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

• ClinicalTrials.gov Identifier: NCT02698579
• Recruitment Status: Enrolling by invitation
• First Posted: March 3, 2016
• Last Update Posted: March 30, 2023
• Sponsor: bluebird bio
• Information provided by (Responsible Party): bluebird bio

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Cerebral Adrenoleukodystrophy (CALD); Adrenoleukodystrophy (ALD); X-Linked Adrenoleukodystrophy (X-ALD)	Genetic: Lenti-D Drug Product

Study Design

• Study Type: Observational
• Estimated Enrollment: 67 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Long-term Follow-up of Subjects With Cerebral Adrenoleukodystrophy Who Were Treated With Lenti-D Drug Product
• Actual Study Start Date: January 22, 2016
• Estimated Primary Completion Date: May 2037
• Estimated Study Completion Date: May 2037

Groups and Cohorts

Group/Cohort	Intervention/treatment
Lenti-D Drug Product; 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; Vector copy number (VCN) measurement, safety evaluations, disease-specific assessments, and assessments to monitor for long-term complications of autologous transplant.; Other Names: elivaldogene autotemcel; eli-cel

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Number of participants who undergo subsequent stem cell transplantation [ Time Frame: 15 years post-drug-product infusion ]
2. Change from baseline in neurological function score (NFS) [ Time Frame: 15 years post-drug-product infusion ]
   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.
3. Number of participants without gadolinium enhancement (GdE) status on magnetic resonance imaging (MRI) [ Time Frame: 15 years post-drug-product infusion ]
   GdE status means participants who will report GdE negative (-) or positive (+).

Eligibility Criteria

• Ages Eligible for Study: up to 17 Years (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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.

Criteria

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

Contacts and Locations

Locations

United States, California

Mattel Children's Hospital-UCLA

Los Angeles, California, United States, 90095

Lucile Packard Children's Hospital - Stanford

Palo Alto, California, United States, 94304

United States, Massachusetts

Boston Children's Hospital/Massachusetts General Hospital

Boston, Massachusetts, United States, 02115

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

Argentina

Instituto Neurogenia

Caba, Argentina

Australia

Women's and Children's Hospital

North Adelaide, Australia

Brazil

Hospital das Clínicas da Universidade de São Paulo

São Paulo, Brazil, 05403-000

France

Hôpital Bicêtre

Le Kremlin-Bicêtre, Cedex, France, 94275

Germany

Universitätsklinikum Leipzig AöR

Leipzig, Germany, 04103

Netherlands

Prinses Maxima Center

Utrecht, Netherlands, 3584

United Kingdom

Great Ormond Street Hospital

London, United Kingdom

Sponsors and Collaborators

bluebird bio

Investigators

• Study Director: Himal Lal Thakar, MD; bluebird bio, Inc.

More Information

Additional Information:

Related Info 

• Responsible Party: bluebird bio
• ClinicalTrials.gov Identifier: NCT02698579
• Other Study ID Numbers: LTF-304; 2015-002805-13 ( EudraCT Number )
• First Posted: March 3, 2016
• Last Update Posted: March 30, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Bluebird bio is committed to transparency and 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by bluebird bio:

Adrenoleukodystrophy; X-linked Adrenoleukodystrophy; Hematopoietic Stem Cells

Additional relevant MeSH terms:

Adrenoleukodystrophy; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases