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

NCT00627588 | Completed Phase 1 DMC

• 2 other identifiers: PS-001-07EudraCT Number: 2007-001109-26
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Parkinson's Disease

Keywords

ProSavin; Parkinson's Disease; Gene Therapy

Outcome Measures

Primary Outcomes (1)

• Safety as measured by the number and severity of Adverse Events

  1 year

Secondary Outcomes (1)

• Efficacy as measured by the UPDRS

  6 months

Study Arms (2)

Dose Evaluation

EXPERIMENTAL

To assess the safety and efficacy of up to three dose levels of ProSavin

Biological: ProSavin

Sham element

SHAM COMPARATOR

The potential use of sham comparator to confirm efficacy

Biological: ProSavin

Interventions

ProSavin BIOLOGICAL

ProSavin is a gene therapy designed to delivery three key enzymes involved in the synthesis of dopamine

Dose Evaluation

Eligibility Criteria

• Age: 48 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give written Informed Consent
• Diagnosed with bilateral idiopathic PD
• Diagnosis of PD \> five years, using diagnostic criteria from core assessment program for surgical interventional therapies CAPSIT (1999)
• Males/females between 48 and 65 years
• Women must be postmenopausal, with last menstrual period being over two years ago
• 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
• Response to L-DOPA where an increase in dose is unacceptable to the patient due to potentiating the fluctuations in motor functions
• Hoehn and Yahr stage 3 and 4
• UPDRS (Part III) of between 20 and 60 in the "OFF" state
• Stable dosing of PD medication, including L-DOPA, for six weeks prior to surgery
• Positive response to dopaminergic therapy as defined by a 50% improvement in UPDRS (Part III) between the "OFF" and "ON" states
• Presence of motor fluctuations
• Willing to have current treatment withdrawn for up to 24 hours prior to surgery therefore being in an "OFF" state for surgery
• 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
• Affiliated with the French social security health care system (Patients enrolled in France only)

You may not qualify if:

• Major surgery within the 28 days prior to enrolment
• Severe disabling dyskinesias \> or = 51% of the day as defined by the UPDRS (Part IV)
• History of psychosis or current treatment with dopamine blocking agents of any kind
• 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
• 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
• 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
• Life-threatening illness unrelated to PD
• History of stereotactic or other surgery for the treatment of PD
• Premenopausal women
• Alcohol or other substance abuse
• Clinically significant laboratory test abnormalities, including full blood count, chemistry panel, liver function tests, electrocardiogram (ECG), Chest X rays
• Any contraindication for undergoing an MRI scan of the head
• Intercurrent illness or infection 28 days prior to enrolment
• 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)
• Prior regular exposure to neuroleptic agents

Sponsors & Collaborators

• Oxford BioMedica: lead

Study Sites (2)

Henri Mondor Hospital

Paris, France

Location

Addenbrookes Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Related Publications (1)

• Palfi S, Gurruchaga JM, Ralph GS, Lepetit H, Lavisse S, Buttery PC, Watts C, Miskin J, Kelleher M, Deeley S, Iwamuro H, Lefaucheur JP, Thiriez C, Fenelon G, Lucas C, Brugieres P, Gabriel I, Abhay K, Drouot X, Tani N, Kas A, Ghaleh B, Le Corvoisier P, Dolphin P, Breen DP, Mason S, Guzman NV, Mazarakis ND, Radcliffe PA, Harrop R, Kingsman SM, Rascol O, Naylor S, Barker RA, Hantraye P, Remy P, Cesaro P, Mitrophanous KA. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial. Lancet. 2014 Mar 29;383(9923):1138-46. doi: 10.1016/S0140-6736(13)61939-X. Epub 2014 Jan 10.

  PMID: 24412048 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Stephane Palfi, Professor

  Henri Mondor University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2008
• First Posted: March 3, 2008
• Study Start: January 1, 2008
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: May 13, 2013

Record last verified: 2013-05

Locations

GB (1); FR (1)