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). |
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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 |
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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 The Movement Disorder Society Clinical Diagnotic Criteria for Parkinson's Disease (PD). 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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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 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. Due to the high risk of agranulocytosis caused by the IMP and the unknown mechanism by which this agranulocytosis is induced, it is not allowed to combine Deferiprone with other medicinal products causing agranulocytosis (as described in the IB). Such medicinal products are the already mentioned clozapine and also some NSAIDs (e.g. Phenylbutazone or Metamizole), antithyroid agents, sulfonamide antibiotics or metothrexate. 10. A history of relapsing neurotropenia 11. Hypersensitivity to deferiprone. 12. Patients with agranulocytosis or with a history of agranulocytosis. 13. Patients taking a treatment at risk of agranulocytosis (clozapine, Closaril®/Leponex®). 14. Patients with anaemia (regardless of the latter's aetiology) or a history of another haematological disease. Haemochromatosis is not an exclusion criterion. 15. Pregnant or breastfeeding women or women of childbearing potential not taking highly effective contraception. 16. Kidney or liver failure. 17. Other serious diseases. 18. Inability to provide informed consent. 19. Participation in another clinical trial with investigational medicinal product within 3 months prior to inclusion in the study 20. Patient who has suffered mild or moderate depressive episode and isn’t in remission and on a stable medication for at least 8 weeks 21. Patient > 130 kg 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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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 | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |