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    Summary
    EudraCT Number:2015-004122-33
    Sponsor's Protocol Code Number:HGB-207
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-05-05
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2015-004122-33
    A.3Full title of the trial
    A Phase 3 Single Arm Study Evaluating the Efficacy and Safety of Gene Therapy in Subjects with Transfusion-dependent β-Thalassemia, who do not have β0/β0 Genotype, by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with a Lentiviral βA-T87Q-Globin Vector in Subjects ≥12 and ≤50 Years of Age
    Studio di fase 3, a braccio singolo, volto a valutare l’efficacia e la sicurezza della terapia genica in soggetti affetti da β-Talassemia trasfusione dipendente, genotipicamente non β0/β0, applicata con trapianto di cellule staminali autologhe CD34+ trasdotte ex vivo mediante un vettore lentivirale del gene globinico βA-T87Q in soggetti di età compresa tra ≥12 e ≤50 anni
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    NA
    A.4.1Sponsor's protocol code numberHGB-207
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/297/2016
    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 (with its wholly owned subsidiary bluebird bio France)
    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 Trials Operations
    B.5.3 Address:
    B.5.3.1Street Address150 Second Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post code02141
    B.5.3.4CountryUnited States
    B.5.4Telephone number0013394999300
    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/3/12/1091
    D.3 Description of the IMP
    D.3.1Product nameLentiGlobin BB305 Drug Product (autologous CD34+ cells transduced with LentiGlobin BB305)
    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.3.9.3Other descriptive nameAutologous CD34+ cell-enriched population that contains cells transduced with LentiGlobin BB305 lentiviral vector encoding human beta-A-T87Q-globin
    D.3.9.4EV Substance CodeSUB127985
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number1000000 to 20000000
    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 numberEMA/CAT/988303/2011
    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.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
    This study will enroll subjects with transfusion dependent beta-thalassemia, who do not have beta0/beta0 genotype, defined by a history of at least 100 mL/kg/year of packed red blood cells (pRBCs) or ≥ 8 transfusions of pRBCs per year in the 2 years preceding enrollment.
    E.1.1.1Medical condition in easily understood language
    beta-thalassemia
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10054660
    E.1.2Term Thalassemia beta
    E.1.2System Organ Class 100000004850
    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 of treatment with LentiGlobin BB305 Drug Product in subjects ≥12 and ≤50 of age with transfusion-dependent beta-thalassemia, who do not have beta0/beta0 genotype.
    E.2.2Secondary objectives of the trial
    To evaluate the safety of treatment with LentiGlobin BB305 Drug Product in subjects ≥12 and ≤50 of age with transfusion-dependent beta-thalassemia, who do not have beta0/beta0 genotype.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subjects between 12 and 50 years of age, inclusive
    2. Diagnosis of transfusion-dependent thalassemia (including severe HbE/beta-thalassemia), also known as beta-thalassemia major, with a history of at least 100 mL/kg/year of pRBCs or ≥ 8 transfusions of pRBCs per year for the prior 2 years
    3. Clinically stable and eligible to undergo HSCT
    4. Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records on RBC transfusions, in-patient hospitalization, and iron chelation history
    E.4Principal exclusion criteria
    1. Presence of a mutation characterized as beta0 on both HBB alleles. For the purpose of this study, the HBB mutation IVS I-110 (G -> A) will be considered equivalent to beta0 and be excluded
    2. Positive for presence of HIV-1 or HIV-2, HBV, or HCV
    3. Clinically significant and active bacterial, viral, fungal, or parasitic infection
    4. A WBC count < 3 × 10^9/L, and/or platelet count < 100 × 10^9/L not related to hypersplenism
    5. Uncorrected bleeding disorder
    6. Any prior or current malignancy or myeloproliferative or significant immunodeficiency disorder
    7. Immediate family member with a known Familial Cancer Syndrome
    8. Prior HSCT
    9. Advanced liver disease
    10. Baseline estimated glomerular filtration rate < 70 mL/min/1.73 m^2
    11. Uncontrolled seizure disorder
    12. Diffusion capacity of carbon monoxide (DLco) < 50% of predicted
    13. A cardiac T2* < 10 ms by MRI
    14. Any other evidence of severe iron overload that warrants exclusion
    15. Participation in another clinical study with an investigational drug within 30 days of Screening
    16. Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician or investigator
    17. Prior receipt of gene therapy
    18. Diagnosis of significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study
    19. Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects
    20. An assessment by the investigator that the subject would not comply with the study procedures outlined in the protocol
    21. A known and available HLA-matched family donor
    E.5 End points
    E.5.1Primary end point(s)
    EFFICACY ENDPOINT
    - The proportion of subjects who meet the definition of “transfusion independence” (TI).
    E.5.1.1Timepoint(s) of evaluation of this end point
    24 months
    E.5.2Secondary end point(s)
    EFFICACY ENDPOINTS
    - Characterization of subjects achieving transfusion independence
    - Transfusion-free survival
    - Characterization of transfusion reduction (TR) among subjects not achieving TI
    - Trend in hemoglobin pre- and post-treatment
    - Characterization of use of iron chelation among all subjects
    - Evaluation of the change in iron burden over time

    EXPLORATORY EFFICACY ENDPOINTS
    - Evaluation of health-related quality of life (HRQoL) over time
    - Assessment of growth and puberty parameters (age appropriate), bone density, diabetes, endocrine evaluations, and neurocognitive development (pediatric subjects < 18 years of age)
    - Assessment of improvement in ineffective erythropoiesis
    - Correlations of pre-treatment variables with response
    - Measures of health resource utilization

    PHARMACODYNAMIC ENDPOINTS
    - βA-T87Q-globin expression
    - VCN in cell populations from peripheral blood

    EXPLORATORY PHARMACODYNAMIC ENDPOINT
    - Relationship between measures of myeloablation and pharmacodynamic and clinical outcomes

    SAFETY ENDPOINTS
    - Success and kinetics of HSC engraftment
    - Incidence of transplant-related mortality through 100 days post-drug product infusion
    - Overall survival
    - Detection of vector-derived replication competent lentivirus in any subject
    - Characterization of events of insertional mutagenesis leading to clonal dominance or leukemia
    - Monitoring of laboratory parameters and frequency and severity of clinical adverse events
    E.5.2.1Timepoint(s) of evaluation of this end point
    24 months
    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 Yes
    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 Yes
    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 EEA6
    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
    France
    Germany
    Greece
    Italy
    Thailand
    United Kingdom
    United States
    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
    The study will end when the last subject completes the Month 24 visit or discontinues from the study.
    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 months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months6
    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: 5
    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) No
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 5
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 10
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    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 Yes
    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 No
    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 7
    F.4.2.2In the whole clinical trial 15
    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)
    After completion of HGB-207, subjects will be followed for long-term safety and efficacy under a separate protocol for 13 years. Thus, subjects will be followed for a total of 15 years post-transplant.
    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 Decision2016-09-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-11-10
    P. End of Trial
    P.End of Trial StatusCompleted
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