A Clinical Study to Assess the Efficacy and Safety of Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy (CALD)
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|ClinicalTrials.gov Identifier: NCT03852498|
Recruitment Status : Recruiting
First Posted : February 25, 2019
Last Update Posted : January 19, 2021
Study ALD-104 is an international, non-randomized, open-label, multi-site study in male participants (<or=17 years of age at enrollment) with cerebral adrenoleukodystrophy (CALD). Approximately 35 participants will be infused with Lenti-D Drug Product after myeloablative conditioning with busulfan and fludarabine.
This trial will evaluate the efficacy and safety of autologous cluster of differentiation 34 (CD34+) hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector, for the treatment of CALD. A subject's blood stem cells will be collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells will be transplanted back into the subject following myeloablative conditioning.
|Condition or disease||Intervention/treatment||Phase|
|Cerebral Adrenoleukodystrophy (CALD)||Genetic: Lenti-D||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 3 Study of Lenti-D Drug Product After Myeloablative Conditioning Using Busulfan and Fludarabine in Subjects ≤17 Years of Age With Cerebral Adrenoleukodystrophy (CALD)|
|Actual Study Start Date :||January 24, 2019|
|Estimated Primary Completion Date :||February 2024|
|Estimated Study Completion Date :||February 2024|
|Experimental: Lenti-D Drug Product||
Lenti-D Drug Product (autologous CD34+ cell-enriched population that contains cells transduced with Lenti-D lentiviral vector that encodes an ABCD1 complementary deoxyribonucleic acid complementary DNA (cDNA) for human adrenoleukodystrophy protein, suspended in a cryopreservation solution) is administered intravenously. Lenti-D Drug Product is administered by IV infusion following myeloablative conditioning with busulfan and fludarabine.
- Percentage of Participants who are Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 [ Time Frame: Month 24 post-transplant ]The MFDs are loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, complete loss of voluntary movement.
- Percentage of Participants with Neutrophil Engraftment After Drug Product Infusion [ Time Frame: 42 days post-drug product infusion ]
- Percentage of Participants Without Gadolinium Enhancement (GdE) at Month 24 [ Time Frame: Month 24 post-transplant ]Percentage of participants without Gadolinium Enhancement (that is [i.e.,] negative for Gadolinium Enhancement [GdE-]) on Magnetic Resonance Imaging (MRI).
- Value and Change in Total Neurologic Function Score (NFS) From Baseline to Protocol Scheduled Visits [ Time Frame: From Baseline through study completion (up to Month 24 [+or- 1 month] post-transplant) ]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 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.
- Major Functional Disability (MFD)-Free Survival Over Time [ Time Frame: up to Month 24 (+or- 1 month) post-transplant ]MFD-free survival over time is defined as time from drug product infusion to either a rescue cell administration or second transplant, MFD, or death due to any cause, whichever occurs first.
- Overall Survival [ Time Frame: up to Month 24 (+or- 1 month) post-transplant ]
- Detectable vector copy number (VCN) in peripheral blood cells by Month 6 [ Time Frame: Month 6 post-transplant ]
- Percentage of Participants who experience either acute (Greater Than or Equal to [>or=] Grade II) or chronic Grafts versus Host Disease (GVHD) at Month 24 [ Time Frame: Month 24 post-transplant ]
- Time to Neutrophil Engraftment Post-drug Product Infusion [ Time Frame: 42 days post-drug product infusion ]
- Percentage of Participants with Platelet Engraftment by Month 24 [ Time Frame: Month 24 post-drug product infusion ]
- Time to Platelet Engraftment Post-drug Product Infusion [ Time Frame: up to Month 24 post-drug product infusion ]
- Percentage of Participants with Loss of Neutrophil Engraftment Post-drug Product Infusion by Month 24 [ Time Frame: Month 24 post-drug product infusion ]
- Percentage of Participants who Undergo a Subsequent Hematopoietic Stem Cell (HSC) Infusion by Month 24 [ Time Frame: Month 24 post-transplant ]
- Percentage of Participants who Experience Transplant-Related Mortality Through 100 and 365 days post-drug product infusion [ Time Frame: Through 100 and 365 days post-drug product infusion ]
- Percentage of Participants with Adverse Events (AEs) in Selected Categories [ Time Frame: Month 24 post-transplant ]Percentage of participants with clinical greater than or equal to (> or =) Grade 3 AEs, investigational medicinal product (IMP)-related AEs, all serious adverse events (SAEs), AEs > or = Grade 3 infections by Month 24.
- Percentage of Participants with Potentially Clinically Significant Changes in Laboratory Parameters by Month 24 [ Time Frame: Month 24 post-transplant ]Laboratory parameters will include hematology, clinical chemistry, and liver function tests.
- Percentage of Participants who Experience Greater Than or Equal to (>or=) Grade II Acute GVHD by Month 24 [ Time Frame: Month 24 post-transplant ]
- Percentage of Participants who Experience Chronic GVHD by Month 24 [ Time Frame: Month 24 post-transplant ]
- Number of Emergency Room Visits (Post-Neutrophil Engraftment) by Month 24 [ Time Frame: Month 24 post-transplant ]
- Number of in-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24 [ Time Frame: Month 24 post-transplant ]
- Duration of in-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24 [ Time Frame: Month 24 post-transplant ]
- Number of Intensive Care Units (ICU) Stays (post-neutrophil engraftment) by Month 24 [ Time Frame: Month 24 post-transplant ]
- Duration of Intensive Care Units (ICU) Stays (post-neutrophil engraftment) by Month 24 [ Time Frame: Month 24 post-transplant ]
- Number of Participants in which Vector-Derived Replication Competent Lentivirus (RCL) is Detected by Month 24 [ Time Frame: Month 24 post-transplant ]
- Number of Participants with Insertional Oncogenesis by Month 24 [ Time Frame: Month 24 post-transplant ]Insertional oncogenesis including Myelodysplasia, Leukemia, Lymphoma by Month 24.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03852498
|Contact: bluebird bio||(339) email@example.com|
|United States, California|
|Lucile Packard Children's Hospital||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Elisabeth Merkel 650-497-6746 firstname.lastname@example.org|
|Principal Investigator: Ami Shah, MD|
|United States, Massachusetts|
|Boston Children's Hospital/Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Colleen Dansereau 617-919-7008 Colleen.Dansereau@childrens.harvard.edu|
|Principal Investigator: Christine Duncan, MD|
|Principal Investigator: Florian Eichler, MD|
|United States, Minnesota|
|University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Ashish Gupta, MD email@example.com|
|Contact: Troy Lund, MD firstname.lastname@example.org|
|Principal Investigator: Paul Orchard, MD|
|Hôpital Robert Debré||Recruiting|
|Paris, France, 75019|
|Contact: Jean-Hugues Dalle, MD, PhD +33 (0)1.40.03.53.88 email@example.com|
|Principal Investigator: Jean-Hugues Dalle, MD, PhD|
|Universitätsklinikum Leipzig AöR||Recruiting|
|Leipzig, Germany, 04103|
|Contact: Sven Starke, MD +49 (0) 341 97 26917 firstname.lastname@example.org|
|Principal Investigator: Jörn Kühl, MD|
|Ospedale Pediatrico Bambino Gesù||Recruiting|
|Rome, Italy, 00165|
|Contact: Franco Locatelli, MD +39 06 68592129 email@example.com|
|Principal Investigator: Franco Locatelli, MD|
|Prinses Maxima Center||Recruiting|
|Utrecht, Netherlands, 3508AB|
|Contact: Caroline Lindemans, MD, PhD +31-6-500029501 firstname.lastname@example.org|
|Principal Investigator: Caroline Lindemans, MD, PhD|
|UCL-ICH/Great Ormond Street Hospital||Recruiting|
|London, United Kingdom, WC1N3JH|
|Contact: Lynsey Hart email@example.com|
|Contact: Camilla Duran-Person Camilla.Duran_Persson@gosh.nhs.uk|
|Principal Investigator: Adrian Thrasher, MD, PhD|
|Principal Investigator: Robert Chiesa, MD|
|Study Director:||Andrew Dietz, MD||bluebird bio, Inc.|