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

Phase 1
Terminated
Conditions
Parkinson Disease
Interventions
Other: Imitation Surgical Procedure (ISP)
Registration Number
NCT03720418
Lead Sponsor
Sio Gene Therapies
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).

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
6
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
OXB-102 Dose Level 2OXB-102OXB-102 Dose Level 2 Single Administration (Part A: open-label)
OXB-102 Dose Level 3OXB-102OXB-102 Dose Level 3 Single Administration (Part A: open-label)
Imitation Surgical ProcedureImitation Surgical Procedure (ISP)General anesthesia with bilateral skin incisions (Part B: double-blind)
OXB-102 Selected DoseOXB-102Selected Dose of OXB-102 Single Administration (Part B: double-blind)
OXB-102 Dose Level 1OXB-102OXB-102 Dose Level 1 Single Administration (Part A: open-label)
Primary Outcome Measures
NameTimeMethod
Safety of OXB-102 as measured by changes in vital signs3 months timepoint

Number of clinically significant changes in vital signs

Safety of OXB-102 as measured by changes in clinical laboratory analysis3 months timepoint

Number of clinically significant changes in clinical laboratory analysis

Safety of OXB-102 as measured by changes in brain MRI findings3 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 events3 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

Safety of OXB-102 as measured by changes in physical examination3 months timepoint

Number of clinically significant changes in physical examination

Secondary Outcome Measures
NameTimeMethod
Change in Unified Parkinson's Disease Rating Scale (UPDRS) scores defined in "OFF" and "ON" medication statesBaseline to 6 months
Change in dyskinesia rating scale scoreBaseline to 6 months
Change in "OFF" time during waking day compared to baseline as assessed by participant diariesBaseline to 6 months

Trial Locations

Locations (3)

Service de Neurochirurgie, Hôpital Henri Mondor

🇫🇷

Créteil, France

University of Cambridge, Centre for Brain Repair

🇬🇧

Cambridge, Cambridgeshire, United Kingdom

The National Hospital for Neurology and Neurosurgery

🇬🇧

London, United Kingdom

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