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   43865   clinical trials with a EudraCT protocol, of which   7286   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:2019-000331-63
    Sponsor's Protocol Code Number:HGB-210
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2020-07-06
    Trial 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 ConcernedUK - MHRA
    A.2EudraCT number2019-000331-63
    A.3Full title of the trial
    A Phase 3 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with the LentiGlobin BB305 Lentiviral Vector in Subjects with Sickle Cell Disease.
    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 Sickle Cell Disease
    A.4.1Sponsor's protocol code numberHGB-210
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/234/2019
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of Sponsor bluebird 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 Address60 Binney Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02142
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 339 499 9300
    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/3/14/1263
    D.3 Description of the IMP
    D.3.1Product nameLentiGlobin BB305 Drug Product for Sickle Cell Disease (also known as bb1111)
    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+ CELLS TRANSDUCED WITH BB305 VECTOR ENCODING 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 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 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
    Sickle Cell Disease
    E.1.1.1Medical condition in easily understood language
    Sickle Cell Disease
    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 21.0
    E.1.2Level PT
    E.1.2Classification code 10040644
    E.1.2Term Sickle cell disease
    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 of treatment with LentiGlobin BB305 Drug Product in subjects with sickle cell disease (SCD).
    E.2.2Secondary objectives of the trial
    To evaluate the safety of treatment with LentiGlobin BB305 Drug Product in subjects with SCD
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Have a diagnosis of SCD, with either βS/βS, βS/β0 or βS/β+ genotype.
    2. Be ≥2 and ≤50 years of age at time of consent.
    3. Weigh a minimum of 6 kg.
    4. Have a Karnofsky performance status of ≥60 (≥16 years of age) or a Lansky performance status of ≥60 (<16 years of age).
    5. Be treated and followed for at least the past 24 months prior to Informed Consent in medical center(s) that maintained detailed records on sickle cell disease history.
    6. Have severe manifestations of SCD. i.e. in the setting of appropriate supportive care measures (e.g., pain management plan), have experienced at least 4 severe VOEs in the 24 months prior to informed consent as defined below. For the purposes of this study, a severe VOE is defined as an event with no medically determined cause other than a vaso-occlusion, requiring a ≥24 -hour hospital or emergency room (ER) observation unit visit or at least 2 visits to a day unit or ER over 72 hours with both visits requiring intravenous treatment. Exception: priapism does not require hospital admission but does require a medical facility visit; 4 priapism episodes that require a visit to a medical facility (without inpatient admission) are sufficient to meet criterion.
    7. Have either experienced HU failure at any point in the past or must have intolerance to HU (intolerance is defined as the patient being unable to continue to take HU per PI judgment).
    E.4Principal exclusion criteria
    1. Applicable to subjects <18 years of age only: Availability of a willing, matched human leukocyte antigen (HLA)-identical sibling HSC donor.
    2. Severe cerebral vasculopathy, defined by any history of: overt ischemic or hemorrhagic stroke, abnormal transcranial Doppler (>200 cm/sec based on central read) requiring chronic transfusion, occlusion or stenosis in the circle of Willis, or presence of Moyamoya disease.
    3. Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), hepatitis B, hepatitis C, human T-lymphotrophic virus-1 (HTLV-1) or -2 (HTLV-2), active syphilis.
    4. Clinically significant, active bacterial, viral, fungal, or parasitic infection
    5. Advanced liver disease, such as
    a. clear evidence of liver cirrhosis, active hepatitis or significant fibrosis (based on MRI or liver biopsy)
    b. liver iron concentration ≥15 mg/g unless liver biopsy shows no evidence of cirrhosis, active hepatitis or significant fibrosis
    6. Inadequate bone marrow function, as defined by an absolute neutrophil count of <1×10^9/L (<0.5×10^9/L for subjects on hydroxyurea treatment) or a platelet count <100×10^9/L.
    7. Any contraindications to the use of plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.
    8. Patients needing therapeutic anticoagulation treatment during the period of conditioning through platelet engraftment
    9. Unable to receive red blood cell (RBC) transfusion.
    10. Prior receipt of an allogeneic HSC transplant.
    11. Prior receipt of gene therapy.
    12. Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin.
    13. Immediate family member with a known or suspected Familial Cancer Syndrome.
    14. Pregnancy, or breastfeeding in a postpartum female, or absence of adequate contraception for fertile subjects.
    15. Any other condition that would render the subject ineligible for HSCT.
    16. Participation in another clinical study with an investigational drug within 30 days of screening
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of subjects meeting Globin Response criteria
    Subjects must meet the below criteria for a continuous period of at least 6 months after drug product infusion in order to be considered having achieved Globin response:
    a. Weighted average HbAT87Q percentage of total Hb* ≥30% AND
    b. Weighted average total Hb* increase of ≥3 g/dL compared to baseline total Hb* OR weighted average total Hb* ≥10 g/dL
    -total Hb is the non-transfused total Hb; it is HbS + HbF + HbA2 + HbAT87Q
    E.5.1.1Timepoint(s) of evaluation of this end point
    1-24 months post-transplant
    E.5.2Secondary end point(s)
    •Percent of subjects reaching a 75% reduction in annualized severe vaso-occlusive events (sVOE-75) in the 24 months after drug product administration compared to the 24 months prior to Informed Consent.
    •Weighted average non-transfused total Hb
    •Weighted average HbS percentage of non-transfused total Hb
    •Weighted average HbS percentage of non-transfused total Hb ≤70%, ≤60%, ≤50%
    •Weighted average HbAT87Q percentage of non-transfused total Hb
    •Weighted average non-HbS percentage of non-transfused total Hb
    •Average and median of non-transfused total Hb over time
    •Average and median of HbS percentage of non-transfused total Hb over time
    •Average and median of HbAT87Q percentage of non-transfused total Hb over time
    •Average and median of non-HbS percentage of non-transfused total Hb over time
    •Change from baseline in absolute reticulocyte count
    •Change from baseline in percent reticulocytes
    •Change from baseline in percent erythrocytes
    •Change from baseline in total bilirubin
    •Change from baseline in haptoglobin
    •Change from baseline in lactate dehydrogenase
    •Change from baseline in iron
    •Change from baseline in ferritin
    •Change from baseline in transferrin saturation
    •Change from baseline in liver iron content
    •Change from baseline in cardiac iron content (if assessed at baseline)
    •Change from baseline in erythropoietin
    •Change from baseline in serum transferrin receptor
    •Change in the annualized number of severe VOEs in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent.
    •Change in the annualized number of VOEs in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent
    •Proportion of subjects achieving severe VOE-complete resolution (sVOE-CR)
    Defined as complete resolution of severe VOEs between 6 months and 24 months after drug product administration
    •Proportion of subjects achieving reduction in the annualized number of severe VOEs of at least 90% in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent.
    •Change from baseline in annualized frequency transfusions
    •Change from baseline in volume of packed red blood cell (pRBC) transfusions
    •Change from baseline in cerebral vasculature and prior brain parenchymal injury
    As measured by cerebral MRA/MRI in all subjects, and transcranial doppler (TCD) for subjects ≤16 years old at Informed Consent
    •Change from baseline in bone mineral density (BMD) evaluation using dual x-ray (DXA) absorptiometry
    •Proportion of subjects with the development of osteonecrosis in new joints needing any specific therapeutic procedure
    •Proportion of subjects with new or worsening retinopathy complications needing any specific therapeutic procedure
    •Proportion of subjects with new or worsening severe leg ulcers needing wound care specialized follow-up
    •Change from baseline in proteinuria
    •Change from baseline in microalbuminuria
    •Change from baseline in estimated glomerular filtration rate (eGFR)
    •Change from baseline in cardiac-pulmonary function via echocardiogram
    •Change from baseline in cardiac-pulmonary function via pulmonary function test
    •Change from baseline in cardiac-pulmonary function via brain natriuretic peptide
    •Change from baseline in meters walked during 6-minute walk test
    •Change from baseline in annualized number of hospital admissions
    •Change from baseline in annualized number of total days hospitalized
    •Change from baseline in patient-reported quality of life, as measured by Patient Reported Outcomes Measurement Information System-57 (PROMIS-57)

    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 No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    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
    Italy
    Netherlands
    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
    LPLV
    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 months3
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months3
    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: 20
    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: 12
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 8
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 15
    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 state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 17
    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
    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 Decision2020-09-07
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial Status
    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-Mon Apr 29 17:11:58 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA