E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with bilateral, idiopathic Parkinson's Disease |
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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 |
To assess the safety of ProSavin, injected bilaterally directly into the post-commissural putamen of patients with bilateral idiopathic Parkinson's disease. Up to three dose levels will be assessed
To assess the patients for clinical efficacy following ProSavin administration |
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E.2.2 | Secondary objectives of the trial |
To assess the extent of L-DOPA therapy reduction following administration of ProSavin |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated written informed consent obtained from the patient and/or the patient’s legally acceptable representative, if applicable, in accordance with the local regulations 2. Diagnosed with bilateral idiopathic PD 3. Diagnosis of PD > five years, using diagnostic criteria from core assessment program for surgical interventional therapies CAPSIT (1999) 4. Males/females between 48 and 65 years 5. Women must be surgically sterile or postmenopausal, with last menstrual period being over two years ago 6. Male patients must be surgically sterile or agree to use two forms of contraception, including one barrier method for at least three months following ProSavin administration if their partner is of child-bearing capacity 7. Response to L-DOPA where an increase in dose is unacceptable to the patient due to potentiating the fluctuations in motor functions 8. Hoehn and Yahr stage 3 and 4 9. UPDRS (Part III) of between 20 and 60 in the “OFF” state 10. Stable dosing of PD medication, including L-DOPA, and any treatments (if required) for sleep apnea syndrome for four weeks prior to surgery 11. Positive response to dopaminergic therapy as defined by a 50% improvement in UPDRS (Part III) between the “OFF” and “ON” states 12. Presence of motor fluctuations 13. Willing to have current treatment withdrawn for up to 24 hours prior to surgery therefore being in an “OFF” state for surgery 14. Willing to have their L-DOPA dosage reduced/withdrawn at the discretion of the principle investigator (PI) at regular intervals following surgery to allow assessment of ProSavin in the absence of concomitant anti-parkinsonian medication 15. Affiliated with the French social security health care system (French patients only) |
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E.4 | Principal exclusion criteria |
1. Major surgery within the 28 days prior to enrolment 2. Severe disabling dyskinesias ≥ 51% of the day as defined by the UPDRS (Part IV) 3. History of psychosis or current treatment with dopamine blocking agents of any kind 4. Severe depression as defined by a BDI score of >16. Any treatment for depression should be limited to serotonergic therapies and those that do not target the dopaminergic pathways 5. Prior treatment with tolcapone, within the six months prior to enrolment into the study, due to its ability to modify dopaminergic pathways within the brain 6. History of epilepsy or any other co-morbid condition that the Investigator believes presents an unacceptable health risk to the patient in conjunction with the procedures in this protocol 7. Life-threatening illness unrelated to PD 8. History of stereotactic or other surgery for the treatment of PD 9. Premenopausal women 10. Alcohol or other substance abuse 11. Clinically significant laboratory test abnormalities, including full blood count, chemistry panel, liver function tests, electrocardiogram (ECG), Chest X rays 12. Any contraindication for undergoing an MRI scan of the head 13. Intercurrent illness or infection 28 days prior to enrolment 14. Abnormal MRI findings such as mega cisterna, septum pellucidum, signs of severe cortical or subcortical atrophy, brain tumours, vascular diseases, trauma or areteriovenous malformations (AVM) 15. Prior regular exposure to neuroleptic agents 16. History of treatment with any agent that may induce PD or PD symptoms within the last three months prior to enrolment 17. Contraindications to use of anaesthesia 18. Treated with dopaminergic antagonists six months prior to screening 19. Concurrent anti-retroviral therapy that would inactivate the investigational agent 20. History of any investigational agent within 28 days prior to ProSavin administration 21. Participation in a prior gene transfer therapy study 22. Enrolment in any other clinical study, for any condition, including those relating to PD, throughout the duration of the ProSavin study 23. Current or anticipated treatment with anticoagulant therapy or the use of anticoagulation therapy within the four weeks prior to surgery 24. Diagnosis of multiple system atrophy (MSA) following assessment of the autonomic nervous system function (e.g. blood pressure, difficulty in urinating and sexual activity) and MRI during the screening process 25. Administration of subcutaneous rescue remedy apomorphine 26. Patients unable to adhere to their prescribed PD medication regime |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety: The number and severity of any adverse events associated with ProSavin administration, including the incidence of dyskinesias.
Efficacy: The patients’ responses to ProSavin administration by assessment using the UPDRS Part III, six months following surgery
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Stage 1 is uncontrolled and open. Stage 2 is randomised, blinded and controlled. |
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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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | Information not present in EudraCT |
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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When all patients have completed the 12 month visit. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |