New therapeutic strategy in Parkinson’s disease

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2015-003679-31-AT
• Date of registration: 11/01/2016
• Prospective Registration: Yes
• Primary sponsor: Centre Hospitalier Régional et Universitaire de Lille
• Public title: New therapeutic strategy in Parkinson’s disease
• Scientific title: Conservative iron chelation as a disease-modifying strategy in Parkinson’s disease - FAIRPARK II
• Date of first enrolment: 06/04/2016
• Target sample size: 372
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003679-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Czech Republic, France, Germany, Netherlands, Portugal, Spain, United Kingdom

Contacts

• Name: Katarzyna Wachowicz
• Affiliation: Medizinische Universität Innsbruck

• Name: Katarzyna Wachowicz
• Affiliation: Medizinische Universität Innsbruck

Key inclusion & exclusion criteria

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


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 169
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 169

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 neutropenia
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 >130kg


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)




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

De Novo Parkinson’s disease

Intervention(s)

Product Name: Deferiprone DR
Pharmaceutical Form: Tablet
INN or Proposed INN: DEFERIPRONE
CAS Number: 30652-11-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 1- Disease modifying effect
2- Demonstrate the feasibility of a multi site european clinical trial of a potential PD treatment with a demonstrated safety profile
3- Fund the larger scale investigation of DFP in PD patients
4- Investigate clinical, radiological, biological and genetic biomarkers of PD progression in response of DFP
5- Bring the first data of DFP's potential real-worl benefits based upon the drug's impact on health economics aspects and the continuous monitoring of motor and non-motor handicap at home.
6- Expedite the availability of disease-modifying treatments to PD patients. Based upon our demonstration of efficacy and safety of conservative iron chelation with the only available and prototyoe drug, DFP
7- To describe the effect of DFP on the disease progression, taking into account the drop out rate with a combined criterion of disease progression measured by the total score of the MDS-UPDRS and the dropout because of disease worsening.

Timepoint(s) of evaluation of this end point: week 0, week12; week24; week36; week40

Main Objective: 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).

Primary end point(s): the change in the total MDS-UPDRS

Secondary Outcome(s)

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

Timepoint(s) of evaluation of this end point: week 0, week36; week40

Secondary ID(s)

2015_22

Source(s) of Monetary Support

European Union’s Horizon 2020 research and innovation programme

Ethics review

Status: Approved
Approval date: 06/04/2016
Contact: