COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Clinical Study to Assess the Efficacy and Safety of Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy (CALD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03852498
Recruitment Status : Recruiting
First Posted : February 25, 2019
Last Update Posted : October 6, 2020
Information provided by (Responsible Party):
bluebird bio

Brief Summary:

Study ALD-104 is an international, non-randomized, open-label, multi-site study in male subjects (≤17 years of age at enrollment) with cerebral adrenoleukodystrophy (CALD). Approximately 35 subjects 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 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) Drug: Lenti-D; elivaldogene autotemcel Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Arm Intervention/treatment
Experimental: Lenti-D Drug Product Drug: Lenti-D; elivaldogene autotemcel
Lenti-D Drug Product (autologous CD34+ cell-enriched population that contains cells transduced with Lenti-D lentiviral vector that encodes an ABCD1 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.

Primary Outcome Measures :
  1. Proportion of subjects who are alive and have none of the 6 major functional disabilities (MFDs) at Month 24 (i.e. Month 24 MFD-free survival). [ Time Frame: At 24 months (±1 months) post-transplant ]

    MFDs are:

    • loss of communication
    • cortical blindness
    • tube feeding
    • total incontinence
    • wheelchair dependence
    • complete loss of voluntary movement

  2. The proportion of subjects with neutrophil engraftment after drug product infusion. [ Time Frame: At 42 days post-drug product infusion ]

Secondary Outcome Measures :
  1. Proportion of subjects without gadolinium enhancement on MRI (i.e., GdE-) at Month 24. [ Time Frame: At 24 months (±1 months) post-transplant ]
  2. Value and change in total Neurologic Function Score (NFS) from Baseline to protocol scheduled visits. [ Time Frame: From Baseline through study completion, an average of 2 years ]
  3. MFD-free survival over time. [ Time Frame: From drug product infusion through study completion, an average of 2 years ]
  4. Overall survival. [ Time Frame: From drug product infusion through study completion, an average of 2 years ]
  5. Detectable vector copy number (VCN) in peripheral blood cells by Month 6. [ Time Frame: Up to 6 months (+/- 14 days) post-transplant ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Informed consent is obtained from a competent custodial parent or guardian with legal capacity to execute a local IRB/IEC approved consent. Informed assent will be sought from capable subjects, in accordance with the directive of the IRB/IEC and with local requirements.
  2. Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, subject assent.
  3. Active cerebral ALD as defined by:

    1. Elevated very long chain fatty acids (VLCFA) values, and
    2. Active central nervous system (CNS) disease established by central radiographic review of brain MRI demonstrating

    i. Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and ii. Gadolinium enhancement on MRI of demyelinating lesions.

  4. Neurologic Function Score (NFS) ≤1.

Exclusion Criteria:

  1. Prior receipt of an allogeneic transplant or gene therapy.
  2. Use of statins, Lorenzo's Oil, or dietary regimens used to lower VLCFA levels. Note: subjects must discontinue use of these medications at time of consent.
  3. Receipt of an investigational study drug or procedure within 3 months before Screening that might confound study outcomes. Use of investigational study drugs is prohibited throughout the course of the study.
  4. Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).
  5. Hematological compromise as evidenced by:

    1. Peripheral blood ANC count <1500 cells/mm3, and either
    2. Platelet count <100,000 cells/mm3, or
    3. Hemoglobin <10 g/dL.
  6. Hepatic compromise as evidenced by:

    1. Aspartate transaminase (AST) value >2.5 × ULN
    2. Alanine transaminase (ALT) value >2.5 × ULN
    3. Total bilirubin value >3.0 mg/dL, except if there is a diagnosis of Gilbert's Syndrome and the subject is otherwise stable
  7. Baseline estimated glomerular filtration rate <70 mL/min/1.73 m2
  8. Cardiac compromise as evidenced by left ventricular ejection fraction <40%
  9. Immediate family member with a known or suspected Familial Cancer Syndrome
  10. Clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or prion associated infection.
  11. Positive for HIV, hepatitis B or C virus, or human T lymphotrophic virus 1 (HTLV-1)
  12. Any clinically significant cardiovascular, hematological, or pulmonary disease, or other disease or condition that would be contraindicated for any of the other study procedures.
  13. Absence of adequate contraception for fertile subjects.
  14. Any contraindications to the use of G-CSF or plerixafor during the mobilization of hematopoietic stem cells, and any contraindications to the use of busulfan or fludarabine, including known hypersensitivity to the active substances or to any of the excipients in their formulations.
  15. Known hypersensitivity to protamine sulfate.

Information from the National Library of Medicine

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 identifier (NCT number): NCT03852498

Layout table for location contacts
Contact: bluebird bio (339) 499-9300

Layout table for location information
United States, California
Lucile Packard Children's Hospital Recruiting
Palo Alto, California, United States, 94304
Contact: Elisabeth Merkel    650-497-6746   
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   
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   
Contact: Troy Lund, MD   
Principal Investigator: Paul Orchard, MD         
Hôpital Robert Debré Recruiting
Paris, France, 75019
Contact: Jean-Hugues Dalle, MD, PhD    +33 (0)   
Principal Investigator: Jean-Hugues Dalle, MD, PhD         
Ospedale Pediatrico Bambino Gesù Recruiting
Rome, Italy, 00165
Contact: Franco Locatelli, MD    +39 06 68592129   
Principal Investigator: Franco Locatelli, MD         
Prinses Maxima Center Recruiting
Utrecht, Netherlands, 3508AB
Contact: Caroline Lindemans, MD, PhD    +31-6-500029501   
Principal Investigator: Caroline Lindemans, MD, PhD         
United Kingdom
UCL-ICH/Great Ormond Street Hospital Recruiting
London, United Kingdom, WC1N3JH
Contact: Lynsey Hart   
Contact: Camilla Duran-Person   
Principal Investigator: Adrian Thrasher, MD, PhD         
Principal Investigator: Robert Chiesa, MD         
Sponsors and Collaborators
bluebird bio
Layout table for investigator information
Study Director: Andrew Dietz, MD bluebird bio, Inc.
Layout table for additonal information
Responsible Party: bluebird bio Identifier: NCT03852498    
Other Study ID Numbers: ALD-104
First Posted: February 25, 2019    Key Record Dates
Last Update Posted: October 6, 2020
Last Verified: October 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by bluebird bio:
X-linked adrenoleukodystrophy
Gene therapy
Hematopoietic stem cell
Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hereditary Central Nervous System Demyelinating Diseases
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