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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   33614   clinical trials with a EudraCT protocol, of which   5440   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).
     
    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:2014-003880-38
    Sponsor's Protocol Code Number:270-201
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-06-09
    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 number2014-003880-38
    A.3Full title of the trial
    A Phase 1/2, Dose-Escalation Safety, Tolerability and Efficacy Study of BMN 270, an Adenovirus-Associated Virus Vector–Mediated Gene Transfer of Human Factor VIII in Patients with Severe Haemophilia A
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 1/2 study to evaluate the safety and efficacy of BMN 270 gene therapy in patients with severe Haemophilia A
    A.4.1Sponsor's protocol code number270-201
    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 SponsorBioMarin Pharmaceutical 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 supportBioMarin Pharmaceutical Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBioMarin Pharmaceutical Inc.
    B.5.2Functional name of contact pointClinical Trials Information
    B.5.3 Address:
    B.5.3.1Street Address105 Digital Drive
    B.5.3.2Town/ cityNovato
    B.5.3.3Post code94949
    B.5.3.4CountryUnited States
    B.5.6E-mailmedinfo@bmrn.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/3/16/1622
    D.3 Description of the IMP
    D.3.1Product nameN/A
    D.3.2Product code BMN 270
    D.3.4Pharmaceutical form Solution 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 INNvoloctocogene roxaparvovec
    D.3.9.1CAS number 1819334-78-5
    D.3.9.2Current sponsor codeBMN 270
    D.3.9.3Other descriptive nameAAV-HFVIII-SQ
    D.3.9.4EV Substance CodeSUB174200
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2E13
    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 Yes
    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
    Haemophilia A
    E.1.1.1Medical condition in easily understood language
    Bleeding Disorder
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To assess the safety of a single intravenous administration of a recombinant AAV5 encoding human coagulation FVIII (AAV5-hFVIII-SQ) vector.
    - To determine the dose of AAV5-hFVIII-SQ required to achieve FVIII at or above 5% of normal activity (≥5 IU/dL) at 16 weeks after infusion. The kinetics, duration and magnitude of AAV-mediated FVIII activity in individuals with haemophilia A will be determined and correlated to an appropriate BMN 270 dose.
    E.2.2Secondary objectives of the trial
    - To describe the immune response to the FVIII transgene and AAV capsid proteins following systemic administration of AAV5-hFVIII-SQ
    - To assess the impact of BMN 270 on the frequency of FVIII replacement therapy during the study
    - To assess the impact of BMN 270 on the number of bleeding episodes requiring treatment during the study
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Males that are 18 years or older with established severe haemophilia A as evidenced by their medical history. Patients will be considered as severe if their base FVIII level is 1 IU/dL or less
    2. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs)
    3. Greater or equal to 12 bleeding episodes only if receiving on-demand therapy over the previous 12 months. Does not apply to patients on prophylaxis
    4. Able to sign informed consent and comply with requirements of the trial
    5. No history of inhibitor, and results from a modified Nijmegen Bethesda assay of less than 0.6 Bethesda Units (BU) on 2 consecutive occasions at least one week apart within the past 12 months
    6. Sexually active patients must be willing to use an acceptable method of contraception such as double barrier, including hormonal contraception for at least 6 months post-treatment. After 6 months, subjects may stop contraception use only if they have had 3 consecutive negative semen samples.
    E.4Principal exclusion criteria
    1. Detectable pre-existing immunity to the AAV5 capsid as measured by AAV5 transduction inhibition or AAV5 total antibodies
    2. Any evidence of active infection or any immunosuppressive disorder.
    3. HIV positive
    4. Significant liver dysfunction as defined by abnormal elevation of: ALT (alanine transaminase) to 3 times the upper limit of normal; Bilirubin above 3 times the upper limit of normal; Alkaline phosphatase above 3 times the upper limit of normal; or INR (international normalized ratio) ≥ 1.4.
    5. Potential participants who have had a liver biopsy in the past 3 years are excluded if they had significant fibrosis of 3 or 4 as rated on a scale of 0-4
    6. Evidence of any bleeding disorder not related to Haemophilia A
    7. Platelet count of < 100 x 10^9/L
    8. Creatinine ≥ 1.5 mg/dL
    9. Liver cirrhosis of any etiology as assessed by liver ultrasound
    10. Hepatitis B if surface antigen is positive
    11. Hepatitis C if RNA is positive
    12. Treatment with any IP within 30 days prior to the end of the screening period
    13. Any disease or condition at the physician’s discretion that would prevent the patient from fully complying with the requirements of the study including possible corticosteroid treatment outlined in the protocol. The physician may exclude patients unwilling or unable to agree on not using alcohol for the 16-week period following the viral infusion.
    14. Prior treatment with any vector or gene transfer agent
    15. Major surgery planned in the 16-week period following the viral infusion
    16. Use of systemic immunosuppressive agents or live vaccines within 30 days before the viral infusion
    E.5 End points
    E.5.1Primary end point(s)
    - To assess the safety of a single intravenous administration of a recombinant AAV5 encoding human coagulation FVIII (AAV5-hFVIII-SQ) vector.
    - To determine the dose of AAV5-hFVIII-SQ required to achieve FVIII at or above 5% of normal activity (≥5 IU/dL) at 16 weeks after infusion. The kinetics, duration and magnitude of AAV-mediated FVIII activity in individuals with haemophilia A will be determined and correlated to an appropriate BMN 270 dose.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Safety will be closely monitored during dosing and for 24 hours after dosing. Safety follow-up evaluations will be conducted at least once a week after the infusion for 36 weeks, once every 2 weeks until the end of the first year and then once every three months until the end of the study (in year 5). Dose determination will be evaluated using FVIII activity assays and will be assessed weekly during the first 36 weeks after the infusion, once every 2 weeks until the end of the first year and then once every three months until the end of the study (in year 5).
    E.5.2Secondary end point(s)
    - To describe the immune response to the FVIII transgene and AAV capsid proteins following systemic administration of AAV5-hFVIII-SQ
    - To assess the impact of BMN 270 on the frequency of FVIII replacement therapy during the study
    - To assess the impact of BMN 270 on the number of bleeding episodes requiring treatment during the study
    E.5.2.1Timepoint(s) of evaluation of this end point
    Immune responses will be assessed every week through Week 20, then every other week through Week 36, then once every 2 months until the end of the first year and then once every three months until the end of the study (in year 5).
    The impact of BMN 270 on the frequency of FVIII replacement therapy and number of bleeding episodes will be assessed at each visit by providing diaries to participants to record these events.
    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 Yes
    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) Yes
    E.7.1.1First administration to humans Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 concerned8
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    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 years6
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months0
    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 No
    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) No
    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 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 No
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    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)
    None
    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 Decision2015-06-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-05-08
    P. End of Trial
    P.End of Trial StatusOngoing
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-Wed Nov 21 09:28:39 GMT 2018 | 30 Churchill Place, Canary Wharf, London E14 5EU
    Legal notice
    EMA HMA