Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44238   clinical trials with a EudraCT protocol, of which   7338   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2018-001145-14
    Sponsor's Protocol Code Number:ALD-104
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-11-27
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - PEI
    A.2EudraCT number2018-001145-14
    A.3Full title of the trial
    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)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical study to assess the efficacy and safety of gene therapy for the treatment of cerebral adrenoleukodystrophy (CALD)
    A.4.1Sponsor's protocol code numberALD-104
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03852498
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of Sponsorbluebird bio, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportbluebird bio, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationbluebird bio, Inc.
    B.5.2Functional name of contact pointClinical Trial Information
    B.5.3 Address:
    B.5.3.1Street Address455 Grand Union Boulevard
    B.5.3.2Town/ citySomerville, MA
    B.5.3.3Post code02145
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 339 4999300
    B.5.6E-mailclinicaltrials@bluebirdbio.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/12/1003
    D.3 Description of the IMP
    D.3.1Product nameLenti-D Drug Product
    D.3.4Pharmaceutical form Dispersion for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNelivaldogene autotemcel
    D.3.9.3Other descriptive nameAutologous haematopoietic stem cells transduced with lentiviral vector Lenti-D encoding the human ABCD1 cDNA
    D.3.9.4EV Substance CodeSUB127987
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number5000000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Yes
    D.3.11.3.5.1CAT classification and reference numberGene Therapy Medicinal Product Reference Number: EMA/CAT/988313/2011
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms Yes
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNplerixafor
    D.3.9.1CAS number 110078-46-1
    D.3.9.3Other descriptive namePLERIXAFOR
    D.3.9.4EV Substance CodeSUB28849
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Cerebral Adrenoleukodystrophy (CALD)
    E.1.1.1Medical condition in easily understood language
    Cerebral Adrenoleukodystrophy (CALD)
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10051260
    E.1.2Term Adrenoleukodystrophy
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy and safety of Lenti-D Drug Product (also known as elivaldogene autotemcel or Skysona, hereafter referred to as eli-cel) after myeloablative conditioning with busulfan and fludarabine in subjects with CALD
    E.2.2Secondary objectives of the trial
    N/A
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Informed consent is obtained from a competent custodial parent or guardian with legal capacity to execute a local Institutional Review Board (IRB)/Independent Ethics Committee (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 CALD as defined by:
    a. Elevated very long chain fatty acids (VLCFA) values, and
    b. Active central nervous system (CNS) disease established by central radiographic review of brain magnetic resonance imaging (MRI) demonstrating
    i. Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and
    ii. Gadolinium enhancement (GdE) on MRI of demyelinating lesions.
    4. Neurologic Function Score (NFS) ≤1.
    E.4Principal 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:
    a. Peripheral blood absolute neutrophil count (ANC) count <1500 cells/mm3, and either
    b. Platelet count <100,000 cells/mm3, or
    c. Hemoglobin <10 g/dL.
    6. Hepatic compromise as evidenced by:
    a. Aspartate transaminase (AST) value >2.5 × upper limit of normal (ULN)
    b. Alanine transaminase (ALT) value >2.5 × ULN
    c. 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, as determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation (see https://www.kidney.org/professionals/KDOQI/gfr_calculatorPed)
    8. Cardiac compromise as evidenced by left ventricular ejection fraction <40%
    9. Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome, and familial adenomatous polyposis).
    10. Clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or prion associated infection.
    11. Positive for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2); hepatitis B virus (HBV); hepatitis C virus (HCV); human T lymphotrophic virus 1 (HTLV-1). (Note that subjects who have been vaccinated against HBV [positive for HBV surface antibodies] who are negative for other markers of prior HBV infection [e.g., negative for hepatitis B core antibody {HBVc Ab}] are eligible. Subjects with past exposure to HBV [HBc antibodies {Ab} positive and/or hepatitis B e-antigen antibody {HBeAb}-positive] are also eligible for the study provided they have a negative test for HBV deoxyribonucleic acid [DNA]. Also note that subjects who are positive for anti-hepatitis C Ab are eligible as long as they have a negative hepatitis C viral load).
    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. Male subjects and their female partners are required to use two different effective methods of contraception from Screening through at least 6 months after eli-cel infusion. If subjects are truly sexually abstinent (where true sexual abstinence is defined as being in line with the preferred and usual lifestyle of the subject), no second method is required.
    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.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is:
    Proportion of subjects who are alive and have none of the 6 MFDs at Month 24 (i.e. Month 24 MFD-free survival).
    MFDs are:
    o loss of communication
    o cortical blindness
    o tube feeding
    o total incontinence
    o wheelchair dependence
    o complete loss of voluntary movement

    The primary safety endpoint is:
    The proportion of subjects with neutrophil engraftment after drug product infusion.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Month 24
    E.5.2Secondary end point(s)
    Secondary efficacy endpoints are the following:
    • Proportion of subjects without GdE on MRI (i.e., GdE-) at Month 24
    • Value and change in total NFS from Baseline to protocol scheduled visits
    • MFD-free survival over time
    • Overall survival
    • Detectable vector copy number (VCN) in peripheral blood cells by Month 6

    The secondary safety endpoints are the following:
    • The proportion of subjects who experience either acute (≥Grade II) or chronic graft versus host disease (GVHD) by Month 24
    • Time to neutrophil engraftment post-drug product infusion
    • The proportion of subjects with platelet engraftment by Month 24
    • Time to platelet engraftment post-drug product infusion
    • The proportion of subjects with loss of neutrophil engraftment pos-tdrug product infusion by Month 24
    • The proportion of subjects who undergo a subsequent HSC infusion by Month 24
    • The proportion of subjects who experience transplant-related mortality through 100 and 365 days post-drug product infusion
    • Proportion of subjects with clinical ≥ Grade 3 adverse events (AEs), all drug product-related AEs, all serious adverse events (SAEs), ≥ Grade 3 infections, and clinically significant changes in laboratory parameters by Month 24
    • The proportion of subjects who experience ≥Grade II acute GVHD by Month 24
    • The proportion of subjects who experience chronic GVHD by Month 24
    • Number of emergency room visits (post-neutrophil engraftment) by Month 24
    • Number and duration of in-patient hospitalizations (post-neutrophil engraftment) by Month 24
    • Number and duration of intensive care unit (ICU) stays (post-neutrophil engraftment) by Month 24
    • The number of subjects in which vector-derived replication competent lentivirus (RCL) is detected by Month 24
    • The number of subjects with insertional oncogenesis (myelodysplasia, leukemia, lymphoma, etc.) by Month 24
    E.5.2.1Timepoint(s) of evaluation of this end point
    Month 24
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA5
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United States
    France
    Germany
    Italy
    Netherlands
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 35
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 25
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 10
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female No
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Paediatric patients
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 15
    F.4.2.2In the whole clinical trial 35
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Subjects will be asked to enroll into a long-term follow-up study (LTF-304, EudraCT number: 2015-002805-13).
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-06-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-01-23
    P. End of Trial
    P.End of Trial StatusCompleted
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA