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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-513904-33-00 | EU Trial (CTIS) Number | ||
| 2015-002805-13 | EudraCT Number |
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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 (Study ALD-102 or Study ALD-104).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Long-term followup | Participants who have received Lenti-D Drug Product in a parent clinical study (bluebird bio-sponsored clinical studies ALD-102 and ALD-104) and who meet the eligibility criteria for the Study LTF-304 will be followed in this long-term followup study for 13 years (for a total of 15 years of follow-up after drug product infusion in the parent studies). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| No interventional drug product utilized in this follow-up study | Genetic | Participants received a single IV infusion of Lenti-D Drug Product (also known as elivaldogene autotemcel or eli-cel) in either parent Study ALD-102 or ALD-104. The objectives of this long-term follow-up study are to assess long-term safety and efficacy following completion of participation in parent studies. Vector copy number (VCN) measurement, safety evaluations, disease-specific assessments, and assessments to monitor for long-term complications of autologous transplant are conducted in this study. |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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Participants with cerebral adrenoleukodystrophy (CALD) who have received Lenti-D Drug Product in a parent clinical study will be expected to participate in this long-term follow-up study.
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| Name | Affiliation | Role |
|---|---|---|
| Vinod K Prasad, MD, FRCP | bluebird bio, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mattel Children's Hospital-UCLA | Los Angeles | California | 90095 | United States | ||
| Lucile Packard Children's Hospital - Stanford |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39383459 | Derived | Eichler F, Duncan CN, Musolino PL, Lund TC, Gupta AO, De Oliveira S, Thrasher AJ, Aubourg P, Kuhl JS, Loes DJ, Amartino H, Smith N, Folloni Fernandes J, Sevin C, Sankar R, Hussain SA, Gissen P, Dalle JH, Platzbecker U, Downey GF, McNeil E, Demopoulos L, Dietz AC, Thakar HL, Orchard PJ, Williams DA. Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2024 Oct 10;391(14):1302-1312. doi: 10.1056/NEJMoa2400442. | |
| 39383458 |
| Label | URL |
|---|---|
| Parent Study ALD-102 protocol registrations and summary result disclosure | View source |
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bluebird bio is committed to transparency. Appropriately de-identified patient-level datasets and supporting documents may be shared following attainment of applicable marketing approvals associated with this study and consistent with criteria established by bluebird bio and/or industry best practices to maintain the privacy of study participants. For enquiries, please contact us at datasharing@bluebirdbio.com.
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|
| 15 years post-drug-product infusion |
| Number of participants without gadolinium enhancement (GdE) status on magnetic resonance imaging (MRI) | Contrast enhancement (gadolinium enhancement; GdE+) on brain MRI represents a clinically important radiographic biomarker of active neuroinflammatory disease and poor prognosis (in untreated patients). As such, assessment of the number of participants who remained negative for gadolinium enhancement (GdE-) was conducted for this outcome measure. | 15 years post-drug-product infusion |
| Palo Alto |
| California |
| 94304 |
| United States |
| Boston Children's Hospital/Massachusetts General Hospital | Boston | Massachusetts | 02115 | United States |
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Instituto Neurogenia | Caba | Argentina |
| Women's and Children's Hospital | North Adelaide | Australia |
| Hospital das Clínicas da Universidade de São Paulo | São Paulo | 05403-000 | Brazil |
| Hôpital Bicêtre | Le Kremlin-Bicêtre | Cedex | 94275 | France |
| Universitätsklinikum Leipzig AöR | Leipzig | 04103 | Germany |
| Ospedale Pediatrico Bambino Gesù | Rome | 00165 | Italy |
| Prinses Maxima Center | Utrecht | 3584 | Netherlands |
| Royal Free London Hospital | London | England | NW3 2QG | United Kingdom |
| Great Ormond Street Hospital | London | United Kingdom |
| Derived |
| Duncan CN, Bledsoe JR, Grzywacz B, Beckman A, Bonner M, Eichler FS, Kuhl JS, Harris MH, Slauson S, Colvin RA, Prasad VK, Downey GF, Pierciey FJ, Kinney MA, Foos M, Lodaya A, Floro N, Parsons G, Dietz AC, Gupta AO, Orchard PJ, Thakar HL, Williams DA. Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2024 Oct 10;391(14):1287-1301. doi: 10.1056/NEJMoa2405541. |
| Parent Study ALD-104 protocol registrations and summary result disclosure | View source |
| ID | Term |
|---|---|
| D000326 | Adrenoleukodystrophy |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020279 | Hereditary Central Nervous System Demyelinating Diseases |
| D056784 | Leukoencephalopathies |
| D003711 | Demyelinating Diseases |
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D008661 | Metabolism, Inborn Errors |
| D018901 | Peroxisomal Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000309 | Adrenal Insufficiency |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
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