Long-term Follow-up of Participants With Cerebral Adrenoleukodystrophy Who Were Treated With Lenti-D Drug Product

Study Overview
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Brief Summary
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This is a multi-center, long-term safety and efficacy follow-up study for participants with cerebral adrenoleukodystrophy (CALD) who have received Lenti-D Drug Product (eli-cel) in a parent clinical study. After completing a parent clinical study (approximately 2 years), eligible participants will be followed for an additional 13 years for a total of 15 years post-drug product infusion. No investigational drug product will be administered in this study.

Official Title
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Long-term Follow-up of Subjects With Cerebral Adrenoleukodystrophy Who Were Treated With Lenti-D Drug Product

Conditions
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Cerebral Adrenoleukodystrophy (CALD), Adrenoleukodystrophy (ALD), X-Linked Adrenoleukodystrophy (X-ALD)

Intervention / Treatment
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* Genetic: Lenti-D Drug Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent for this study by the participant or participant's parent(s)/ legal guardian(s) and written informed assent by participant, if applicable Have received eli-cel in a parent clinical study Exclusion Criteria: There are no exclusion criteria for this study

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Lenti-D Drug Product<br>Participants who have received Lenti-D Drug Product in a parent clinical study (bluebird bio-sponsored clinical trial) and who meet the eligibility criteria for the study LTF-304 will be followed in this observation study for 13 years (for a total of 15 years of follow-up after drug product infusion in the parent study). | Genetic: Lenti-D Drug Product<br>* Vector copy number (VCN) measurement, safety evaluations, disease-specific assessments, and assessments to monitor for long-term complications of autologous transplant.<br>* Other names: eli-cel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major functional disability (MFD)-free survival | The MFDs are loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, complete loss of voluntary movement. | 15 years post-drug-product infusion | 
| Number of participants with malignancies |  | 15 years post-drug-product infusion | 
| Number of participants who experience graft versus host disease (GVHD) |  | 15 years post-drug-product infusion | 
| Number of participants with immune-related adverse events (AEs) |  | 15 years post-drug-product infusion | 
| Number of participants with new or worsening hematologic disorders |  | 15 years post-drug-product infusion | 
| Number of participants with new or worsening neurologic disorders |  | 15 years post-drug-product infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who undergo subsequent stem cell transplantation |  | 15 years post-drug-product infusion | 
| Change from baseline in neurological function score (NFS) | The NFS is a 25-point score used to evaluate the severity of gross neurologic dysfunction in CALD by scoring 15 symptoms (functional domains) across 6 categories. Listed here are the 15 symptoms followed by their maximal score out of 25 points: a) Hearing / auditory processing problems-1, b) Aphasia / apraxia-1, c) Loss of communication-3, d) Vision impairment /field cut-1, e) Cortical blindness-2, f) Swallowing / other central nervous system (CNS) dysfunctions-2, g) Tube feeding-2, h) Running difficulties / hyperreflexia-1, i) Walking difficulties / spasticity / spastic gait (no assistance)-1, j) Spastic gait (needs assistance)-2, k) Wheelchair dependence-2, l) Complete loss of voluntary movement-3, m) Episodes of incontinence -1, n) Total incontinence-2, o) Nonfebrile seizures-1. A score of 0 denotes absence of clinical signs of cerebral disease. Maximal signs within a domain score the total of all grades within that domain. | 15 years post-drug-product infusion | 
| Number of participants without gadolinium enhancement (GdE) status on magnetic resonance imaging (MRI) | GdE status means participants who will report GdE negative (-) or positive (+). | 15 years post-drug-product infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adrenoleukodystrophy, X-linked Adrenoleukodystrophy, Hematopoietic Stem Cells