Study of OXB-102 (AXO-Lenti-PD) in Patients With Bilateral, Idiopathic Parkinson's Disease

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Phase I/II Safety and Dose Evaluation Study of OXB-102 (AXO-Lenti-PD) in Patients With Bilateral Idiopathic Parkinson's Disease (SUNRISE-PD)

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: OXB-102
* Other: Imitation Surgical Procedure (ISP)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosed with bilateral idiopathic PD Males/females between 30 and 70 years at the time of surgery Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) score of between 30 and 60 in the OFF medication state Presence of motor fluctuations and/or dyskinetic movement Candidate for surgical intervention Hoehn and Yahr (H&Y) Stage 3 or 4 in the OFF medication state 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: History of psychosis or current treatment with dopamine blocking agents and prior regular exposure to antipsychotic agents History of stereotactic or other surgery for the treatment of PD, including Deep Brain Stimulation (DBS) Participation in a prior cell or gene transfer therapy study Contraindications to use of anaesthesia Current or anticipated treatment with anticoagulant therapy or the use of anticoagulation therapy that cannot be temporarily stopped around the time of surgery Diagnosis of multiple system atrophy Abnormal MRI findings such as mega cisterna, septum pellucidum, signs of severe cortical or subcortical atrophy, brain tumours, vascular diseases, trauma or arteriovenous malformations Presence of dementia

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OXB-102 Dose Level 1<br>OXB-102 Dose Level 1 Single Administration (Part A: open-label) | Drug: OXB-102<br>* Neurosurgical delivery of OXB-102 (gene therapy) to the putamen<br>* Other names: AXO-Lenti-PD;|
| Experimental: OXB-102 Dose Level 2<br>OXB-102 Dose Level 2 Single Administration (Part A: open-label) | Drug: OXB-102<br>* Neurosurgical delivery of OXB-102 (gene therapy) to the putamen<br>* Other names: AXO-Lenti-PD;|
| Experimental: OXB-102 Dose Level 3<br>OXB-102 Dose Level 3 Single Administration (Part A: open-label) | Drug: OXB-102<br>* Neurosurgical delivery of OXB-102 (gene therapy) to the putamen<br>* Other names: AXO-Lenti-PD;|
| Experimental: OXB-102 Selected Dose<br>Selected Dose of OXB-102 Single Administration (Part B: double-blind) | Drug: OXB-102<br>* Neurosurgical delivery of OXB-102 (gene therapy) to the putamen<br>* Other names: AXO-Lenti-PD;|
| Sham Comparator: Imitation Surgical Procedure<br>General anesthesia with bilateral skin incisions (Part B: double-blind) | Other: Imitation Surgical Procedure (ISP)<br>* Participants randomized to the control group in Part B will receive an ISP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of OXB-102 as measured by incidence of treatment emergent adverse events and serious adverse events | 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 | 3 months timepoint | 
| Safety of OXB-102 as measured by changes in clinical laboratory analysis | Number of clinically significant changes in clinical laboratory analysis | 3 months timepoint | 
| Safety of OXB-102 as measured by changes in vital signs | Number of clinically significant changes in vital signs | 3 months timepoint | 
| Safety of OXB-102 as measured by changes in brain MRI findings | Number of clinically significant changes in brain MRI findings | 3 months timepoint | 
| Safety of OXB-102 as measured by changes in physical examination | Number of clinically significant changes in physical examination | 3 months timepoint | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) scores defined in OFF and ON medication states |  | Baseline to 6 months | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Gene therapy, OXB-102, AXO-Lenti-PD