention / Treatment
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* Other: Safety and Efficacy Assessments


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Participant must have received AVR-RD-04 (also known as CTNS-RD-04) in a preceding study Exclusion Criteria: • Participant is currently enrolled in an AVRO-RD-04 treatment study. Participants who have either completed, withdrawn, or prematurely discontinued participation for any reason at any time after receiving AVR RD-04 are eligible for AVRO RD 04 LTF01 study participation.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinically significant AEs and 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 
| Incidence of anti-cystinosin antibodies as assessed by immunogenicity testing |  | Baseline to Year 15 post gene therapy | 
| Change from Baseline in Health Survey questionnaire as assessed by (SF-36) scores |  | Baseline to Year 15 post gene therapy | 
| Change from Baseline in Health Survey questionnaire as assessed by EuroQol EQ-5D-5L scores |  | Baseline to Year 15 post gene therapy | 
| Change from Baseline in Treatment Burden as assessed by Burden of Treatment questionnaire (TBQ) scores |  | Baseline to Year 15 post gene therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystinosis Disease, Cell therapy, Gene therapy, Long-term follow-up