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:2017-000373-36
    Sponsor's Protocol Code Number:997HA402
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2017-10-05
    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 ConcernedFrance - ANSM
    A.2EudraCT number2017-000373-36
    A.3Full title of the trial
    A Non-controlled, Open-Label, Multicenter, Study of Efficacy of rFVIIIFc for Immune Tolerance Induction (ITI) in Severe Hemophilia A Subjects with Inhibitors Undergoing the First ITI Treatment
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical study exploring the use of rFVIIIFc in patients with severe Haemophilia A who are undergoing Immune Tolerance Induction (ITI) for the first time
    A.4.1Sponsor's protocol code number997HA402
    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 SponsorBioverativ 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 supportBioverativ Therapeutics Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBioverativ Therapeutics Inc.
    B.5.2Functional name of contact pointN/A
    B.5.3 Address:
    B.5.3.1Street Address225 Second Avenue
    B.5.3.2Town/ cityWaltham, MA
    B.5.3.3Post code02451
    B.5.3.4CountryUnited States
    B.5.6E-mailclinicaltrials@bioverativ.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 Yes
    D.2.1.1.1Trade name ELOCTA
    D.2.1.1.2Name of the Marketing Authorisation holderSwedish Orphan Biovitrum AB (publ)
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.1Product namerecombinant Factor VIII Fc
    D.3.2Product code rFVIIIFc
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    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 INNEFMOROCTOCOG ALFA
    D.3.9.1CAS number NA
    D.3.9.2Current sponsor codeBIIB031
    D.3.9.3Other descriptive namerFVIIIFc, recombinant Factor FVIII Fc
    D.3.9.4EV Substance CodeSUB168409
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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) Yes
    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 Yes
    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
    Hemophilia A
    E.1.1.1Medical condition in easily understood language
    Hemophilia A is a genetic disorder that impairs the body's ability to control blood clotting or coagulation, which is used to stop bleeding.
    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 20.0
    E.1.2Level LLT
    E.1.2Classification code 10060613
    E.1.2Term Hemophilia A (Factor VIII)
    E.1.2System Organ Class 100000011915
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10053751
    E.1.2Term Hemophilia A with anti factor VIII
    E.1.2System Organ Class 100000011928
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to describe the time to tolerance with rFVIIIFc in subjects within a maximum of 12 months ITI treatment.
    E.2.2Secondary objectives of the trial
    •To describe the outcome of ITI treatment
    •To describe the relapse rate over the 48-week period following successful ITI performed with rFVIIIFc
    •To describe the intercurrent bleeding during ITI and during the 48-week period after successful ITI performed with rFVIIIFc
    •To describe safety and tolerability of rFVIIIFc when used for ITI
    •To evaluate the impact of ITI treatment with rFVIIIFc on health economics and adherence
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Ability of the subject or his legally authorized representative (e.g., parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations.
    2.Male subjects of any age diagnosed with severe hemophilia A (as confirmed from the medical record).
    3.Diagnosed with high titer inhibitors (historical peak ≥5 BU/mL, according to medical records)
    4.Previously treated with any plasma-derived or recombinant conventional or Extended Half-Life FVIII.
    E.4Principal exclusion criteria
    1. Other coagulation disorder(s) in addition to hemophilia A.
    2. Previous ITI
    3. History of hypersensitivity or anaphylaxis associated with any rFVIIIFc administration.
    4. Planned major surgery to be deferred after study completion (minor surgery such as tooth extraction or insertion-replacement of central venous access device is allowed)
    5. Abnormal renal function (serum creatinine >2.0 mg/dL) as assessed by local laboratory.
    6. Serum alanine aminotransferase or aspartate aminotransferase >5 × upper limit of normal (ULN) as assessed by local laboratory.
    7. Serum total bilirubin >3 × ULN as assessed by local laboratory
    8. Previous registration in this study.
    9. Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 30 days (or 5 half-lives of the agent, whichever is longer) prior to the Baseline Visit.
    10. Inability to comply with study requirements.
    11. Presence of any medical or psychological condition or laboratory result that in the opinion of the Investigator can interfere with the subject's ability to comply with the protocol requirements or makes the subject not appropriate for inclusion to the study and treatment with Elocta/Eloctate.
    12. Other unspecified reasons that, in the opinion of the Investigator or Bioverativ, make the subject unsuitable for enrollment.
    13. Unwillingness or inability to comply with the requirements of the protocol, including the presence of any condition (physical, mental, or social) that prevents the subject from participating in visits as scheduled
    14. Concurrent systemic treatment with immunosuppressive drugs within 12 weeks prior to Screening. Exceptions to this include: ribavirin for treatment of hepatitis C virus (HCV), and/or systemic steroids (a total of 2 courses of pulse treatments lasting no more than 7 days within 12 weeks prior to Day 1) and/or inhaled steroids
    The following criteria refer to tests performed within 26 weeks prior to Screening. If not available, a new test should be drawn at the Screening visit.
    15. Cluster of differentiation 4 (CD4) lymphocytes >200 mm3 at Screening, if known as human immunodeficiency virus (HIV) antibody positive based on medical history or HIV testing
    16. Viral load of <400 copies/mL at Screening, if known HIV antibody positive, based on medical history.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study is time to tolerization with a maximum of 12 months ITI treatment offered in the study. (Tolerization defined as inhibitor titer <0.6BU/ml, FVIII recovery > 66% and t1/2 of ≥7hrs)
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoint of time to tolerization will be summarized descriptively using minimum, mean, standard deviation, median, 25th and 75th quartiles, and maximum. A Kaplan-Meier plot showing percentage of subjects who are tolerized against time from the first ITI infusion will also be generated. Subjects not achieving ITI success during the 12 months ITI period will be censored at the last observed time for this analysis. The ITIFAS analysis set will be used for this analysis
    E.5.2Secondary end point(s)
    •ITI success
    oNegative titer for inhibitor (<0.6 BU/mL by the Nijmegen-modified Bethesda assay) in 2 consecutive determinations
    oFVIII incremental recovery (IR) >1.3 IU/dL per IU/kg in 2 consecutive determinations representing 66% of the expected IR 2 IU/dL per IU/kg (ref SmPC).
    oFVIII t1/2 ≥7 hours
    •Occurrence of relapse during a 48-week period following successful ITI treatment (defined as inhibitor titer >0.6 BU/mL or abnormal recovery after tolerance is achieved)
    •Number of bleeding episodes during ITI and during the 48-week period after successful ITI performed with rFVIIIFc
    •Treatment emergent adverse events (TEAE) and treatment emergent serious adverse events (TESAE)
    •Number of days away from work or school
    •Number of hospitalization days
    •Adherence (defined as percentage of administered doses versus planned doses)
    •Consumption of rFVIIIFc (measured in total rFVIIIFc use)
    E.5.2.1Timepoint(s) of evaluation of this end point
    After Baseline Visit which is the start of ITI treatment, subjects will be seen at Week 2 and every fourth week until subjects acheive a negative inhibitor titer (<0.6 BU/mL). Starting at time of first negative inhibitor titer until ITI success OR 48 weeks of treatment, subjects will be seen every 2nd week. With ITI success (3 success criteria met) and continuing for 16 weeks (Tapering period), subjects will have assessment visits after 2 weeks, 4 weeks and then every 4th week thereafter. Follow-up Period constitutes the time period in which subject returns to prophylactic dosing regimen and will be approximately 32 weeks in duration.
    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 No
    E.6.4Safety No
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    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.8.2.4Number of treatment arms in the trial1
    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.8.4.1Number 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 EEA12
    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
    Belgium
    Canada
    European Union
    France
    Germany
    Italy
    Japan
    Puerto Rico
    Spain
    United Kingdom
    United States
    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
    The end of study is last subject, last visit for final collection of data.
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    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: 30
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 27
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 2
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 1
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    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
    Parents/legal guardians of subjects must be provided with the informed consent information prior to the Screening Visit to allow adequate time for review and an opportunity to discuss the study with the Investigator/designee.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state1
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 12
    F.4.2.2In the whole clinical trial 30
    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 Decision2017-09-25
    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 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-Sun May 05 00:39:21 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA