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    Summary
    EudraCT Number:2014-002481-78
    Sponsor's Protocol Code Number:EBI-EA230-LPS-2014
    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:2014-09-30
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2014-002481-78
    A.3Full title of the trial
    Randomized double blind placebo-controlled clinical safety, tolerability and pharmacokinetic/-dynamic study on the effects of escalating single intravenous doses of EA-230 on the innate immune response during experimental human endotoxemia
    Gerandomiseerd dubbel blind placebo-gecontrolleerd klinisch veiligheid, tolerantie, farmacokinetisch en farmacodynamisch onderzoek naar het effect van continue intraveneuze doses van EA-230 op het aangeboren immuunsysteem tijdens experimentele humane endotoxinemie.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The effect of EA-230 on the immuneresponse
    Het effect van EA-230 op de immuunrespons
    A.3.2Name or abbreviated title of the trial where available
    PK/PD of EA-230 during endotoxemia
    PK/PD van EA-230 tijdens endotoxinemie
    A.4.1Sponsor's protocol code numberEBI-EA230-LPS-2014
    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 SponsorExponential Biotherapies Inc
    B.1.3.4CountryNetherlands
    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 supportExponential Biotherapies Inc.
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationRadboud UMC, Research Intensive care
    B.5.2Functional name of contact pointLucas van Eijk
    B.5.3 Address:
    B.5.3.1Street AddressP.O. Box 9101, internal adres 710
    B.5.3.2Town/ cityNijmegen
    B.5.3.3Post code6500HB
    B.5.3.4CountryNetherlands
    B.5.6E-maillucas.vanEijk@radboudumc.nl
    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 New pharmaceutical compound. The answer on section D2.1 should be "no". But due to persisting error in the form, this answer could not be entered. This error had been notified to the service desk of ema, without satisfactory result.
    D.2.1.1.2Name of the Marketing Authorisation holder-
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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 nameEA-230
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.11 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 Yes
    D.3.11.13.1Other medicinal product typeEA-230 is a linear tetramer peptide with the sequence AQGV. A family of small peptides related to the core loop-2 region of the B-chain of hCG. EA-230 is manufactured by chemical synthesis.
    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 placeboInfusion
    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
    Systemic inflammatory respons (SIRS) and associated acute kidney injury (AKI)
    systemische inflammatoire respons (SIRS) en daaraan gerelateerde acute nierschade
    E.1.1.1Medical condition in easily understood language
    inflammatory response and kidney damage
    Ontstekingsreactie en nier schade
    E.1.1.2Therapeutic area Body processes [G] - Immune system processes [G12]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part 1: To assess the safety, tolerability and pharmacokinetic-dynamic response, of single escalating doses of EA-230 in healthy subjects.

    Part 2: To assess the dose-and plasma concentration-response relation of single escalating doses EA-230 on inflammation and LPS-induced changes in markers for renal function, and to assess safety, tolerability and PK of EA-230 under the condition of experimental endotoxemia.
    Deel 1: het vaststellen van de veiligheid, tolerantie en pharmacokinetische en dynamische repsons van een constante toediening van EA-230 in gezonde proefpersonen.

    Deel 2: het vaststellen van de dosis en plasma gerelateerde relatie van een constante toediening van EA-230 op de LPS-geinduceerde systemische ontstekengsreactie.
    E.2.2Secondary objectives of the trial
    Modulation by EA-230 on markers of inflammation-induced kidney injury and changes in renal function
    Modulerend effect van EA-230 op markers van ontsteking-geinduceerde nier schade en de nierfunctie
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Written informed consent to participate in this trial prior to any study-mandated procedure.
    2.Subjects aged 18 to 35 years inclusive, for part 2 only male subjects will be included.
    3.Subjects and their partners have to agree to use a reliable way of contraception from study entry until 3 months after study drug administration.
    4.BMI between 18 and 30 kg/m², with a lower limit of body weight of 50 kg
    5.Healthy as determined by medical history, physical examination, vital signs, 12 lead electrocardiogram, and clinical laboratory parameters
    6.Negative results for hard drug use from urine drug screen at screening
    1.Geschreven informed consent om deel te nemen aan de trial vóór elke studie verplichte procedure.
    2.proefpersonen met een leeftijd tussen 18 en 35 jaar, voor het tweede gedeelte van de studie alleen mannelijke proefpersonen
    3.prefpersonen en hun partners stemmen in met een betrouwbare manier van anti-conceptie gedurende de start van de studie tot 3 maanden na de toediening van studie-medicijn toediening.
    4.BMI tussen 18 en 30 kg/m², met een lichamsgewicht ondergrens van 50kg
    5.Gezond verklaard, vastgesteld aan de hand van medische voorgeschiedenis, medisch lichamelijk onderzoek, vitale parameters, 12-afleidings electrocardiogram en klinische lab waardes
    6.Negatief testresultaat voor hard drugs gebruik uit de urinescreening tijdens het screeningonderzoek.
    E.4Principal exclusion criteria
    1.Unwillingness to abstain from any medication, recreational drugs or anti-oxidant vitamin supplements during the course of the study and within 7 days prior to study Day 1.
    2.Unwillingness to abstain from nicotine, or alcohol or within 1 day prior to study Day 1
    3.Previous participation in a trial where LPS was administered
    4.Surgery or trauma with significant blood loss or blood donation within 3 months prior to studyDay 1
    5.History, signs or symptoms of cardiovascular disease, in particular:
    • History of frequent vaso-vagal collapse or of orthostatic hypotension
    • Resting pulse rate ≤45 or ≥100 beats / min
    • Hypertension (RR systolic >160 or RR diastolic >90)
    • Hypotension (RR systolic <100 or RR diastolic <50)
    • conduction abnormalities on the ECG consisting of a 1st degree atrioventricular block or a complex bundle branch block
    6.Renal impairment: plasma creatinine >120 µmol/L
    7.Liver function tests (alkaline phosphatase, AST, ALT and/or γ-GT) above 2x the upper limit of normal
    1. Onbereidheid om zich te onthouden van alle medicatie, recrationeel drugs gebruik, en gebruik van anti-oxidant vitamene supplementen gedurdende het beloop van de studie en 7 dagen voor aanvang van de eerste studie dag.
    2. Onbereidheid om zich te onthouden van caffeine, nictoine of alcohol geduren
    3. Voorgaande deelname als proefpersoon in een trial waarbij LPS werd toegediend
    4. operatie of trauma met significant bloedverlies of bloed donatie 3 maanden voor aanvang van de studie
    5. Medische voorgeschiedenis, tekenen of symptomen van cardiovasculaire ziekte, met name:
    -verleden met frequente vaso-vagale collapsen of van orthostatische hypotensie.
    -een pols van ≤45 or ≥100 slagen/minuuut in rust.
    -hypertensie (RR systolisch >160 of RR diastolisch >90)
    -hypotensie RR systolisch <100 of RR diastolisch <50)
    -geleidingsstoornissen op het ECG bestaande uit een 1ste graads AV-blcok of een complex bundeltakblok
    6. Nierfunctie stoornissen: plasma creatinine>120 µmol/L
    7. Leverfunctie waardes (alkaline phosphatase, AST, ALT en/of γ-GT) meer dan 2x boven de bovengrens van de normaal waarde
    E.5 End points
    E.5.1Primary end point(s)
    Part 1: Safety and tolerability of EA-230

    Part 2: Modulation by EA-230 of the LPS-induced inflammatory response, quantified by the change in area under the curve (AUC) of the concentration * time curve of TNF-α during endotoxemia
    Deel 1: veiligheid en tolerantie van EA-230

    Deel 2: Modulatie van EA-230 op de LPS-geinduceerde acute systemische onstekingsreactie. Gedefinieerd als de verandering van de oppervalkte onder de curve en de concentratie*tijd curve van TNF-a
    E.5.1.1Timepoint(s) of evaluation of this end point
    5 timepoints: Day1 (testday), Day2, Day3, Day8, Day15
    5 tijdstippen: Dag1 (testdag), Dag2, Dag3, Dag8, Dag15
    E.5.2Secondary end point(s)
    Part 1:
    Pharmacokinetics of EA-230
    -Blood plasma levels of EA-230 and, if possible, metabolites, AUC, Cmax, terminal t1/2, Cl, V
    -Urinary excretion profile of EA-230 and, if possible, metabolites.
    Vital signs
    -blood pressure
    -heart rate
    Adverse events
    Safety parameters
    -Local tolerability at the site of i.v. infusion
    -Safety laboratory parameters (Hb, Ht, Leucocytes, thrombocytes, Leucocyte differential blood count, sodium, potassium, creatinine, urea, alkaline phosphatase, ALT, AST, γGT, CK, CRP)
    -Electrocardiogram (ECG), at baseline, just after IMP administration, and at 7 to 8 hrs after IMP administration

    Part 2:
    Modulation by EA-230 of the LPS-induced inflammatory response, quantified by the change in AUC of the concentration * time curve of other cytokines during endotoxemia (IL-6 and IL-10)
    Modulation by EA-230 of the LPS-induced leucocyte response, quantified by total WBC counts, neutrophil counts and monocyte counts over 24 hours after LPS challenge
    Modulation by EA-230 of markers of inflammation-induced kidney injury
    -Urinary excretion of NGAL, KIM-1, cystatin C, microalbumin, creatinine and urea
    -Plasma concentration of creatinine, urea, and NGAL in plasma
    Modulation by EA-230 of inflammation-induced changes in renal function
    -Glomerular filtration rate (GFR) measured by the clearance of iohexol
    Pharmacokinetics of EA-230
    -Blood plasma levels of EA-230 and, if possible, metabolites, AUC, Cmax, terminal t1/2, Cl, V
    -Urinary excretion profile of EA-230 and, if possible, metabolites.
    Vital signs
    -blood pressure
    -heart rate
    Adverse events
    Safety parameters
    -Local tolerability at the site of i.v. infusion
    -Safety laboratory parameters (Hb, Ht, Leucocytes, thrombocytes, Leucocyte differential blood count, sodium, potassium, creatinine, urea, alkaline phosphatase, ALT, AST, γGT, CK, CRP)
    -Electrocardiogram (ECG), at baseline, just after IMP administration, and at 7 to 8 hrs after IMP administration
    Deel 1:
    Pharmacokinetiek van EA-230
    -Bloed plasma spiegels en indien mogelijk van de metabolieten, AUC, Cmax, terminale t1/2, Cl, V.
    -Urine excretie profiel van EA-230 en indien mogelijk van de metabolieten.
    Vitale parameters
    -bloed druk
    -hart frequentie
    Bijwerkingen
    Veiligheidsparameters
    -lokale tolerantie bij de intraveneuze infusieplaats.
    -Lab waarden: Hb, Ht, Leukocyten, trombocyten, Leukocyten differenitatie, natrium, kaliium, creatinine, ureum, AF, ALAT, ASAT, gGT, CK, CRP.
    -Hartfilmpje (ECG), bij begin, na IMP toediening en 7 tot 8 uur na IMP toediening

    Deel 2:
    Modulatie van EA-230 op de LPS-geinduceerde acute systemische onstekingsreactie. Gedefinieerd als de verandering van de oppervlakte onder de curve en de concentratie*tijd curve van andere cytokines (IL-6 en IL-10)
    Modulatie van EA-230 op de LPS-geinduceerde leucocyten reactie. Gedefinieerd als het totaal aantal witte bloedcellen, totaal aantal neutrofielen en totaal aantal monocyten.
    Modulatie van EA-230 op markers van onsteking-geinduceerde nierschade.
    -Urine excretie van NGAL, KIM-1, cystatin C, micralbumine, creatinine en ureum
    -Plasma concentratie van creatinine, ureum en NGAL in plasma
    Modulatie van EA-230 op de nierfunctie
    -GFR gemeten door de klaring van iohexol
    Pharmacokinetiek van EA-230
    -Bloed plasma spiegels van EA-230 en indien mogelijk van de metabolieten, AUC, Cmax, terminale t1/2, Cl, V.
    -Urine excretie profiel van EA-230 en indien mogelijk van de metabolieten.
    Vitale parameters
    -bloed druk,
    -hart frequentie
    Bijwerkingen
    Veiligheids parameters
    -lokale tolerantie bij de intraveneuze infusieplaats.
    -Lab waarden: Hb, Ht, Leukocyten, trombocyten, Leukocyten differenitatie, natrium, kaliium, creatinine, ureum, AF, ALAT, ASAT, gGT, CK, CRP.
    -Hartfilmpje (ECG), bij begin, na IMP toediening en 7 tot 8 uur na IMP toediening
    E.5.2.1Timepoint(s) of evaluation of this end point
    6 timepoints: Day-1, Day1(testday), Day2, Day3, Day8, Day15
    6 tijdstippen: Dag-1, Dag1(testdag), Dag2, Dag3, Dag8, Dag15
    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 No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    An earlier first administration to humans has been performed before
    een eerste toediening bij mensen is al eerder gedaan
    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 trial4
    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.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned 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: 60
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female No
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    F.3.2Patients No
    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 state60
    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
    geen
    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 Decision2014-09-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-10-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-06-26
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