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Trial record 1 of 1 for:    NCT03852498
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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 : July 31, 2020
Information provided by (Responsible Party):
bluebird bio

Tracking Information
First Submitted Date  ICMJE February 13, 2019
First Posted Date  ICMJE February 25, 2019
Last Update Posted Date July 31, 2020
Actual Study Start Date  ICMJE January 24, 2019
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2019)
  • 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
  • The proportion of subjects with neutrophil engraftment after drug product infusion. [ Time Frame: At 42 days post-drug product infusion ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2019)
  • Proportion of subjects without gadolinium enhancement on MRI (i.e., GdE-) at Month 24. [ Time Frame: At 24 months (±1 months) post-transplant ]
  • 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 ]
  • MFD-free survival over time. [ Time Frame: From drug product infusion through study completion, an average of 2 years ]
  • Overall survival. [ Time Frame: From drug product infusion through study completion, an average of 2 years ]
  • Detectable vector copy number (VCN) in peripheral blood cells by Month 6. [ Time Frame: Up to 6 months (+/- 14 days) post-transplant ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Clinical Study to Assess the Efficacy and Safety of Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy (CALD)
Official Title  ICMJE 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)
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cerebral Adrenoleukodystrophy (CALD)
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: Lenti-D Drug Product
Intervention: Drug: Lenti-D; elivaldogene autotemcel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 14, 2020)
Original Estimated Enrollment  ICMJE
 (submitted: February 21, 2019)
Estimated Study Completion Date  ICMJE February 2024
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE up to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: bluebird bio (339) 499-9300
Listed Location Countries  ICMJE France,   Italy,   United Kingdom,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03852498
Other Study ID Numbers  ICMJE ALD-104
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party bluebird bio
Study Sponsor  ICMJE bluebird bio
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Andrew Dietz, MD bluebird bio, Inc.
PRS Account bluebird bio
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP