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   43871   clinical trials with a EudraCT protocol, of which   7290   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:2015-001486-67
    Sponsor's Protocol Code Number:101HEMB01
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2016-03-14
    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 ConcernedBulgarian Drug Agency
    A.2EudraCT number2015-001486-67
    A.3Full title of the trial
    A Phase I/II Open-Label Safety and Dose-Finding Study of Adeno-Associated Virus (AAV) rh10-Mediated Gene Transfer of Human Factor IX in Adults With Moderate/Severe to Severe Hemophilia B
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An early-phase clinical study of a virus that transfers the gene for human coagulation factor IX in adults with moderate/severe to severe inherited coagulations defects
    A.4.1Sponsor's protocol code number101HEMB01
    A.5.4Other Identifiers
    Name:IND NumberNumber:16543
    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 SponsorDimension Therapeutics, 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 supportDimension Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDimension Therapeutics, Inc.
    B.5.2Functional name of contact pointClinical Development
    B.5.3 Address:
    B.5.3.1Street Address840 Memorial Drive
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02139
    B.5.3.4CountryUnited States
    B.5.6E-mailallen.poma@dimensiontx.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code DTX101
    D.3.4Pharmaceutical form Concentrate for 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 INNNot yet assigned
    D.3.9.3Other descriptive nameDTX101
    D.3.9.4EV Substance CodeSUB180345
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number3000000000000
    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 numberClassified as gene therapy medicinal product, EMA/CAT/419942/2015
    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
    Moderate/severe to severe hemophilia B
    E.1.1.1Medical condition in easily understood language
    Moderate/severe to severe inherited blood coagulation disorder
    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 10060614
    E.1.2Term Hemophilia B (Factor IX)
    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 determine the safety of single ascending intravenous (IV) doses of DTX101 in adults with moderate/severe to severe hemophilia B.

    - To establish a dose of DTX101 that achieves a peak plasma level of vector-derived factor IX (FIX) at 6 weeks after IV administration to allow further clinical development.
    E.2.2Secondary objectives of the trial
    Secondary:
    - To assess the impact of DTX101 on the number of bleeding episodes requiring recombinant FIX infusion during the study.

    - To evaluate the kinetics, duration, and magnitude of plasma FIX activity, by dose, after IV
    administration of DTX101 in adults with hemophilia B.

    - To assess the impact of DTX101 on the frequency of FIX replacement therapy during the study.

    - To describe the immune response to the FIX transgene after IV administration of DTX101.

    - To assess the impact of DTX101 on the subject’s quality of life.

    Exploratory:
    - To describe the immune response to AAVrh10 capsid proteins after IV administration of DTX101.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male ≥18 years of age.
    2. Moderate/severe or severe hemophilia B (baseline FIX activity ≤2% of normal or documented history of FIX activity ≤2%).
    3. At least 3 bleeding episodes per year that require on-demand treatment with FIX OR are treated with a prophylactic regimen of FIX.
    4. At least 100 days exposure history to FIX.
    5. No documented history of inhibitors (neutralizing antibodies) to exogenous FIX.
    6. No known allergic reaction to exogenous FIX or any component of DTX101.
    7. Willing to stop prophylactic treatment with recombinant FIX at specified time points during the study.
    8. Willing and able to provide written informed consent.
    9. Willing and able to comply with study procedures and requirements.
    10. Willing to use effective contraception at the time of administration of DTX101 and for 3 months following administration of DTX101. Appropriate contraceptive methods include a condom with spermicide. Abstinence, defined as sexual inactivity, is an acceptable form of birth control; however, appropriate contraception must be used if the subject becomes sexually active.
    E.4Principal exclusion criteria
    1. History of liver disease as evidenced by any of the following: portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy, or a liver biopsy with evidence of stage 3 fibrosis.
    2. Significant hepatic inflammation or cirrhosis as evidenced by any of the following: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.0 × upper limit of normal (ULN), total bilirubin >1.5 × ULN, alkaline phosphatase (ALP) >2.5 × ULN, platelet count <75,000 cells/μL, and prothrombin time (PT) or international normalized ratio (INR) >1.5 × ULN.
    3. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, documented by current use of antiviral therapy for HBV or HCV or by hepatitis B surface antigen (HBsAg) or HCV RNA positivity. NOTE: Two negative viral assays by polymerase chain reaction (PCR), collected at least 6 months apart, will be required to be considered negative for HCV. Subjects can be rescreened once if they have one negative sample and must wait to have the second sample collected within the following 6 months.
    4. History of human immunodeficiency virus (HIV) infection AND any of the following: CD4+ cell count <350 cells/mm3, change in antiretroviral therapy regimen within 6 months prior to Day 0, or plasma viral load >200 copies/mL, on 2 separate occasions, as measured by PCR.
    5. Anti-AAVrh10 neutralizing antibody titer >1:5.
    6. Participation (current or previous) in another gene therapy study.
    7. Participation in another investigational medicine study within 3 months before screening.
    8. History of a malignancy for which the subject has received treatment in the past 2 years except for prostate cancer treated with watchful waiting or surgically removed non-melanoma skin cancer.
    9. Has any other significant medical condition that the investigator feels would be a risk to the subject or would impede the study.
    E.5 End points
    E.5.1Primary end point(s)
    1. The incidence of adverse events (AEs), treatment-emergent AEs (TEAEs), and serious AEs (SAEs) will be summarized for each dosing cohort by severity and relationship to study product.
    2. The change from baseline in FIX activity at Week 6 as determined by the activated partial thromboplastin time (aPTT) clot-based assay.
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. from the time the subject signs the ICF until their exit from the study
    2. Week 6
    E.5.2Secondary end point(s)
    Secondary endpoints:
    1. The annualized bleeding rate (ABR) will be calculated for all subjects through Week 52 (±1 week).
    2. The time course of FIX activity, as determined by aPTT, will be summarized by time point and dose level of DTX101.
    3. The annualized and average weekly use of FIX replacement therapy will be calculated for all subjects through Week 52 (±1 week).
    4. The development of neutralizing antibodies to FIX (FIX inhibitor), as determined by a Bethesda assay, will be summarized by time point and dose level of DTX101.
    5. The development of a cell-mediated immune response to FIX, as determined by enzyme-linked immunospot (ELISPOT) assay, will be summarized by time point and dose level of DTX101.
    6. Responses to the EuroQol 5D 5 level (EQ-5D-5L™) and Haemophilia-Specific Quality of Life (Haem-A-QoL) will be summarized.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Through Week 52 (±1 week)
    2. At screening; Day 0 predose; Weeks 2, 4, 6, 8, 10, 12; once every four weeks from Week 16 to Week 52
    3. Through Week 52 (±1 week)
    4. At screening; Day 0 predose; Weeks 6, 8, 16, 32, 40, 48, 52
    5. Day 0 predose; Weeks 6, 8, 16, 32, 40, 48, 52
    6. Day 0 predose; Weeks 24, 36, 48 and 52
    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 Yes
    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 concerned1
    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
    Bulgaria
    France
    Italy
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    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 years1
    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 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: 13
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    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 state5
    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 patients have ended their participation in the trial, they will be treated according to the normal standard of care. After completion of this study, subjects will be offered enrollment into an extension study to evaluate the long-term safety and effect of DTX101 on clinical outcome measures.
    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 Decision2016-04-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-04-05
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2017-10-18
    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-Sun May 05 08:57:06 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA