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    The EU Clinical Trials Register currently displays   43874   clinical trials with a EudraCT protocol, of which   7294   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).

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    Summary
    EudraCT Number:2007-002035-81
    Sponsor's Protocol Code Number:2-001
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-10-31
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2007-002035-81
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study to Assess the Safety and Efficacy Effects of ART-123 on Subjects with Sepsis and Disseminated Intravascular Coagulation
    A.4.1Sponsor's protocol code number2-001
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorArtisan Pharma, 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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameART-123
    D.3.2Product code ART-123
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNThrombomodulin alfa
    D.3.9.1CAS number 120313-91-9
    D.3.9.2Current sponsor codeART-123
    D.3.9.3Other descriptive nameRecombinant, soluble, human thrombomodulin
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6.0
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 Yes
    D.3.11.13.1Other medicinal product typeRecombinant.
    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 placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Sepsis and disseminated intravascular coagulation.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10040047
    E.1.2Term Sepsis
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10013442
    E.1.2Term Disseminated intravascular coagulation
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the safety and activity of ART-123 in reducing mortality in subjects with sepsis and disseminated intravascular coagulation
    E.2.2Secondary objectives of the trial
    To assess the efficacy of ART-123 in resolution of DIC in this population
    To establish the predictive value of a DIC score based on platelet count and INR compared with the ISTH DIC score.
    To evaluate several coagulation parameters in predicting response to ART-123
    To obtain an accurate estimate of the risk of death in subjects with DIC and sepsis.
    To assess the safety of ART-123 in subjects with sepsis and DIC.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    To be included in the study, subjects must have infection or suspected
    infection and must be treated with antimicrobial medication(s) for this
    specific infection. Additionally, a modified ISTH DIC score of ≥2
    related to infection/sepsis using the platelet count and/or INR result plus the presence of at least 2 out of 4 sepsis related SIRS criteria as described below are required.

    Once the subject presents with an eligible modified DIC score (2 or
    greater), he/she must have ≥2 sepsis related SIRS criteria within the 24
    hours prior to obtaining the eligible DIC score. One of the 2 SIRS criteria must be either temperature criterion or the WBC criterion. Subjects who met SIRS
    criteria for reasons other than sepsis in the days prior to the current septic
    episode may be eligible The four SIRS criteria for the purposes of inclusion into this
    trial are described as the following:
    • Temperature >38ºC or <36ºC (core temperature for low
    range temperature)
    • Heart Rate >90 BPM (unless the subject is treated with β-
    blockers or heart rate is pacemaker dependent. In these
    cases, only 1 other SIRS criterion, either temperature or the WBC is required)
    • Respiratory Rate >20 BPM or PaCO2<32 mmHg or
    mechanically ventilated subject
    • WBC >12,000 or <4,000 cells/μL or >10% Band forms

    If a single INR test or platelet count qualifies the patient, the diagnosis of modified DIC is made the first time such abnormal test is obtained. To use a combination of INR and Platelet count results to meet the modified DIC score of greater than or equal to 2, these two tests must be performed no more than 24 hours apart. The time the latter test is obtained is the time of diagnosis of modified DIC. Regardless if one test qualifies the patient for enrollment, both INR and platelet count must be obtained at screening and documented in the eCRF.

    Once the patient meets criteria of DIC, a maximum of 36 hours is allowed for consent, randomization and administration of study drug.

    Platelet count (x 10^3/mm^3):
    ≥150 = 0 points
    ≥120-<150 = 1 point
    ≥80-<120 = 2 points
    <80 = 3 points

    Prothrombin time INR:
    ≤ 1.2 = 0 points
    >1.2-1.4 = 1 point
    >1.4-1.6 = 2 points
    >1.6 = 3 points
    E.4Principal exclusion criteria
    Subjects to be excluded from the study are those who meet any of the criteria below:
    General
    1.Unable to provide informed consent, or lack of consent from an acceptable surrogate in the event that the subject is incapable of providing consent
    2.Women who are pregnant or breastfeeding or intend to get pregnant within 28 days of enrolling into the study
    3.Subjects < 18 years of age
    4.Allergy to ART-123 or any components of the drug product
    5.Subjects unwilling to allow transfusion of blood or blood products
    6.Presence of an advance directive to withhold life-sustaining treatment, with the exception of cardiopulmonary resuscitation (CPR)
    7.Subjects not in a hospital ward or unit with continuous and closely monitored health care that is provided to critically ill subjects (i.e. an Intensive Care Unit, or monitored bed unit with a high nurse to subject ratio 1:2 or 1:3) or in process of being admitted to one
    8.Previous treatment with ART-123
    9.Subjects who met inclusion/exclusion criteria more than 36 hours prior to randomization
    10.Subjects whose INR and platelet count abnormalities improve such that they no longer meet inclusion criteria
    11. Subjects whose body weight is ≥ 175kg

    Medical Conditions
    1.Known conditions that could confound the diagnosis of DIC due to sepsis (see protocol for details)
    2.Known conditions that increase the risk of bleeding (see protocol for details)
    3.Known medical condition associated with a hypercoagulable state (see protocol for details)
    4.Known or suspected severe liver disease (see protocol for details)
    5.History of solid organ (excluding uncomplicated kidney), bone marrow or stem cell transplantation
    6.Acute pancreatitis with no established source of infection
    7.Severe renal failure characterized by
    a.chronic renal failure on either hemodialysis, hemofiltration or peritoneal dialysis
    b.need for acute dialysis

    Concomitant Medications
    1.Intended use of Xigris® (drotrecogin alfa [activated]) by treating physician
    2. All anticoagulants, antiplatelet agents, antithrombotics and thrombolytics are excluded except:
    a. Heparin locks/flushes
    b. DVT Prophylaxis with either unfractionated heparin doses no higher than 10000 U SQ within a 24 hour period or with LMWH no higher than recommended prophylactic dose range. However, no switching or alternating between unfractionated heparin and LMWH is allowed during the treatment with study drug and up to Day 14

    Laboratory Values
    1.Platelet count <20,000 OR platelet count <30,000 after platelet transfusion.

    Prognostic Assessment
    1.Subject’s family, physician, or both not in favor of aggressive treatment of subject or presence of an advance directive to withhold life-sustaining treatment (excluding CPR)
    2.Subjects who are likely to have limitations put on their life support, given their preexisting, uncorrectable medical condition or who are not expected to survive 90 days due to their underlying medical condition. This would include subjects with, or suspected to have:
    a.Poorly controlled neoplasms or subjects currently receiving chemotherapy
    b.New York Heart Association class IV subjects
    c.Prior cardiac arrest requiring CPR without fully demonstrated neurological recovery, or subject with imminent death
    d.Vascular disease resulting in severe exercise restriction (i.e., unable to climb stairs or perform household duties), or chronic restrictive or obstructive pulmonary disease that also results in severe exercise restriction, or documented chronic hypoxia, hypercapnia, secondary polycythemia, severe pulmonary hypertension (mean pulmonary pressure >40 mm Hg) or respirator dependency
    e.End-stage neurological disorders (e.g., amyotrophic lateral sclerosis - Lou Gehrig's disease)
    3.Participation in another investigational study within 30 days before randomization
    4.In the Investigator’s opinion the subject should not participate in the trial
    5.A woman of childbearing potential who does not agree to use a medically acceptable form of contraception for the duration of the trial (28 days or 22 days post the last dose of study drug administration). Medically acceptable forms of contraception include:
    a.Contraceptive Medication
    b.Intrauterine Device
    c.Double Barrier Methods
    d.Tubal Ligation
    E.5 End points
    E.5.1Primary end point(s)
    The primary analysis will test the difference in the 28-day all-cause mortality rates between treatment groups in the ITT population. The rates will be estimated from the product-limit (Kaplan-Meier) with an asymptotic variance determined from Greenwood’s formula. Missing data will be censored
    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 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 Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    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 Yes
    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.8.3 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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA65
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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
    The last patient's 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 months7
    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 months7
    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 Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Yes
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Many subjects who will be eligible for this protocol will not be able to give fully informed consent themselves due to various reasons including sedation, or being in an unconscious state.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 490
    F.4.2.2In the whole clinical trial 800
    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)
    Normal treatment for the patient's condition will continue after 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 Decision2007-07-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-10-18
    P. End of Trial
    P.End of Trial StatusCompleted
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    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
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