Phase I/II Study of the Safety, Efficacy and Dose Evaluation of ProSavin for the Treatment of Bilateral Idiopathic Parkinson's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Oxford BioMedica
ClinicalTrials.gov Identifier:
NCT00627588
First received: January 31, 2008
Last updated: May 9, 2013
Last verified: May 2013
  Purpose

The primary objectives of the trial are to assess the safety and efficacy of ProSavin.

Patients in the trial will have been diagnosed with Parkinson's disease and will be failing on current treatment with L-DOPA but they will not have progressed to drug-induced dyskinesias. The first stage is an open-label dose escalation to evaluate up to three dose levels of ProSavin in cohorts of three patients each. Following a recommendation by the DMC the study may proceed to the second stage of the trial, a further 12 patients will be recruited to confirm efficacy of the optimal dose in the randomized phase of the study.

The efficacy of ProSavin will be assessed using the Unified Parkinson's Disease Rating Score (UPDRS). Patients will be monitored at regular intervals, with the primary endpoint being an efficacy assessment at six months after treatment. The secondary objective of the trial is to asses the extent to which patients' current therapy (L-DOPA) can be reduced following administration of ProSavin.


Condition Intervention Phase
Parkinson's Disease
Biological: ProSavin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of the Safety, Efficacy and Dose Evaluation of ProSavin®, Administered Using Stereotactic Injection to the Striatum of Patients With Bilateral, Idiopathic Parkinson's Disease.

Resource links provided by NLM:


Further study details as provided by Oxford BioMedica:

Primary Outcome Measures:
  • Safety as measured by the number and severity of Adverse Events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy as measured by the UPDRS [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 15
Study Start Date: January 2008
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Evaluation
To assess the safety and efficacy of up to three dose levels of ProSavin
Biological: ProSavin
ProSavin is a gene therapy designed to delivery three key enzymes involved in the synthesis of dopamine
Sham Comparator: Sham element
The potential use of sham comparator to confirm efficacy
Biological: ProSavin
ProSavin is a gene therapy designed to delivery three key enzymes involved in the synthesis of dopamine

  Eligibility

Ages Eligible for Study:   48 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to give written Informed Consent
  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 postmenopausal, with last menstrual period being over two years ago
  6. Male patients must agree to use at least two methods of contraception for at least 3 months following ProSavin administration if they and 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, for six 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 principal 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 (Patients enrolled in France only)

Exclusion Criteria:

  1. Major surgery within the 28 days prior to enrolment
  2. Severe disabling dyskinesias > or = 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 seretonergic therapies and those that do not target the dopaminergic pathways
  5. Prior treatment with tolcapone within the six months prior to enrollment into the study, due to its ability to modify dopaminergic pathways in 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 arteriovenous 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 enrollment
  17. Contraindications to use of anaesthesia
  18. Treated with dopaminergic antagonists six months prior to screening
  19. Concurrent antiretroviral 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 of anticipated treatment with anticoagulant therapy or the use of anticoagulation therapy within the four weeks prior to surgery
  24. Diagnosis of multiple systems atrophy (MSA) following assessment of the autonomic nervous systems 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. Patient unable to adhere to their prescribed Parkinson's disease treatment regime.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00627588

Locations
France
Henri Mondor Hospital
Paris, France
United Kingdom
Addenbrookes Hospital
Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
Sponsors and Collaborators
Oxford BioMedica
Investigators
Principal Investigator: Stephane Palfi, Professor Henri Mondor Hospital
  More Information

No publications provided by Oxford BioMedica

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Oxford BioMedica
ClinicalTrials.gov Identifier: NCT00627588     History of Changes
Other Study ID Numbers: PS-001-07, EudraCT Number: 2007-001109-26
Study First Received: January 31, 2008
Last Updated: May 9, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Oxford BioMedica:
ProSavin
Parkinson's Disease
Gene Therapy

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on August 21, 2014