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    Summary
    EudraCT Number:2011-004311-23
    Sponsor's Protocol Code Number:HOTstudy_Thomas11
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-11-01
    Trial results Removed from public view
    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 ConcernedUK - MHRA
    A.2EudraCT number2011-004311-23
    A.3Full title of the trial
    A randomised, placebo controlled trial to study the effect of heme-arginate on heme-oxygenase-1 induction and renal function in recipients of deceased donor renal transplants.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to see whether giving the drug heme-arginate to recipients before kidney transplant can increase the level of a protective protein and protect their transplanted kidney.
    A.3.2Name or abbreviated title of the trial where available
    Heme-oxygenase-1 in renal transplantation (HOT study)v.1
    A.4.1Sponsor's protocol code numberHOTstudy_Thomas11
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01430156
    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 SponsorUniversity of Edinburgh
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNHS Blood and Transplant
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationACCORD
    B.5.2Functional name of contact pointDr Lynn Morrice
    B.5.3 Address:
    B.5.3.1Street Address47 Little France Crescent
    B.5.3.2Town/ cityEdinburgh
    B.5.3.3Post codeEH17 8TN
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01312423325
    B.5.5Fax number01312429447
    B.5.6E-maillynn.morrice@ed.ac.uk
    B.Sponsor: 2
    B.1.1Name of SponsorNHS Lothian
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    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 organisationNHS Lothian
    B.5.2Functional name of contact pointKaren Maitland
    B.5.3 Address:
    B.5.3.1Street AddressQMRI, 47 Little France Crescent
    B.5.3.2Town/ cityEdinburgh
    B.5.3.3Post codeEH16 4TJ
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01312423328
    B.5.5Fax number01312423343
    B.5.6E-mailkaren.maitland@luht.scot.nhs.uk
    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 Normosang
    D.2.1.1.2Name of the Marketing Authorisation holderOrphan Europe
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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.3.4Pharmaceutical form Concentrate for 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 INNhuman hemin
    D.3.9.1CAS number 16009-13-5
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number21.2 to 26.2
    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) 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 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.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
    Ischaemia-reperfusion injury in renal transplantation
    E.1.1.1Medical condition in easily understood language
    The inevitable kidney damage that happens after transplant due to interruption in blood flow.
    E.1.1.2Therapeutic area Body processes [G] - Cell Physiological Phenomena [G04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10014646
    E.1.2Term End stage renal disease (ESRD)
    E.1.2System Organ Class 100000004857
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10023438
    E.1.2Term Kidney transplant
    E.1.2System Organ Class 100000004865
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Does treating the recipients of deceased donor kidneys with heme-arginate (HA) increase the amount of HO-1 protein in the recipient’s white blood cells compared to placebo treatment?
    E.2.2Secondary objectives of the trial
    Does treating the recipients of deceased donor kidneys with heme-arginate (HA) increase the amount of HO-1 mRNA in the recipient’s white blood cells compared to placebo treatment at 24 hours?

    How does the recipient's white blood cell HO-1 mRNA and protein expression change over the 5 days after HA/placebo injection?

    Does treating the recipients of deceased donor kidneys with heme-arginate (HA) increase HO-1 protein expression in the transplanted kidney at day 5 compared to placebo treatment?

    Does HA improve outcome after transplantation by preventing delayed graft function compared to placebo?

    Does HA treatment reduce histological injury in the transplanted kidney compared to placebo treatment?

    Can we predict the amount of injury a transplanted kidney has sustained by measuring biological markers in the urine?
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    All patients receiving a single kidney deceased donor transplant.
    All patients receiving standard immunosuppression.
    E.4Principal exclusion criteria
    Patients unable to receive the standard immunosuppressive regimen
    Patients unable to give informed consent
    Patients with known hypersensitivity reactions to HA
    Patients receiving more than one organ
    Patients receiving their 3rd or subsequent kidney transplant
    Patients who are fully anticoagulated pre-operatively
    Patients on combined anti-platelet agents
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome measure is the difference in HO-1 protein expression in the recipient monocyte/macrophages between pre-infusion and 24 hours post-infusion levels as measured by Western Blot comparing Heme-arginate (HA) with placebo.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Blood test at 24 hours after HA infusion. We are allowing an eight hour window (20-28 hours post-infusion)for this blood test.
    E.5.2Secondary end point(s)
    The difference in levels of HO-1 mRNA as measured by PCR in the recipient monocytes/macrophages between the pre-infusion sample and the 24 hours post-infusion samples comparing HA vs. placebo.

    The difference in levels of HO-1 expression in the transplanted kidney as determined by immunohistochemical analysis between the pre-operative biopsy sample and the day 5 biopsy sample in participants who have received HA vs. those that have received placebo.

    The difference in histological injury in the transplanted kidney as determined by the Pathologist between the pre-operative sample and the day 5 sample comparing HA to placebo.

    The difference in incidence of delayed graft function in participants who received HA compared to placebo.

    We will determine whether the level of urinary biomarkers in post-transplant urine samples by ELISA has a relationship with with poor renal function in transplant recipients as determined by the incidence of delayed graft function.

    The pattern of the change in recipient's white blood cell HO-1 mRNA and protein expression over the 5 days of the study for both HA treatment group and placebo treatment group.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The HO-1 mRNA induction in monocytes is measured at 24 hours post infusion (blood sample window of 20-28 hours).

    HO-1 induction in renal tissue and histological renal injury is measured at 5 days post transplant.

    Delayed graft function is assessed from the results of daily routine blood tests from day 1 to day 7 post transplant.

    Urinary biomarkers will be measured daily from day 1-5 when the participant starts producing urine.

    The pattern of the monocyte HO-1 expression will be evaluated from samples taken pre-operatively and on days 1-5 post-op.
    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 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) 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 Yes
    E.8.1.4Double blind No
    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.8.2.4Number of treatment arms in the trial2
    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 Information not present in EudraCT
    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
    United Kingdom
    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 end of the trial is defined as the discharge of the last patient from hospital or day 7 of their in-patient stay, which ever is earlier.
    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 months5
    E.8.9.1In the Member State concerned days28
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days28
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    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: 35
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 5
    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 state40
    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)
    There is no need for continued provision of the intervention for the research participants beyond the end of the trial. However, all transplant patients are followed up for life at the transplant clinic.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation N/A
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2011-11-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-09-30
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-08-27
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