Gene Therapy for Parkison Disease: RESTORE-1 NBIb-1817 (VY-AADC) Clinical Update

Clinical Trial Design

RESTORE-1 (Phase 2 Clinical Study) (NCT03562494): Ongoing

A randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of VY-AADC for the treatment of Parkinson’s disease in 75-100 patients (each trial) with motor fluctuations that are refractory to medical management. 

Population: PD diagnosis > 4 yrs, are not responding adequately to oral medications, and have > 3 hours of OFF time. Randomized (1:1) to one-time administration of VY-AADC (for a total dose of up to 2.5×1012 vector genomes) or placebo surgery. 

Experimental Treatment: VY-AADC02 (NBIb-1817)
A single administration of up to 3.6 x 10^12 vector genomes (vg) of VY-AADC02

Adeno-associated viral vector serotype 2 encoding human aromatic L-amino acid decarboxylase (AAV2- hAADC) infusion into the brain
NATIVE
Primary Outcome Measures :
Change in ON time without troublesome dyskinesia as recorded by participant in Parkinson's Disease (PD) diary [ Time Frame: Baseline to Day 360 ]

Secondary Outcome Measures :
Change in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III score in the OFF state [ Time Frame: Baseline to Day 360 ]

Change in MDS-UPDRS II score [ Time Frame: Baseline to Day 360 ]

Other Outcome Measures:
Safety outcome measured by treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), changes in vital signs and clinical laboratory analysis, and immunogenicity [ Time Frame: Baseline to Day 360 ]
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PD-1101, a Phase Ib open-label, three-year efficacy, and safety study showed long term efficacy (Update date from 3 years open-labeled follow-up study) Sept 11-2020

- one-time treatment with investigational gene therapy, NBIb-1817 (VY-AADC),

- showed a sustained improvement in motor function including greater "On" time without troublesome dyskinesia, 

- reduction in Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores, and 

- reduction in the amount of medications in patients with Parkinson's disease. In the PD-1101 study, 

- NBIb-1817 reduced average "Off" time by up to -1.91 hours and improved average "On" time without troublesome dyskinesia by up to +2.23 hours in patients with advanced Parkinson's disease after three years across three cohorts. 

- In addition, 14 out of 15 patients treated with NBIb-1817 continued to show an improvement in disease staging after three years, as assessed by the modified Hoehn & Yahr scale.

Reference: Voyager Therapeutics and Neurocine Bioscience Press Release

Therapeutic Approach
Dose-Dependent Increase in AADC Enzyme Activity in Phase 1 Study





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