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:2018-003144-23
    Sponsor's Protocol Code Number:2017/81
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-08-09
    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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2018-003144-23
    A.3Full title of the trial
    Treating severe brain-injured patients with apomorphine : a behavioural and neuroimaging study
    Traitement des patients cérébro-lésés avec l'apomorphine : une étude pilote comportementale et en neuroimagerie
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Treating severe brain-injured patients with apomorphine
    Traitement des patients cérébro-lésés avec l'apomorphine
    A.4.1Sponsor's protocol code number2017/81
    A.5.4Other Identifiers
    Name:Belgian national numberNumber:B707201731937
    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 Liège
    B.1.3.4CountryBelgium
    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 supportNeuroHealing Pharmaceuticals Inc.
    B.4.2CountryUnited States
    B.4.1Name of organisation providing supportBritannia Pharmaceuticals Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity of Liège
    B.5.2Functional name of contact pointComa Science Group
    B.5.3 Address:
    B.5.3.1Street AddressCHU de Liège, B34, Avenue de l'Hopital, 1
    B.5.3.2Town/ cityLiège
    B.5.3.3Post code4000
    B.5.3.4CountryBelgium
    B.5.4Telephone number003243663915
    B.5.6E-mailcoma@uliege.be
    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 APO-go® PFS 5 mg/ml Solution for Infusion in Pre-filled Syringe
    D.2.1.1.2Name of the Marketing Authorisation holderBritannia Pharmaceuticals Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationBelgium
    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 infusion in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApomorphine Hydrochloride
    D.3.9.1CAS number 314-19-2
    D.3.9.3Other descriptive nameANHYDROUS APOMORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB127079
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 infusion in pre-filled syringe
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Disorders of consciousness
    Troubles de l'état de conscience
    E.1.1.1Medical condition in easily understood language
    Disorders of consciousness
    Troubles de la conscience
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    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
    This clinical trial aims to clarify the prevalence of responders and the efficacy of apomorphine hydrochloride subcutaneous infusions for the treatment of patients with disorders of consciousness.
    Cet essai clinique vise à clarifier la prévalence des répondeurs et l'efficacité du chlorhydrate d'apomorphine par infusions sous-cutanées pour le traitement des patients présentant des troubles de la conscience.
    E.2.2Secondary objectives of the trial
    This study aims to also better characterize the phenotype of potential good candidates to apomorphine treatment and identify a set of biomarkers that correlate with responsiveness (or non-responsiveness) to the therapy, as well as help underpin the neural networks underlying the modulating action of apomorphine on consciousness.
    Cette étude vise également à mieux caractériser le phénotype des candidats potentiels répondeurs au traitement par apomorphine et à identifier les biomarqueurs en corrélation avec le degré de réponse au traitement, ainsi qu'à mettre en évidence les réseaux neuronaux sous-jacents à l'action modulatrice de l'apomorphine sur la conscience.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    "Treating severe brain-injured patients with apomorphine: a behavioral and neuroimaging pilot study", protocol version 2, dated 03/08/2018

    This preliminary open-label pilot study on 6 patients with disorders of consciousness is designed to evaluate the feasibility of the subsequent randomized clinical trial, as well as provide initial data on responsiveness rates to apomorphine treatment, phenotype of responders and effect size.
    "Traitement des patients cérébro-lésés avec l'apomorphine : une étude pilote comportementale et en neuroimagerie", protocole version 2 daté du 03/08/2018

    Cette étude pilote préliminaire en open-label sur 6 patients présentant des troubles de la conscience vise à évaluer la faisabilité de l'essai clinique randomisé ultérieur et fournir des données initiales sur les taux de répondeurs au traitement par apomorphine, le phénotype des répondeurs et l'intensité de l'effet observé.
    E.3Principal inclusion criteria
    - 18-55 years old.
    - Clinically stable, not dependent on medical ventilators for respiration.
    - Diagnosed as in an unresponsive wakefulness syndrome or minimally conscious state according to the international criteria and based on at least 2 consistent CRS-R in the last 14 days (one CRS-R in the last 7 days).
    - More than 6 weeks post-insult
    - Informed consent from patient or legal representative of the patient.
    - Patient âgé de 18 à 55 ans.
    - Cliniquement stable, ne dépendant pas des ventilateurs médicaux pour la respiration.
    - Diagnostic de syndrome d'éveil non-répondant ou d'état de conscience minimale selon les critères internationaux et basé sur au moins 2 CRS-R concordantes au cours des 14 derniers jours (une CRS-R au cours des 7 derniers jours).
    - Plus de 6 semaines depuis la lésion cérébrale
    - Consentement éclairé du patient ou du représentant légal du patient.
    E.4Principal exclusion criteria
    - Use of dopamine agonists or antagonists (e.g. amantadine, bromocriptine, l-dopa, pramipexole, ropinirole, amphetamine, bupropion, methylphenidate / risperidone, haloperidol, chlorpromazine, flupentixol, clozapine, olanzapine, quetiapine) in the last 2 weeks or 4 half-lives of the drug.
    - Use of neurological medications other than anti-epileptic or anti-spasticity drugs in the last 2 weeks or 4 half-lives of the drug.
    - Use of drugs with known significant prolongation of the QT interval (e.g. class 1 antiarrythmics, sotalol, macrolides, quinolones, antipsychotic drugs, tricyclic antidepressants, methadone, chloroquine, quinine) in the last 2 weeks or 4 half-lives of the drug.
    - A corrected QT interval over 480ms (calculated using Bazett’s formula on a standard 12-lead ECG recorded in the last 14 days) or other risk factors for arrhythmia (congestive cardiac failure, severe hepatic impairment or significant electrolyte disturbance).
    - A history of previous neurological functional impairment other than related to their acquired brain injury.
    - Contraindication to MRI, EEG, or PET (e.g., electronic implanted devices, active epilepsy, external ventricular drain).
    - Use of nitrates or other vasodilators, central nervous system acting agents such as barbiturates, morphine and related drugs (relative exclusion criterion)
    - Utilisation d'agonistes ou d'antagonistes de la dopamine (par exemple amantadine, bromocriptine, L-dopa, pramipexole, ropinirole, amphétamines, bupropion, méthylphénidate / risperidone, halopéridol, chlorpromazine, flupentixol, clozapine, olanzapine, quétiapine) au cours des 2 dernières semaines ou quatre demi-vies du médicament.
    - Utilisation de médicaments à action neurologique autres que les médicaments antiépileptiques ou antispastiques au cours des 2 dernières semaines ou 4 demi-vies du médicament.
    - Utilisation de médicaments provoquant prolongation documentée de l'intervalle QT (par exemple antiarythmiques de classe 1, sotalol, macrolides, quinolones, antipsychotiques, antidépresseurs tricycliques, méthadone, chloroquine, quinine) au cours des 2 dernières semaines ou 4 demi-vie du médicament.
    - Un intervalle QT corrigé supérieur à 480ms (calculé en utilisant la formule de Bazett sur un ECG standard à 12 dérivations enregistré dans les 14 derniers jours) ou d'autres facteurs de risque d'arythmie (insuffisance cardiaque congestive, insuffisance hépatique grave ou perturbation électrolytique significative).
    - antécédents d'atteinte neurologique autre que la lésion cérébrale acquise.
    - Contre-indication à l'IRM, à l'EEG ou à la TEP (par exemple dispositifs implantés électroniques, épilepsie active, drain ventriculaire externe).
    - Utilisation de nitrates ou d’autres vasodilatateurs, d’agents agissant sur le système nerveux central tels que les barbituriques, morphiniques (critère d’exclusion relative)
    E.5 End points
    E.5.1Primary end point(s)
    Change of diagnosis from baseline in Coma Recovery Scale - Revised (CRS-R)
    Changement de diagnostic par rapport à la baseline en utilisant l'échelle de récupération du coma - Révisé (CRS-R)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Once a week from inclusion until day 90.
    Une fois par semaine depuisl'inclusion jusqu'au jour 90.
    E.5.2Secondary end point(s)
    1-Change of total score in Nociception Coma Scale - Revised (NCS-R)
    2-Changes in EEG spectral power within fixed bands or dynamic connectivity using median spectral connectivity and graph-theoretic topology metrics
    3-Changes in the probabilty of consciousness using a multivariate EEG classifier based on a machine-learning approach using 120 EEG markers.
    4-Changes in quantification of PET signal using standardized uptake values of fluorodeoxyglucose
    5-Changes in MRI functional connectivity using a seed-voxel approach, between regions of interest (here: striatum, globus pallidus interna, thalamus and prefrontal cortex) and the time course from all other brain voxels.
    6-Change in circadian rhythmicity using actimetry and body temperature variations
    7-Change in the architecture of sleep cycles using night EEG
    8-Change of score in Glasgow Outcome Scale - Extended (GOS-E)
    9-Change in diagnosis in Phone-adapted CRS-R
    1-Changement du score total dans la Nociception Coma Scale - Revised (NCS-R)
    2-Changement de la puissance spectrale de EEG dans des bandes fixes de fréquences ou de connectivité dynamique en utilisant la connectivité spectrale médiane et des mesures topologiques de la théorie des graphes.
    3-Changement de la probabilité de conscience donnée par un classificateur EEG multivarié basé sur une approche de machine-learning utilisant 120 marqueurs EEG.
    4-Changements dans la quantification du signal TEP en utilisant des valeurs d'absorption normalisées du fluorodésoxyglucose (SUV)
    5-Modifications de la connectivité fonctionnelle IRM en utilisant une approche seed-voxels, entre les régions d'intérêt (ici striatum, globus pallidus interna, thalamus et cortex préfrontal) et tous les autres voxels cérébraux.
    6-Changement de la rythmicité circadienne utilisant l'actimétrie et les variations de température du corps
    7-Changement de l'architecture des cycles de sommeil par EEG de nuit
    8-Changement de score à la Glasgow Outcome Scale - Extended (GOS-E)
    9-Changement de diagnostic à la CRS-R adaptée à l'entretien téléphonique
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-Once a week from inclusion until day 90.
    2-Once a week from inclusion until day 90.
    3-Once a week from inclusion until day 90.
    4- Before treatment (day 22) and after treatment (day 62)
    5- Before treatment (day 26) and after treatment (day 62)
    6- Continuously from inclusion until day 90
    7- Before treatment (day 29) and after treatment (day 63)
    8- 6 months, 12 months and 24 months after treatment
    9- 6 months, 12 months and 24 months after treatment
    1- Une fois par semaine de l'inclusion jusqu'au jour 90.
    2- Une fois par semaine de l'inclusion jusqu'au jour 90.
    3- Une fois par semaine de l'inclusion jusqu'au jour 90.
    4- Avant le traitement (jour 22) et après le traitement (jour 62)
    5- Avant le traitement (jour 26) et après le traitement (jour 62)
    6- En continu depuis l'inclusion jusqu'au jour 90
    7- Avant le traitement (jour 29) et après le traitement (jour 63)
    8- A 6 mois, 12 mois et 24 mois après le traitement
    9- A 6 mois, 12 mois et 24 mois après le traitement
    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 No
    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 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 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 concerned2
    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
    Last follow-up phone call of the last subject
    Dernier appel téléphonique de suivi du dernier sujet
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    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: 54
    F.1.3Elderly (>=65 years) No
    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 Information not present in EudraCT
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    F.3.3.3Pregnant women Information not present in EudraCT
    F.3.3.4Nursing women Information not present in EudraCT
    F.3.3.5Emergency situation Information not present in EudraCT
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Patients with disorders of consciousness, more specifically with an unresponsive wakefulness syndrome or in a minimally conscious state.
    Patients présentant des troubles de la conscience, plus précisément un syndrome d'éveil non-répondant ou un état de conscience minimale.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state54
    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)
    Possible extension of the apomorphine treatment after day 90 at the last prescribed dose, provided that the patient has shown a clinical improvement during treatment and a degradation at treatment withdrawal. This decision will be taken according to the referent physician's clinical judgment.
    Extension possible du traitement par apomorphine après le jour 90 en utilisant la dernière dose prescrite, à condition que le patient ait montré une amélioration clinique au cours du traitement et une dégradation lors de son arrêt. Cette décision sera prise selon le jugement clinique du médecin référent.
    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 Decision2018-09-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-05-16
    P. End of Trial
    P.End of Trial StatusOngoing
    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-Sat May 04 16:22:15 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA