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    Summary
    EudraCT Number:2017-000584-33
    Sponsor's Protocol Code Number:16154DMcA-AS
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2017-11-28
    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 ConcernedUK - MHRA
    A.2EudraCT number2017-000584-33
    A.3Full title of the trial
    Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST) trial: An open label dose escalation phase 1 trial followed by a randomised, double-blind, placebo-controlled phase 2 trial.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Mesenchymal stromal cells as a new treatment for a disease called ARDS
    A.3.2Name or abbreviated title of the trial where available
    Repair of ARDS by Stromal Cell Administration (REALIST)
    A.4.1Sponsor's protocol code number16154DMcA-AS
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03042143
    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 SponsorBelfast Health and Social Care Trust
    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 supportThe Wellcome Trust
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationQueen's University Belfast
    B.5.2Functional name of contact pointDanny McAuley
    B.5.3 Address:
    B.5.3.1Street AddressWelcome-Wolfson Building, 97 LIsburn Road
    B.5.3.2Town/ cityBelfast
    B.5.3.3Post codeBT9 7AE
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02890976385
    B.5.6E-maild.f.mcauley@qub.ac.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 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 nameREALIST ORBCEL-C
    D.3.2Product code N/A
    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 INNOrbcel-C
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number100 million cells to 400 million cells
    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) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    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
    Acute Respiratory Distress Syndrome
    E.1.1.1Medical condition in easily understood language
    In patients mechanically ventilated in ICU, for reasons that are unclear, their lungs fail and fill with water making breathing difficult. This is termed Acute Respiratory Distress Syndrome (ARDS)
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    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
    The principal research question is to determine whether in adult patients with moderate to severe ARDS, human umbilical cord derived CD362 enriched MSCs, (REALIST ORBCEL-C cells) are safe and improve important surrogate clinical outcomes.

    The primary objective is to assess the safety of a single intravenous infusion of REALIST ORBCEL-C cells in patients with ARDS.
    E.2.2Secondary objectives of the trial
    The secondary objective is to determine the effect of a single intravenous infusion of REALIST ORBCEL-C cells on:

    1. Physiological indices of respiratory dysfunction reflecting severity of ARDS, as measured by oxygenation index (OI), respiratory compliance, and P/F ratio.
    2. Sequential organ failure assessment (SOFA) score.
    3. Alveolar and systemic markers of inflammatory responses.
    4. Alveolar and systemic markers of cell specific injury.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Moderate to severe ARDS as defined by the Berlin definition
    a)Onset within 1 week of identified insult
    b)Within the same 24-hour time period
    i. Hypoxic respiratory failure (PaO2/ FiO2 ratio less than or equal to 27kPa on PEEP more than or equal to 5cmH2O)
    ii.Bilateral infiltrates on chest x-ray consistent with pulmonary oedema not explained by another pulmonary pathology
    iii.Respiratory failure not fully explained by cardiac failure or fluid overload
    2. Patient is receiving invasive mechanical ventilation
    E.4Principal exclusion criteria
    1. More than 48 hours from the onset of ARDS
    2. Age <16 years
    3. Patient is known to be pregnant
    4. Participation in a clinical trial of an investigational medicinal product
    within 30 days
    5. Major trauma in the prior 5 days
    6. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last year
    7. WHO Class III or IV pulmonary hypertension
    8. Venous thromboembolism currently receiving anti-coagulation or within the last 3 months.
    9. Currently receiving extracorporeal life support (ECLS)
    10. Severe chronic liver disease with Child-Pugh score >12
    11. DNAR (Do Not Attempt Resuscitation) order in place
    12. Treatment withdrawal imminent within 24 hours
    13. Consent declined
    14. Prisoners
    15. Non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available
    16. Previously enrolled in the REALIST trial
    E.5 End points
    E.5.1Primary end point(s)
    Primary safety outcome: The safety and tolerability of MSCs as defined by the incidence of serious adverse events (SAEs)

    Primary efficacy outcome: Oxygenation index (OI) at day 7
    E.5.1.1Timepoint(s) of evaluation of this end point
    We have chosen day 7 as we expect this time interval will minimise the competing effects of death and extubation while allowing a sufficient time interval for a biological effect to occur.
    E.5.2Secondary end point(s)
    1) Oxygenation Index (OI) at days 4 and 14
    2) Respiratory compliance and P/F ratio at days 4,7 and 14
    3) Sequential Organ Failure Assessment (SOFA) score at days 4,7 and 14
    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) Yes
    E.7.1.1First administration to humans Yes
    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 Yes
    E.8.1.7.1Other trial design description
    Phase 1: Dose escalation, Phase 2:Randomised, double-blind, controlled
    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 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 concerned5
    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 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 study will end when all phase 1 and phase 2 patients have completed 2 year follow up and database lock occurs.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days31
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months0
    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: 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) Yes
    F.1.1.6.1Number of subjects for this age range: 4
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 70
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 4
    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 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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Critically ill patients in intensive care units are sedated and critically ill without capacity to give consent
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state78
    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 plan for continued provision of REALIST ORBCEL-C for the trial participants. At the end of the study, patients will continue on their standard care pathway.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-02-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-02-06
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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