Parkinson's DiseasePhase 1/2NCT00627588
Phase I/II Study of the Safety, Efficacy and Dose Evaluation of ProSavin for the Treatment of Bilateral Idiopathic Parkinson's Disease
A Phase 1/2 study testing ProSavin in people with Parkinson's Disease, run by Oxford BioMedica at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 48 to 65 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- ProSavin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jan 2008to Aug 2012
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 48 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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- Willing to have current treatment withdrawn for up to 24 hours prior to surgery therefore being in an "OFF" state for surgery
- Willing to have their L-DOPA dosage reduced/withdrawn at the discretion of the principal investigator (PI) at regular intervals following surgery to allow assessment of ProSavin in the absence of concomitant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)
Who cannot join
- 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
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- 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
- History of treatment with any agent that may induce PD or PD symptoms within the last three months prior to enrollment
- Contraindications to use of anaesthesia
- Treated with dopaminergic antagonists six months prior to screening
- Concurrent antiretroviral therapy that would inactivate the investigational agent
- History of any investigational agent within 28 days prior to ProSavin administration
- Participation in a prior gene transfer therapy study
- Enrolment in any other clinical study, for any condition, including those relating to PD, throughout the duration of the ProSavin study
- Current of anticipated treatment with anticoagulant therapy or the use of anticoagulation therapy within the four weeks prior to surgery
- 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
- Administration of subcutaneous rescue remedy apomorphine
- Patient unable to adhere to their prescribed Parkinson's disease treatment regime.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United Kingdom1 site
Addenbrookes Hospital
Cambridge, Cambridgeshire, CB2 0QQ
About this study
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.
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
- Being tested
- ProSavin
- Keywords
- ProSavin, Parkinson's Disease, Gene Therapy
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProSavinBiological
ProSavin is a gene therapy designed to delivery three key enzymes involved in the synthesis of dopamine
ProSavinBiological
ProSavin is a gene therapy designed to delivery three key enzymes involved in the synthesis of dopamine
| Study group | Role | What they receive |
|---|---|---|
| Dose Evaluation | Experimental | To assess the safety and efficacy of up to three dose levels of ProSavin Receives: Biological: ProSavin |
| Sham element | Sham comparator | The potential use of sham comparator to confirm efficacy Receives: Biological: ProSavin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as measured by the number and severity of Adverse Events
Measured: 1 year
Secondary outcomes (1)
Efficacy as measured by the UPDRS
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2008 (estimated)
- Study startJan 2008
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oxford BioMedica
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephane Palfi, Professor, Principal investigator, Henri Mondor University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00627588
- Sponsor's protocol ID
- PS-001-07
- Other IDs
- EudraCT Number: 2007-001109-26
- Status last verified
- May 2013
- First submitted
- 31 Jan 2008
- Last updated
- 13 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24412048
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00627588
- Acronym / sponsor ID
- PS-001-07
- Conditions
- Parkinson's Disease
- Keywords
- ProSavin, Parkinson's Disease, Gene Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Oxford BioMedicaIndustry (pharma, biotech, devices)
- Study start
- Jan 2008
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 3 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Evaluation | Experimental | Biological: ProSavinTo assess the safety and efficacy of up to three dose levels of ProSavin |
| Sham element | Sham comparator | Biological: ProSavinThe potential use of sham comparator to confirm efficacy |
Who may qualify
- Ages
- 48 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProSavinProSavin is a gene therapy designed to delivery three key enzymes involved in the synthesis of dopamine | Biological | Dose Evaluation |
| ProSavinProSavin is a gene therapy designed to delivery three key enzymes involved in the synthesis of dopamine | Biological | Sham element |
Primary outcome
Safety as measured by the number and severity of Adverse Events
Time frame: 1 year
1 secondary outcome
Efficacy as measured by the UPDRS
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2013.
- Derived from this study: PubMed 24412048Palfi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephane Palfi, Professor principal investigator
Henri Mondor University Hospital
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ProSavin in people with Parkinson's Disease, run by Oxford BioMedica at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as measured by the number and severity of Adverse Events (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00627588, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2013.