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   43862   clinical trials with a EudraCT protocol, of which   7285   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:2015-002478-19
    Sponsor's Protocol Code Number:SHP616-300
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-12-23
    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 ConcernedGermany - PEI
    A.2EudraCT number2015-002478-19
    A.3Full title of the trial
    A Phase 3, Randomized, Double-blind, Placebo-controlled, Two-period, Three-sequence, Partial Crossover Study to Evaluate the Efficacy and Safety of Subcutaneous Administration of 2000 IU of C1 Esterase Inhibitor [Human] Liquid for Injection for the Prevention of Angioedema Attacks in Adolescents and Adults with Hereditary
    Angioedema
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to determine the efficacy and safety of C1 Esterase Inhibitor liquid for injection compared to placebo in the prevention of Angioedema attacks in adolescents and adults with hereditary angioedema.
    A.4.1Sponsor's protocol code numberSHP616-300
    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 SponsorShire ViroPharma, 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 supportShire ViroPharma, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationShire ViroPharma, Inc.
    B.5.2Functional name of contact pointHoward Mayer
    B.5.3 Address:
    B.5.3.1Street Address300 Shire Way
    B.5.3.2Town/ cityLexington
    B.5.3.3Post codeMA 02421
    B.5.3.4CountryUnited States
    B.5.4Telephone number0017814829909
    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.3.1Product nameC1 esterase inhibitor liquid for injection
    D.3.2Product code SHP616
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNC1 Esterase Inhibitor (human)
    D.3.9.3Other descriptive nameCOMPLEMENT C1 ESTERASE INHIBITOR
    D.3.9.4EV Substance CodeSUB22696
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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 Yes
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    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.IMP: 2
    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 Firazyr
    D.2.1.1.2Name of the Marketing Authorisation holderShire Orphan Therapies GmbH
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/03/133
    D.3 Description of the IMP
    D.3.4Pharmaceutical form 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 INNICATIBANT
    D.3.9.1CAS number 130308-48-4
    D.3.9.4EV Substance CodeSUB08104MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 No
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    hereditary angioedema
    E.1.1.1Medical condition in easily understood language
    Swelling and/or painful attacks in teenagers and adults with Hereditary Angioedema (HAE).

    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10019860
    E.1.2Term Hereditary angioedema
    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
    The primary objective of this study is to demonstrate superior efficacy of SC administration of 2000 IU C1 esterase inhibitor [human] liquid for injection for the prevention of angioedema attacks relative to placebo based on the normalized number of attacks (NNA) during a treatment period.
    E.2.2Secondary objectives of the trial
    The key secondary objective is to demonstrate the superior efficacy of SC administration of 2000 IU C1 esterase inhibitor [human] liquid for injection for the prevention of angioedema attacks relative to placebo as measured by the proportion of subjects meeting the criterion of at least 50% reduction in the NNA during the 2000 IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period:
    1. The proportion of subjects meeting the criterion of at least a 50% reduction in the NNA during the 2000 IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period.
    2. The NNA during each treatment period excluding the first 2 weeks.
    3. The proportion of subjects meeting the criterion of at least a 50% reduction in the NNA for the 2000IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period excluding the first 2 weeks of each treatment period.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Be ≥12 years of age, or in Germany and Israel, be ≥18 years of age.
    2. Have a diagnosis of HAE (Type I or II) and a functional C1 INH level less than 50% of normal.
    3. Meet one of the following criteria (attack rate may be based on subject recall in conjunction with the subject’s medical records):
    a. If subject is adult (>18 years of age) and currently receiving prophylactic therapy with C1 INH, have a history of ≥2.0 angioedema attacks per month (average) during the 3 consecutive months prior to starting prevention therapy.
    OR
    b. If subject is adolescent (>12 and <18 years of age) or adult and not receiving
    prophylactic therapy with C1 INH, have a history of ≥2.0 angioedema attacks
    per month (average) during the 3 consecutive months prior to the screening
    visit.
    OR
    c. If subject is adult (>18 years of age) and currently receiving a stable dose of
    attenuated androgens, have a history of ≥2.0 angioedema attacks per month
    (average) during the 3 consecutive months prior to the screening visit.
    4. For subjects ≥18 years of age, be willing to receive treatment with icatibant for any angioedema attacks that occur during the study that, in the opinion of the healthcare care provider, require medical intervention. Note: For subjects ≥12 to <18 years of age, standard of care therapy per local protocols should be provided.
    5. Agree to adhere to the protocol-defined schedule of assessments.
    6. If female, must have a negative serum beta human chorionic gonadotrophin (β-hCG) pregnancy test at the screening visit and must have a negative urine pregnancy test prior to the first dose of investigational product (Visit 1a), and agree to comply with any applicable contraceptive requirements of the protocol.
    7. If male, be surgically sterile or agree to follow an acceptable method of birth control (eg, abstinence, barrier control) from the screening visit through 2 months after the last dose of investigational product.
    8. If an adult (≥18 years of age), be informed of the nature of the study and provide written informed consent before any study-specific procedures.
    OR
    If a child (<18 years of age), have a parent(s)/legal guardian who is informed of the nature of the study provide written informed consent for the child to participate in the study before any study-specific procedures are performed (with assent from the child when appropriate). Alternatively, certain sites/Independent Reviewing Authorities may permit adolescents who are <18 years of age to be informed of the nature of the study and provide written informed consent without consent from a parent(s)/legal guardian.
    E.4Principal exclusion criteria
    1. Adults (>18 years of age) receiving prophylactic IV CINRYZE that exceeds the approved dosing regimen of 1000 U every 3 or 4 days (receiving a weekly dose >2000 U).
    2. Adolescents (>12 and <18 years of age) currently receiving prophylactic therapy with C1 INH (not applicable to Germany and Israel).
    3. Have had signs or symptoms of an angioedema attack within 2 days prior to the first dose of investigational product in Treatment Period 1.
    4. Have received any C1 INH therapy or any blood product for the treatment or prevention of angioedema attacks within 3 calendar days prior to the first dose of investigational product in Treatment Period 1.
    5. If female, have started or changed the dose of any hormonal contraceptive regimen or hormone replacement therapy (ie, estrogen/progestin containing products) within 2 months prior to the screening visit.
    6. Have a history of hypercoagulability (abnormal blood clotting) or other predisposition for thromboembolism.
    7. Have a diagnosis of acquired angioedema or known presence of anti-C1 INH antibodies.
    8. Have a history of allergic reaction to C1 INH products, including CINRYZE (or any components of CINRYZE), or other blood products, or FIRAZYR (icatibant).
    9. Be pregnant or breastfeeding.
    10. Have received an investigational drug within 30 days prior to the first dose of investigational product in Treatment Period 1.
    11. Have, as determined by the investigator and/or the sponsor’s medical monitor, any surgical or medical condition (including positive for hepatitis B, hepatitis C, or HIV infection; alcohol, drug, or medication abuse within 1 year before screening; or mental condition rendering the subject or parent(s)/legal guardian unable to understand the nature, scope of the study, and possible consequences of the study), or relationship to study staff or sponsor (including people accommodated in an institution as well as people who are dependent on the sponsor, CRO, site or the investigator) that could interfere with the administration of investigational product or interpretation of study results.
    E.5 End points
    E.5.1Primary end point(s)
    The normalized number of attacks (NNA) recorded during each treatment period. The NNA is computed as the number of attacks per month (ie, 30.4 days) of exposure (NNA = 30.4 x [number of attacks during treatment period]/[days of treatment period]). If a subject discontinues during the treatment period, the denominator of the NNA will be the days on treatment for that subject; this is equivalent to the last observation carried forward imputation method to impute the missing information following the subject’s discontinuation
    E.5.1.1Timepoint(s) of evaluation of this end point
    14 weeks
    E.5.2Secondary end point(s)
    Key Secondary Efficacy Endpoints:
    1. The proportion of subjects meeting the criterion of at least a 50% reduction in the NNA during the 2000 IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period.
    2. The NNA excluding the first 2 weeks of each treatment period
    3. The proportion of subjects meeting the criterion of at least 50% reduction in the NNA for the 2000 IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period excluding the first 2 weeks of each treatment period.
    Key secondary endpoints 1 and 3 are defined as achieving a ≥ 50% reduction in the NNA (PR) during the 2000 IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period.
    The Key secondary endpoints 1 and 3 will be analyzed as the proportion of subjects meeting criterion PR. The null hypothesis is that PR is less than or equal to 0.2 and the alternative hypothesis is that PR is greater than 0.2. The proportion meeting criterion PR will be estimated with an exact 95% CI. The lower limit of the 95% CI for the proportion will be compared with 0.2.
    Analysis of key secondary endpoint 2 will follow the same method (ie, the linear mixed effect model) used for the primary efficacy endpoint.
    E.5.2.1Timepoint(s) of evaluation of this end point
    14 weeks
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy No
    E.6.4Safety Yes
    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) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    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
    Canada
    Germany
    Hungary
    Israel
    Romania
    Spain
    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
    Last patient last visit
    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 months3
    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 months3
    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 Yes
    F.1.1Number of subjects for this age range: 16
    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: 16
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 33
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 17
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Children below the age of 18 years (Only provide assent)
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state17
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 66
    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 resume their standard of care therapy after they have completed the 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 Decision2016-06-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-06-28
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-07-24
    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-Fri Apr 26 11:29:59 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA