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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: OXB-102; Other: Imitation Surgical Procedure (ISP)

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).

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94010
    • Service de Neurochirurgie, Hopital Henri Mondor
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • The National Hospital for Neurology and Neurosurgery
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0PY,
      • University of Cambridge, Centre for Brain Repair

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Sio Gene Therapies
• Investigators: Study Director: Erika De Boever, DDS, PhD, Sio Gene Therapies

Publications and helpful links

General Publications

• McFarthing K, Prakash N, Simuni T. CLINICAL TRIAL HIGHLIGHTS: 1. GENE THERAPY FOR PARKINSON'S, 2. PHASE 3 STUDY IN FOCUS - INTEC PHARMA'S ACCORDION PILL, 3. CLINICAL TRIALS RESOURCES. J Parkinsons Dis. 2019;9(2):251-264. doi: 10.3233/JPD-199001. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2018
• Primary Completion (Actual): April 12, 2022
• Study Completion (Actual): April 12, 2022

Study Registration Dates

• First Submitted: October 16, 2018
• First Submitted That Met QC Criteria: October 24, 2018
• First Posted (Actual): October 25, 2018

Study Record Updates

• Last Update Posted (Actual): May 3, 2022
• Last Update Submitted That Met QC Criteria: April 27, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Parkinson's disease; Gene therapy; OXB-102; AXO-Lenti-PD
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: OXB-102-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No