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GDNF Gene Therapy for Parkinson's Disease

Primary Purpose

Parkinson's Disease

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AAV2-GDNF
Sponsored by
Brain Neurotherapy Bio, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson's Disease focused on measuring PD, Parkinson's disease, Neurotrophic factor, Growth factor, Glial cell line-derived neurotrophic factor, GDNF, AAV, Gene therapy

Eligibility Criteria

35 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Male and female adults 35-75 years of age (inclusive)
  • Diagnosed with Parkinson's disease
  • Modified Hoehn and Yahr stage I-III OFF medication

  • Time since receiving a clinical diagnosis of PD and disease severity consistent with one of the following:

    1. EITHER: Less than 5 years since clinical diagnosis of PD and mild to moderate UPDRS III OFF score
    2. OR: At least 4 years since clinical diagnosis of PD and moderate to severe UPDRS III OFF score
  • Responsiveness to levodopa

Key Exclusion Criteria:

  • Atypical parkinsonism
  • Severe dyskinesia
  • Presence of dementia, psychosis, substance abuse or qualify as "severe depression"
  • Prior brain surgery (i.e. deep brain stimulator or DBS implantation) or other brain imaging abnormalities
  • Receiving an investigational drug
  • History of cancer or poorly controlled medical conditions that would increase surgical risk
  • Inability to tolerate laying flat in an MRI or allergy to gadolinium

Sites / Locations

  • University of California Irvine
  • University of California San Francisco
  • The Ohio State University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Earlier stage PD

Later stage PD

Arm Description

Outcomes

Primary Outcome Measures

The incidence of Treatment-Emergent Adverse Events (TEAE) assessed clinically by physical and neurological examinations
Evaluation of the safety and tolerability through the assessment of incidence of TEAE, identified by MedDRA preferred term and grouped by MedDRA System Organ Class, as well as clinically meaningful changes in clinical exams or laboratory assays.

Secondary Outcome Measures

Motor symptoms as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
Change from baseline in the MDS-UPDRS. The MDS-UPDRS contains 4 subscales: Part I, non-motor aspects of experiences of daily living (13 items); Part II, motor aspects of experiences of daily living (13 items); Part III, motor examination (33 scores based on 18 items); Part IV, motor complications (6 items). The rating for each item, or sub-item, is from 0 (normal) to 4 (severe). The total score for each Part is obtained from the sum of the corresponding item scores.
Non-motor symptoms of Parkinson's disease as assessed by the Non-Motor Symptom Scale (NMSS)
Change from baseline in the NMSS. The NMSS evaluates 9 domains of non-motor of severity and frequency of PD symptoms associated with cardiovascular health, sleep and fatigue, mood and cognition, perceptual problems and hallucinations, attention and memory, gastrointestinal tract, urinary, sexual function, and a miscellaneous domain for other common non-motor conditions. Severity x frequency scores range 0-108, with 0 being less severe and less frequent.
Brain dopaminergic cell integrity as measured by DaTscan
Percentage and absolute changes in Ioflupane retention as a marker for dopamine transporter protein expressed by dopamine producing cells within the brain. Measured by quantitative analysis of DaTscan SPECT imaging.

Full Information

First Posted
November 7, 2019
Last Updated
January 18, 2023
Sponsor
Brain Neurotherapy Bio, Inc.
Collaborators
Asklepios Biopharmaceutical, Inc., California Institute for Regenerative Medicine (CIRM)
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1. Study Identification

Unique Protocol Identification Number
NCT04167540
Brief Title
GDNF Gene Therapy for Parkinson's Disease
Official Title
Open-Label Safety Study of Glial Cell Line-Derived Neurotrophic Factor Gene Transfer (AAV2- GDNF) in Parkinson's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 1, 2020 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
June 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Brain Neurotherapy Bio, Inc.
Collaborators
Asklepios Biopharmaceutical, Inc., California Institute for Regenerative Medicine (CIRM)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The objective of this Phase 1b investigation is to evaluate the safety and potential clinical effect of AAV2-GDNF delivered to the putamen in subjects with either a recent or a long-standing diagnosis of PD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
PD, Parkinson's disease, Neurotrophic factor, Growth factor, Glial cell line-derived neurotrophic factor, GDNF, AAV, Gene therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
A total of 12 study participants will be administered the investigational product in this Phase 1b trial. Participants will be enrolled into cohorts, based upon the duration and stage of their PD. Six (6) participants will be dosed in each cohort.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Earlier stage PD
Arm Type
Experimental
Arm Title
Later stage PD
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
AAV2-GDNF
Intervention Description
Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose
Primary Outcome Measure Information:
Title
The incidence of Treatment-Emergent Adverse Events (TEAE) assessed clinically by physical and neurological examinations
Description
Evaluation of the safety and tolerability through the assessment of incidence of TEAE, identified by MedDRA preferred term and grouped by MedDRA System Organ Class, as well as clinically meaningful changes in clinical exams or laboratory assays.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Motor symptoms as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
Description
Change from baseline in the MDS-UPDRS. The MDS-UPDRS contains 4 subscales: Part I, non-motor aspects of experiences of daily living (13 items); Part II, motor aspects of experiences of daily living (13 items); Part III, motor examination (33 scores based on 18 items); Part IV, motor complications (6 items). The rating for each item, or sub-item, is from 0 (normal) to 4 (severe). The total score for each Part is obtained from the sum of the corresponding item scores.
Time Frame
18 months
Title
Non-motor symptoms of Parkinson's disease as assessed by the Non-Motor Symptom Scale (NMSS)
Description
Change from baseline in the NMSS. The NMSS evaluates 9 domains of non-motor of severity and frequency of PD symptoms associated with cardiovascular health, sleep and fatigue, mood and cognition, perceptual problems and hallucinations, attention and memory, gastrointestinal tract, urinary, sexual function, and a miscellaneous domain for other common non-motor conditions. Severity x frequency scores range 0-108, with 0 being less severe and less frequent.
Time Frame
18 months
Title
Brain dopaminergic cell integrity as measured by DaTscan
Description
Percentage and absolute changes in Ioflupane retention as a marker for dopamine transporter protein expressed by dopamine producing cells within the brain. Measured by quantitative analysis of DaTscan SPECT imaging.
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Male and female adults 35-75 years of age (inclusive) Diagnosed with Parkinson's disease Modified Hoehn and Yahr stage I-III OFF medication Time since receiving a clinical diagnosis of PD and disease severity consistent with one of the following: EITHER: Less than 5 years since clinical diagnosis of PD and mild to moderate UPDRS III OFF score OR: At least 4 years since clinical diagnosis of PD and moderate to severe UPDRS III OFF score Responsiveness to levodopa Key Exclusion Criteria: Atypical parkinsonism Severe dyskinesia Presence of dementia, psychosis, substance abuse or qualify as "severe depression" Prior brain surgery (i.e. deep brain stimulator or DBS implantation) or other brain imaging abnormalities Receiving an investigational drug History of cancer or poorly controlled medical conditions that would increase surgical risk Inability to tolerate laying flat in an MRI or allergy to gadolinium
Facility Information:
Facility Name
University of California Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94103
Country
United States
Facility Name
The Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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GDNF Gene Therapy for Parkinson's Disease

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