Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2021-001245-13
    Sponsor's Protocol Code Number:4LB-LEO-P
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2022-01-19
    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 number2021-001245-13
    A.3Full title of the trial
    A randomized, double-blind, placebo-controlled, two parallel groups, international multicenter trial to evaluate the effect of Plerixafor in acute respiratory failure related to COVID-19 (LEONARDO)
    Een gerandomiseerd, dubbelblind, placebogecontroleerd, internationaal multicenteronderzoek met twee parallelle groepen om de effectiviteit te beoordelen van Plerixafor bij acuut ademhalingsfalen door COVID-19 (LEONARDO)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Plerixafor in acute respiratory distress syndrome related to covid-19 (Phase IIb)
    Plerixafor bij acuut ademhalingsfalen door COVID-19 (fase IIb)
    A.3.2Name or abbreviated title of the trial where available
    LEONARDO
    A.4.1Sponsor's protocol code number4LB-LEO-P
    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 Sponsor4Living Biotech SAS
    B.1.3.4CountryFrance
    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 support4 Living Biotech
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation4Living Biotech SAS
    B.5.2Functional name of contact pointClinical trial information
    B.5.3 Address:
    B.5.3.1Street AddressCampus de l’Institut Pasteur de Lille, 1 rue du Professeur Calmette
    B.5.3.2Town/ cityLille
    B.5.3.3Post code59000
    B.5.3.4CountryFrance
    B.5.6E-mail4LB-Leonardo@labcorp.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 Yes
    D.2.1.1.1Trade name Mozobil 20 mg/ml solution for injection
    D.2.1.1.2Name of the Marketing Authorisation holderGenzyme Corporation
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 Solution for injection
    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 INNPlerixafor
    D.3.9.1CAS number 110078-46-1
    D.3.9.4EV Substance CodeSUB28849
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 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
    Severe COVID-19
    ernstige COVID-19
    E.1.1.1Medical condition in easily understood language
    Severe COVID-19
    ernstige COVID-19
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level PT
    E.1.2Classification code 10084268
    E.1.2Term COVID-19
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.1
    E.1.2Level PT
    E.1.2Classification code 10084380
    E.1.2Term COVID-19 pneumonia
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate that Plerixafor is able to reduce the need for invasive mechanical ventilation or death in severe COVID-19 patients admitted in Intensive Care Unit (ICU)
    Aantonen dat plerixafor de noodzaak voor invasieve mechanische beademing of sterfte bij patiënten met ernstige COVID-19 die zijn opgenomen op de Intensive Care Unit (ICU) kan verkleinen
    E.2.2Secondary objectives of the trial
    To evaluate the efficacy of Plerixafor compared to placebo on
    • Mortality between randomization and D28
    • Mortality between randomization and D90
    • Ventilator-free days between randomization and D28
    • Duration of mechanical ventilation between randomization and D90
    • Length of ICU stay between randomization and D90
    • Respiratory function including Forced Expiratory Volume in one sec (FEV1), Forced Vital Capacity (FVC), arterial partial pressure of oxygen (PaO2) and Transfer Lung Capacity for carbon monoxide (TLCO), 6-minute walk test [Time Frame: D90]
    • Clinical improvement [Time Frame: D1, D8, D14, D28, D90]
    • Level of consciousness [Time Frame: D1-D8, D14, D28, D90]
    • Respiratory/oxygenation status [Time Frame: D1-D8, D14, D28, D90]
    CRP, fibrinogen and D-dimers levels [Time Frame: D1, D3, D8, D14, D28]
    To evaluate the safety and tolerability of Plerixafor compared to placebo on
    • Safety (AEs, vital signs, lab tests)
    De werkzaamheid van plerixafor beoordelen in vergelijking met placebo ten aanzien van
    •Sterfte tussen randomisatie en D28
    •Sterfte tussen randomisatie en D90
    •Beademingsvrije dagen tussen randomisatie en D28
    •Duur van mechanische beademing tussen randomisatie en D90
    •Duur verblijf ICU tussen randomisatie en D90
    •Respiratoire functie waaronder geforceerd expiratoir volume in één seconde (FEV1), geforceerde vitale capaciteit (FVC), partiële zuurstofspanning in arterieel bloed (PaO2) en diffusiecapaciteit van de long voor koolmonoxide (TLCO), 6-minuten-wandeltest
    •Klinische verbetering
    •Mate van bewustzijn
    •Status ademhaling/zuurstoftoevoer
    Gehalte CRP, fibrinogeen en D-dimeren
    Het beoordelen van de veiligheid en verdraagbaarheid van plerixafor in vergelijking met placebo ten aanzien van
    •Veiligheid (bijwerkingen, vitale functies, labtesten)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • I1 Male or female ≥ 18 years of age,
    • I2 Using contraceptive consistent with local regulations regarding the methods of contraception for those participating in clinical studies,
    • I3 Willing and able to provide written informed consent (or provided by legally acceptable representative if he/she is present and if in line with local regulations),
    • I4 Admitted in ICU within 48 hours before randomization for COVID-19 related respiratory failure.
    ◦ ICU or equivalent medical structure according to country specificities e.g., Acute Respiratory Care Unit, High Dependency Care Unit if they can provide:
    ▪ continuous IV infusion,
    ▪ continuous ECG, respiratory rate, percutaneous oxygen saturation screen monitoring
    ▪ high flow nasal oxygen
    • I5 Not requiring immediate (within 24-36 hours) invasive mechanical ventilation according to investigator's judgment,
    • I6 Confirmed pneumoniae due to SARS-CoV-2 with Laboratoryconfirmed SARS-CoV-2 infection as determined by RT-PCR (in nasopharynx or throat samples) or other commercial or public health assay in any specimen, performed within 2 weeks prior to randomization,
    • I7 Acute respiratory failure requiring oxygen support (≥ 5L/min) to achieve a transcutaneous oxygen saturation > 94%,
    • I8 Estimated glomerular filtration rate (eGFR) > 50 mL/min/1.73m² by the CKD-EPI (Chronic Kidney Disease – Epidemiology Collaboration) equation.

    Patients vaccinated against SARS-CoV-2 can be included in the study.
    During the whole study, patients will receive standard of care for ethical reasons (e.g. glucocorticoids)
    E.4Principal exclusion criteria
    • E1 Pregnancy or breast feeding,
    • E2 Anticipated transfer to another hospital, which is not a study site within 72 hours of randomisation,
    • E3 Need for Invasive mechanical ventilation at time of inclusion,
    • E4 Evidence of uncontrolled bacterial pneumopathy or active infection other than SARS-Cov-2 (laboratory confirmation),
    • E5 Primitive pulmonary arterial hypertension,
    • E6 Cardio-vascular co-morbidity:
    o History of vascular ischemic events (myocardial infarction or stroke) or congestive heart failure or peripheral arterial disease,
    o History or current significant cardiac rhythm disorders (e.g., ventricular tachycardia),
    o Known medical history of proven symptomatic postural hypotension,
    • E7 Evolutive cancer including acute and chronic leukaemia,
    • E8 Inadequate haematological function defined by:
    o Neutrophil count < 1.0 x 109/L,
    o Haemoglobin < 9.0 g/dL (90 g/L),
    o Platelets < 100 x 109/L,
    • E9 Kaliemia < 3.5 mmol/L and/or total Calcemia < 2.2 mmol/L,
    • E10 Inadequate hepatic function defined by Aspartate aminotransferase (AST) and/or Alanine Aminotransferase (ALT) > 3 x upper limit of normal (ULN) and/or Total bilirubin > 2 x ULN,
    • E11 Patients with known allergy to Plerixafor or its excipients.
    • E12 Previous (within 4 weeks) or current participation in another clinical study other than an observational study.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of patients with need for invasive mechanical ventilation or death between randomization and D28
    Deel van de patiënten dat invasieve mechanische beademing nodig heeft of overlijdt tussen randomisatie en D28
    E.5.1.1Timepoint(s) of evaluation of this end point
    From D1 to D28
    dag 1–dag 28
    E.5.2Secondary end point(s)
    • Percentage of death (all-cause mortality)
    • Number of Ventilator-free days
    • Duration of invasive mechanical ventilation in survivors
    • Number of ICU stay days
    • Respiratory function at 3 months (FEV-1, FVC, PaO2, TLCO, 6-minute walk test)
    • Ordinal Scale for Clinical Improvement (7 point-WHO scale)
    • Level of consciousness (Alert, Voice, Pain, Unresponsive scale)
    • SpO2 measured via pulse oxymetry and arterial blood gas: Partial pressure of oxygen (PaO2), Partial pressure of carbon dioxide (PaCO2), Bicarbonate (HCO3), Oxygen saturation (O2 Sat), pH, Base excess (when performed before intubation)
    • Blood CRP, fibrinogen, D-dimers levels
    • Incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs),
    • Incidence of Plerixafor discontinua-tion and withdrawals due to TEAEs
    • WBC count and differential, RBC count, hemoglobin level, MCV, Reticulocyte and Platelet counts
    • Blood Chemistry (Creatinine, AST, ALT, total bilirubin, K, total Ca)
    •Percentage overlijdens (sterfte door alle oorzaken)
    •Aantal beademingsvrije dagen
    •Duur invasieve mechanische beademing bij overlevers
    •Aantal dagen verblijf ICU
    •Respiratoire functie na 3 maanden (FEV-1, FVC, PaO2, TLCO, 6-minuten-wandeltest)
    •Ordinale schaal voor klinische verbetering (7-punts WHO-schaal)
    •Mate van bewustzijn (schaal voor alertheid, reactie op spraak, reactie op pijn, geen reactie)
    •SpO2 gemeten met pulsoxymetrie en arterieel bloedgas: partiële zuurstofspanning (PaO2), partiële kooldioxidespanning (PaCO2), bicarbonaat (HCO3), zuurstofsaturatie (O2 Sat), pH, basenoverschot (indien uitgevoerd vóór intubatie)
    •Concentratie CRP, fibrinogeen, D-dimeren in bloed
    •Incidentie van TEAE's (‘treatment-emergent AE's’, bijwerkingen die tijdens de behandeling optreden), SAE's (‘serious AE's’, ernstige bijwerkingen) en AESI's (‘AE's of special interest’, bijzondere bijwerkingen)
    •Incidentie van tijdelijk of permanent staken van gebruik plerixafor vanwege TEAE's
    •Telling en differentiatie witte bloedcellen, telling rode bloedcellen, hemoglobineconcentratie, MCV (‘Mean Corpuscular Volume’, gemiddelde volume rode bloedcellen), telling reticulocyten en bloedplaatjes
    •Bloedchemie (creatinine, ASAT, ALAT, totaal bilirubine, K, totaal Ca)
    E.5.2.1Timepoint(s) of evaluation of this end point
    • Death:D1-28 and D1-90
    • Nb of Ventilator-free days:D1-D28
    • Duration of invasive mechanical ventilation in survivors:D1-D90
    • ICU stay days:D1-D90
    • Respiratory function: D90
    • Ordinal Scale for Clinical Improvement:D1, D8, D14 D28, D90
    • Level of consciousness:D1-D8, D14, D28, D90
    • SpO2 and arterial blood gas: D1-D8, D14, D28, D90
    • Blood CRP, fibrinogen, D-dimers levels:D1, D3, D8, D14, D28
    • TEAEs, SAEs, AESIs, Incidence of Plerixafor discontinuation and withdrawals due to TEAEs: Continuous up to D90 (or at time of AE recovery if persistent at D90)
    • WBC count and differential, RBC count, hemoglobin level, MCV, Reticulocyte and Platelet counts and blood chemistry:D1, D3, D5, D8, D14, D28
    Percentage overlijdens: D1–28 en D1-90
    Aantal beademingsvrije dagen: D1–28
    Duur invasieve mechanische beademing bij overlevers: D1–90
    Aantal dagen verblijf ICU: D1–90
    Respiratoire functie : D90
    Ordinale schaal voor klinische verbetering: D1, D8, D14, D28, D90
    Mate van bewustzijn: D1–8, D14, D28, D90
    SpO2 en arterieel bloedgas: D1–8, D14, D28, D90
    Concentratie CRP, fibrinogeen, D-dimeren in bloed: D1, D3, D8, D14, D28
    Incidentie van TEAE's, SAE's, AESI's en van tijdelijk of permanent staken van gebruik IMP vanwege TEAE's: aanhoudend t/m D90 (of ten tijde van herstel van AE, indien nog aanwezig op D90)
    Telling en differentiatie witte bloedcellen, telling rode bloedcellen, hemoglobineconcentratie, MCV, telling reticulocyten en bloedplaatjes en Bloedchemie: D1, D3, D5, D8, D14, D28
    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 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 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 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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    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
    Bulgaria
    France
    Netherlands
    Spain
    Ukraine
    United States
    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
    LVLS
    Laatste bezoek, laatste patiënt
    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 months7
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months7
    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: 90
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 60
    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 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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 150
    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)
    Standard of care as per Investigator's decision
    Zorgstandaard volgens de beslissing van de onderzoeker
    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 Decision2022-01-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-07-28
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2022-10-01
    For support, Contact us.
    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
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 05 15:32:12 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA