Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson's Disease

NCT03065192 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PD-1102
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

Brief Summary

Safety and efficacy of AADC gene transfer in participants with Parkinson's disease.

Conditions

Idiopathic Parkinson's Disease; Parkinson's Disease; Basal Ganglia Disease; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Nervous System Diseases; Neurodegenerative Diseases; Parkinsonian Disorders

Keywords

Gene Therapy; PD; Parkinson's Disease; Aromatic L- Amino Acid Decarboxylase; AADC; AAV2-AADC; AAV2; Viral Vector; Gene Transfer; MRI; PET; VY-AADC01

Outcome Measures

Primary Outcomes (5)

• Grading of adverse Events/Serious Adverse Events (AE's/SAE's)

  Grading will be assessed using NCI CTCAE, version 4.03.

  Baseline to 3 Years After Gene Transfer

• Magnetic Resonance Imaging (MRI)

  Safety of VY-AADC01 will be assessed by any clinically significant abnormalities on MRI scans as compared to Baseline.

  Baseline to 3 Years After Gene Transfer

• Routine physical examinations

  Safety of VY-AADC01 will be assessed by routine physical examinations.

  Baseline to 3 Years After Gene Transfer

• Routine clinical laboratory analysis

  Safety of VY-AADC01 will be assessed by routine clinical laboratory analysis.

  Baseline to 3 Years After Gene Transfer

• Change in Columbia-Suicide Severity Rating Scale (C-SSRS) results

  C-SSRS is a standardized suicidal rating system.

  Baseline to 3 Years After Gene Transfer

Secondary Outcomes (16)

• Change in Parkinson's medications

  Baseline to 3 Years After Gene Transfer

• Change in motor function using Parkinson Disease Diaries

  Baseline to 3 Years After Gene Transfer

• Change in motor function using a Stand-Walk-Sit Test

  Baseline to 3 Years After Gene Transfer

• Change in motor function using Modified Hoehn and Yahr Scale

  Baseline to 3 Years After Gene Transfer

• Change in motor function using Unified Parkinson's Disease Rating Scale (UPDRS)

  Baseline to 3 Years After Gene Transfer

Study Arms (1)

VY-AADC01 Single Dose

EXPERIMENTAL

9.4 x 10\^12 vector genomes of VY-AADC01

Drug: VY-AADC01

Interventions

VY-AADC01 DRUG

Single dose, neurosurgically infused, bilaterally into the striatum.

VY-AADC01 Single Dose

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with idiopathic PD.
• Adequate duration of levodopa therapy.
• Disease duration of at least 5 years or more.
• Modified Hoehn \& Yahr Staging with at least 2.5 hours or more in the OFF state.
• Candidate for surgical intervention because of disabling motor complications.
• UPDRS Part III (total score) of at least 25 in the OFF state.
• Unequivocal responsiveness to dopaminergic therapy.
• Stable Parkinson's symptoms and medications for at least 4 weeks prior to screening evaluation.
• Ability to comprehend and sign the informed consent.
• Normal laboratory values prior to surgery.
• Medically and mentally capable of undergoing and complying with the surgical procedure and protocol requirements.
• Ability to travel to study visits alone or able to designate a caregiver.
• Subject agrees to defer any neurological surgery, including deep brain stimulation, until after completing the 12 month study visit (unless recommended by study neurologist).
• Approved by the Eligibility Review Committee.

You may not qualify if:

• Atypical or secondary parkinsonism, including but not limited to symptoms believed to be due to trauma, brain tumor, infection, cerebrovascular disease, other neurological disease, or to drugs, chemicals, or toxins.
• Presence of dementia as defined by a Mattis Dementia Rating Scale - Second Edition (MDRS-2) score of less than 130 at screening.
• Presence or history of psychosis, with the exception of mild, benign hallucinations believed in the judgment of the Investigator to be related to Parkinson's medications.
• Presence of severe depression, as indicated by a BDI-II score greater than 28, or a history of a major affective disorder within 5 years of screening evaluation.
• Active suicidal ideation or suicide attempt within 5 years of screening evaluation.
• History of substance abuse within 2 years of screening evaluation.
• Brain imaging abnormalities in the striatum or other regions that would substantially increase risk of surgery.
• Contraindication to MRI and/or gadoteridol.
• Coagulopathy or inability to temporarily stop any anticoagulation or antiplatelet therapy prior to surgery.
• Prior brain surgery including lesioning procedures, deep brain stimulation, infusion therapies or any other brain surgery.
• Prior gene transfer.
• History of stroke, poorly controlled or significant cardiovascular disease, diabetes, or any other acute or chronic medical condition.
• History of malignancy other than treated carcinoma in situ within 3 years of screening evaluation.
• Clinically apparent or laboratory-detected infection.
• Prior or current treatment with any investigational agent within 2 months of screening evaluation.

Sponsors & Collaborators

• Neurocrine Biosciences: lead
• Voyager Therapeutics: collaborator

Study Sites (4)

University of California, San Francisco (UCSF)

San Francisco, California, 94143, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Ohio State University (OSU)

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Links

• Company Website

MeSH Terms

Conditions

Parkinson Disease; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Nervous System Diseases; Neurodegenerative Diseases; Parkinsonian Disorders

Condition Hierarchy (Ancestors)

Synucleinopathies

Study Officials

• Steve Hersch, MD

  Voyager Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: February 27, 2017
• Study Start: May 11, 2017
• Primary Completion: August 10, 2021
• Study Completion: August 10, 2021
• Last Updated: March 21, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)