E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
De Novo Parkinson’s disease |
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E.1.1.1 | Medical condition in easily understood language |
De Novo Parkinson’s disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of the FAIR-PARK II trial is to demonstrate an effect of DFP on the course of PD (including both disease-modifying and symptomatic effects). |
L'objectif principal de l'essai FAIR-PARK II est de démontrer un effet de DFP sur la maladie de Parkinson (incluant à la fois l'effet disease-modifying et les effets symptomatiques). |
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E.2.2 | Secondary objectives of the trial |
1-The disease-modifying effect 2- The global effect on motor and non-motor symptoms 3-Effects on quality of life and autonomy 4-A health economics assessment will be performed via a specific questionnaire and EQ-5D questionnaire 5-A biomarker analysis to assess the biomarkers' potential surrogate value : • MRI,Dopamine transporter (DaT) scan,Transcranial ultrasound • Data from the continuous assessment of PD-relevant domains with an unobtrusive, continuous; quantitative measurement tool • Surrogate marker: Iron metabolism: ferritin ,Ceruloplasmin levels, ceruloplasmin ferroxidase activity, and the ceruloplasmin genotype;the COMT Val158Met polymorphism will be assessed • Heavy metal assays: blood iron zinc,copper,magnesium,chrome,manganese, nickel,lead and cadmium levels, 24-hour urine copper and zinc levels. • Oxidative stress ,A specific biochemistry screen • Vitamins B1,B6,B12, E, A,and C,folates. • Inflammatory factors: tumour necrosis factor alpha and interleukin-6 |
1-L'effet disease-modifying 2- L'effet global sur les symptômes moteurs et non moteurs 3-Les effets sur la qualité de vie et l'autonomie 4-Une évaluation économique sera réalisée par l'intermédiaire d'un questionnaire spécifique et EQ-5D 5-Une analyse des biomarqueurs : • IRM, DATSCAN, échographie transcrânienne • Des données de l’évaluation continue des symptômes liés au parkinson avec un outil ergonomique de mesure quantitative continue • Le métabolisme du fer: la ferritine, les niveaux céruloplasmine, l'activité de la céruloplasmine ferroxydase, et le génotype de céruloplasmine; le polymorphisme COMT Val158Met • analyses de métaux lourds: le sang zinc de fer, de cuivre, de magnésium, de chrome, de manganèse, de nickel, de plomb et de cadmium, cuivre urine de 24 heures et les niveaux de zinc. •Stress oxydatif, un écran spécifique de biochimie • vitamines B1, B6, B12, E, A et C, folates. • Les facteurs inflammatoires: facteur de nécrose tumorale alpha et l'interleukine-6 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult Patients 2. Parkinson’s disease diagnosed according UK Parkinson’s disease Society Brain Bank Clinical Diagnostic Criteria and based on the presence of at least two of the three cardinal features of the disease (rest tremor, bradykinesia and rigidity). If rest tremor is not present, subjects must have unilateral onset of symptoms. 3. Treatment-naïve, i.e. the best population for assessing a disease-modifying effect without the interaction of dopaminergic treatment (no dopaminergic agonists, L-dopa, anticholinergics, monoamine oxidase B inhibitors (e.g. rasagiline) or deep brain stimulation). 4. Patients covered by a Health Insurance System in countries where required by law 5. Written informed consent dated and signed prior to the beginning of any procedures related to the clinical trial
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1. Patient majeur 2. Maladie de Parkinson diagnostiquée selon la UK Parkinson’s disease Society Brain Bank Clinical Diagnostic Criteria et basé sur la présence d’au moins deux des trois signes cardinaux de la maladie (tremblements de repos, bradykinésie et rigidité). Si le tremblement de repos n’est pas présent, les sujets doivent avoir une apparition unilatérale des symptômes. 3. Sans traitement c’est à dire sans aucun traitement pour la maladie de Parkinson (levodopa, agoniste dopaminergique, anticholinergique) y compris inhibiteur de la monoamine oxydase B (rasagiline) et stimulation cérébrale. 4. Patient assuré social dans les pays où cela est requis par la loi. 5. Consentement éclairé daté et signé avant le début de toutes procédures de l’étude. |
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E.4 | Principal exclusion criteria |
1. Disease duration greater than 18 months. 2. Patients with high frequency of comorbidity or vital risks that may reasonably impair life expectancy 3. Subject with handicap required dopaminergic treatment at the inclusion and therefore likely not to bear 9 months without symptomatic treatment 4. Hoehn and Yahr stage 3 or more. 5. Significant cognitive impairment (a Mini Mental State Examination score <24 or an equivalent impairment on a similar scale) or dementia diagnosed in accordance with the Movement Disorders Society criteria (Emre et al., 2007). 6. Atypical or secondary parkinsonism (supranuclear palsy, multisystem atrophy, etc.) or anomalies on MRI suggestive of vascular involvement or significant cortical or subcortical atrophy (i.e. atypical for PD). 7. Progressing axis I psychiatric disorders (psychosis, hallucinations, substance addiction, bipolar disorder, or severe depression), in accordance with the Diagnostic and Statistical Manual of Mental Disorders. 8. Subjects undergoing brain stimulation. 9. Positive HIV serology. 10. Hypersensitivity to deferiprone. 11. Patients with agranulocytosis or with a history of agranulocytosis. 12. Patients taking a treatment at risk of agranulocytosis (clozapine, Closaril®/Leponex®). 13. Patients with anaemia (regardless of the latter's aetiology) or a history of another haematological disease. Haemochromatosis is not an exclusion criterion. 14. Pregnant or breastfeeding women or women of childbearing potential not taking highly effective contraception. 15. Kidney or liver failure. 16. Other serious diseases. 17. Inability to provide informed consent. 18. Participation in another clinical trial within 3 months prior to inclusion in the study 19. Patient who has suffered mild or moderate depressive episode and isn’t in remission and on a stable medication for at least 8 weeks
o Exclusion criteria for the biomarker study and the ancillary study (i) MRI: • Subjects for whom MRI is contraindicated (metal objects in the body, severe claustrophobia, pacemaker, incompatible surgical material). • Very severe rest tremor, which could induce MRI artefacts. (ii) Lumbar puncture: • Blood coagulation disorders, antiplatelet drugs or anticoagulants. • Intracranial hypertension. (iii) Contraindications to nitrous oxide: • Ventilation with FiO2 >50%, emphysema or pneumothorax • Altered states of consciousness, non-cooperative patient (need to stop the nitrous oxide)
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1. Durée d’évolution de la maladie de plus de 18 mois 2. Les patients ayant un risque accru de comorbidité ou risques vitaux qui peuvent raisonnablement nuire à l'espérance de vie 3. Patient avec un handicap nécessitant un traitement dopaminergique à l'inclusion et donc susceptible de ne pas supporter 9 mois sans traitement symptomatique 4. Stade de Hoehn et Yahr de 3 ou plus. 5. Un trouble cognitif significatif (score MOCA <24) ou une démence diagnostiqué selon les critères de la Movement Disorders Society criteria (Emre et al., 2007). 6. Syndrome parkinsonien atypique ou secondaire (paralysie supra nucléaire, atrophie multi systématisée, etc.) ou anomalies sur l’IRM suggérant une participation vasculaire franche (infarctus ou leuco encéphalopathie extensive) ou une atrophie corticale focale importante. 7. Troubles psychiatriques progressifs de l’axe I (psychose, hallucinations, addiction sévère à une substance, maladie bipolaire, ou dépression sévère), selon les critères du Diagnostic and Statistical Manual of Mental Disorders. 8. Patients ayant une stimulation cérébrale. 9. Sérologie positive au VIH. 10. Hypersensibilité aux chélateurs de fer. 11. Patients ayant une agranulocytose ou des antécédents d’agranulocytose 12. Patients prenant un traitement à risque d’agranulocytose (clozapine, Closaril®/Leponex®). 13. Patients ayant une anémie (quelque soit l’étiologie) ou un antécédent de maladie hématologique. L’hémochromatose n’est pas un critère d’exclusion. 14. Femme enceintes ou allaitantes ou femmes en âge de procréer sans contraception efficace. 15. Insuffisance rénale ou hépatique. 16. Autres maladies graves. 17. Incapacité de donner un consentement éclairé 18. Participation à un autre essai clinique dans 3 mois avant l'inclusion dans l'étude 19. Patient qui a subi un épisode dépressif léger ou modéré ET qui n’est pas en rémission ET qui n’a pas de traitement stable pendant au moins 8 semaines Critères d’exclusion pour les études de biomarqueurs et ancillaires (i) IRM • Sujets ayant une contre-indication classique à l’IRM (corps étrangers métalliques, claustrophobie sévère, pacemaker, matériel chirurgical non compatible.). • Un tremblement de repos très sévère qui pourrait induire des artefacts à l’IRM. (ii) Ponction lombaire • Pathologie de la coagulation, traitement anticoagulant, traitement antiagrégant plaquettaire. • Hypertension intracraniale. (iii) Contre-indications à l’oxyde nitrique • Ventilation avec une FiO2 >50%, emphysème ou pneumothorax • Altération de l’état de conscience (impose l’arrêt) • patients non-coopératif (impose l’arrêt) |
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E.5 End points |
E.5.1 | Primary end point(s) |
the change in the total MDS-UPDRS |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
week 0, week12; week24; week36; week40 |
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E.5.2 | Secondary end point(s) |
(i) MDS-UPDRS score between baseline and week 40 (ii) MDS-UPDRS (part I: cognition and behaviour; part II: activities of daily living; part III: motor handicap; part IV: fluctuations), the Stand Walk Sit test, overall cognitive status (score in the Montreal Cognitive Assessment) between baseline and week 36; and between baseline and week 40 (iii) Effects on quality of life and autonomy will be analyzed as the change in the Parkinson’s Disease Quality of Life (PDQ-39, via a 39-item self-questionnaire) and the Clinical Global Impression scored by the examiner and the patient between baseline and week 36, and between baseline and week 40 f (iv) A health economics assessment will be performed via a specific questionnaire and EQ-5D questionnaire (It provides a simple descriptive profile and a single index value for health status) between baseline and week 36, and between baseline and week 40 (v) A biomarker analysis to assess the biomarkers' potential surrogate value -MRI - Dopamine transporter (DaT) scan - Transcranial ultrasound - Data from the continuous assessment of PD-relevant domains with an unobtrusive, continuous -A specific biochemistry screen |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 24 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial 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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |