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    Summary
    EudraCT Number:2015-001824-43
    Sponsor's Protocol Code Number:DS1040-A-U103
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2017-03-15
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2015-001824-43
    A.3Full title of the trial
    A Phase 1b/2, multi-center, double-blind (principal investigators and study subjects blinded, sponsor unblinded), placebo-controlled, randomized, single-ascending dose study to assess the safety, pharmacokinetics, and pharmacodynamics of DS-1040B in subjects with acute ischemic stroke.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 1b/2 study to assess the safety, pharmacokinetics, and pharmacodynamics of DS-1040B in subjects with acute ischemic stroke.
    A.4.1Sponsor's protocol code numberDS1040-A-U103
    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 SponsorDaiichi Sankyo, 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 supportDaiichi Sankyo, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDaiichi Sankyo, Inc.
    B.5.2Functional name of contact pointClinical Trial Information Contact
    B.5.3 Address:
    B.5.3.1Street Address399 Thornall Street
    B.5.3.2Town/ cityEdison
    B.5.3.3Post codeNJ 08837
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1732590 5000
    B.5.5Fax number+1732906 5690
    B.5.6E-maileu_cta@dsi.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.3.1Product nameDS-1040b
    D.3.2Product code DS-1040b
    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 INNDS-1040B
    D.3.9.2Current sponsor codeDS-1040B
    D.3.9.3Other descriptive nameDS-1040B
    D.3.9.4EV Substance CodeSUB128772
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    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) 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 infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    DS-1040b is an inhibitor of the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa) intended to be used for the treatment of thrombotic diseases including acute ischemic stroke (AIS).
    E.1.1.1Medical condition in easily understood language
    Acute Ischemic Stroke
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level LLT
    E.1.2Classification code 10055221
    E.1.2Term Ischemic stroke
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the safety and tolerability of DS-1040b (IV infusion over 6 hours) in subjects with AIS within 4.5 to 12 hours after stroke symptom onset
    E.2.2Secondary objectives of the trial
    1. To assess plasma and urinary pharmacokinetics (PK) of DS-1040b in subjects with AIS.
    2. To assess the effect of DS-1040b on fibrinolysis biomarkers in subjects with AIS.
    3. To assess the effect of DS-1040b on recanalization at 24 hours in subjects with AIS and a visible occlusion demonstrated on brain imaging at predose.
    4. To assess the effect of DS-1040b on neurological outcome by using the National Institute of Health Stroke Scale (NIHSS) and functional outcome by using the modified Rankin Scale (mRS) in subjects with AIS.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subjects have a clinical diagnosis of acute ischemic stroke (including lacunar stroke) supported by computed topography or magnetic resonance imaging.
    2. Men and women 18 years of age and older.
    3. Subjects have stroke symptoms onset within 4.5 to 12 hours before initiation of study drug administration. For subjects with a wake-up stroke, symptoms onset time refers to the last time the subject was known to be well.
    4. Subjects have a NIHSS score of >2 .
    5. Subjects, (or their legally authorized representative -where applicable and based on country-specific practice), must give written informed consent to participate in the study prior to participating in any study-related procedures. A separate written informed consent is required for collecting a blood sample for genotyping.
    E.4Principal exclusion criteria
    1.Subjects have been treated or are anticipated to be treated with tissue plasminogen activator and/or endovascular thrombectomy during current stroke. Eligible subjects declining these treatments can be enrolled to this study.
    2. Subjects have evidence of intracranial hemorrhage on noncontrast computed tomography (CT) (or magnetic resonance [MR]).
    3. Subjects have symptoms of subarachnoid hemorrhage, even with normal CT.
    4. Subjects have an Alberta Stroke Program Early CT Score (ASPECTS) < 6.
    5. Subjects have prior non-traumatic intracranial haemorrhage(excluding microhemorrahages observed in imaging).
    6. Subjects have known arteriovenous malformation or aneurysm.
    7. Subjects have evidence of active bleeding.
    8. Subjects have platelet count < 100,000.
    9. Subjects have INR>1.7.
    10. Subjects have used unfractionated heparin within 24 hours prior to treatment and have an elevated partial thromboplastin time.
    11. Subjects have used a nonvitamin K antagonist oral anticoagulant such as dabigatran, rivaroxaban, apixaban, or other factor Xa inhibitors within 24 hours prior to treatment.
    12. Subjects have used fondaparinux or low molecular weight heparin at an anticoagulation dose within 24 hours prior to treatment.
    13. Subjects with anticipated use of an anticoagulation dose of heparin, or fondaparinux or low molecular weight heparin, or nonvitamin K antagonist oral anticoagulant such as dabigatran, rivaroxaban, apixaban, or other factor Xa inhibitors within 48 hours of randomization. Low dose heparin or low molecular weight heparin at a preventive dose are allowed from 24 hours after treatment start and after no intracranial bleeding has been confirmed on 24 hours repeat brain imaging.
    14. Subjects have blood pressure>185/110 mmHg, or require aggressive medication to maintain blood pressure below this limit (routine medical treatment is allowed to lower the blood pressure below this limit).
    15. Subjects have had intracranial surgery, clinically significant head trauma (in the opinion of Principal Investigator), Alteplase treatment, or a previous stroke within 1 month.
    16. Subjects have had major surgery within 14 days.
    17. Subjects have had gastrointestinal or genitourinary bleeding in the last 21 days.
    18. Subjects have had a lumbar puncture (or epidural steroid injection) within 14 days.
    19. Subjects have a preexisting disability classified by mRS>2.
    20. Subjects have an estimated glomerular filtration rate (using Modification of Diet in Renal Disease equation)<60 mL/min/1.73 m2.
    21. Subjects have baseline hemoglobin<10.5 g/dL.
    22. Subjects have a positive pregnancy test. Serum or urine pregnancy tests will be performed (according to site-specific practice) in women of childbearing potential (childbearing potential is assumed in women up to 55 years of age).
    23. Subject is currently participating in another investigational study or has participated in an investigational drug study within 30 days or 5 half-lives of that investigational drug prior to administration of the study drug.
    24. Subject is an employee or an immediate family member of an employee of the Sponsor, the CRO (INC Research), or the Site.
    25. Any other reason, in the opinion of the Investigator, which precludes subject participation in the study.
    E.5 End points
    E.5.1Primary end point(s)
    • Safety parameters:
    Safety parameters will include adverse events occurrence,physical examination findings, vital sign measurements, standard clinical laboratory parameters (including serum chemistry, hematology, urinalysis, and coagulation parameters), and electrocardiogram (ECG) parameters.
    Other safety parameters will include bleeding events and neurologic function. Bleeding events will be assessed and categorized as sICH, any intracranial hemorrhage (ICH), or non-ICH major bleeding. Neurologic function will be measured using the NIHSS.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 1, day 2, day 3, day 4, day 5 and at follow up (day 30 and day 90).
    E.5.2Secondary end point(s)
    • Pharmacokinetic parameters:
    Standard noncompartmental PK parameters will be assessed. Plasma samples for PK assessments will be taken at multiple timepoints in the study. Additionally, a PK sample may also be obtained outside of the specified timepoints during the study if deemed clinically necessary. Urine PK samples will also be collected and evaluated in the study.
    • Pharmacodynamic parameters:
    Pharmacodynamic analysis for TAFIa antigen and clot lysis along with D-dimer and total TAFIa activity will be performed. Remaining blood samples will be used for post-hoc TAFIa inhibition-related coagulation biomarker assessments.
    Recanalization will be assessed during the study.
    • Other parameters:
    An assessment of functional outcome using the mRS will be performed during the study.
    E.5.2.1Timepoint(s) of evaluation of this end point
    PK: Day 1, day 2, day 3, day 4 and day 5
    PD: Day 1, day 2 and day 3
    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 Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Information not present in EudraCT
    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
    Australia
    Canada
    Czech Republic
    France
    Germany
    Italy
    Korea, Republic of
    Slovakia
    Spain
    Taiwan
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    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 years2
    E.8.9.2In all countries concerned by the trial months6
    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: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 76
    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 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 state
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 16
    F.4.2.2In the whole clinical trial 96
    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 Decision2017-05-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-02-16
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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