Parkinson Disease
Conditions
Keywords
Parkinson's disease, Gene therapy, OXB-102, AXO-Lenti-PD
Brief summary
This study consists of two parts. Part A will evaluate the safety and tolerability of multiple doses of OXB-102 (AXO-Lenti-PD) in participants with Parkinson's disease. Part B will assess the safety and efficacy of the selected dose of OXB-102 in participants with Parkinson's disease.
Detailed description
This study consists of two parts. Part A is an open-label dose-escalation phase in which participants are enrolled in cohorts and will receive one of approximately three escalating doses of OXB-102 (AXO-Lenti-PD). Part B is a randomized, double-blind phase in which participants will be randomized to either an active group receiving the selected dose from Part A, or to a control group receiving an imitation surgical procedure (ISP).
Interventions
DRUGOXB-102
Neurosurgical delivery of OXB-102 (gene therapy) to the putamen
OTHERImitation Surgical Procedure (ISP)
Participants randomized to the control group in Part B will receive an ISP
Sponsors
Sio Gene Therapies
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Study Part A open-label and Study Part B randomized, double-blind
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Diagnosed with bilateral idiopathic PD 2. Males/females between 30 and 70 years at the time of surgery 3. Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) score of between 30 and 60 in the OFF medication state 4. Presence of motor fluctuations and/or dyskinetic movement 5. Candidate for surgical intervention 6. Hoehn and Yahr (H&Y) Stage 3 or 4 in the OFF medication state 7. Stable dosing of PD medication, including L-DOPA, for four weeks prior to screening with Levodopa equivalent daily dose (LEDD) of at least 900 mg Key
Exclusion criteria
1. History of psychosis or current treatment with dopamine blocking agents and prior regular exposure to antipsychotic agents 2. History of stereotactic or other surgery for the treatment of PD, including Deep Brain Stimulation (DBS) 3. Participation in a prior cell or gene transfer therapy study 4. Contraindications to use of anaesthesia 5. Current or anticipated treatment with anticoagulant therapy or the use of anticoagulation therapy that cannot be temporarily stopped around the time of surgery 6. Diagnosis of multiple system atrophy 7. Abnormal MRI findings such as mega cisterna, septum pellucidum, signs of severe cortical or subcortical atrophy, brain tumours, vascular diseases, trauma or arteriovenous malformations 8. Presence of dementia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of OXB-102 as measured by changes in physical examination | 3 months timepoint | Number of clinically significant changes in physical examination |
| Safety of OXB-102 as measured by changes in clinical laboratory analysis | 3 months timepoint | Number of clinically significant changes in clinical laboratory analysis |
| Safety of OXB-102 as measured by changes in vital signs | 3 months timepoint | Number of clinically significant changes in vital signs |
| Safety of OXB-102 as measured by changes in brain MRI findings | 3 months timepoint | Number of clinically significant changes in brain MRI findings |
| Safety of OXB-102 as measured by incidence of treatment emergent adverse events and serious adverse events | 3 months timepoint | Treatment emergent adverse events and serious adverse events will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for severity |
Secondary
| Measure | Time frame |
|---|---|
| Change in OFF time during waking day compared to baseline as assessed by participant diaries | Baseline to 6 months |
| Change in dyskinesia rating scale score | Baseline to 6 months |
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) scores defined in OFF and ON medication states | Baseline to 6 months |
Countries
France, United Kingdom
Outcome results
None listed