GDNF Gene Therapy for Parkinson's Disease

Sponsor

Brain Neurotherapy Bio, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04167540

Collaborator

Asklepios Biopharmaceutical, Inc. (Industry), California Institute for Regenerative Medicine (CIRM) (Other)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Biological: AAV2-GDNF	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

Open-Label Safety Study of Glial Cell Line-Derived Neurotrophic Factor Gene Transfer (AAV2- GDNF) in Parkinson's Disease

Actual Study Start Date :

Apr 1, 2020

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Earlier stage PD	Biological: AAV2-GDNF Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose
Experimental: Later stage PD	Biological: AAV2-GDNF Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose

Arm

Intervention/Treatment

Experimental: Earlier stage PD

Biological: AAV2-GDNF

Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose

Experimental: Later stage PD

Biological: AAV2-GDNF

Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose

Outcome Measures

Primary Outcome Measures

The incidence of Treatment-Emergent Adverse Events (TEAE) assessed clinically by physical and neurological examinations [5 years]
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) [18 months]
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) [18 months]
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 [18 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Irvine	Irvine	California	United States	92697
2	University of California San Francisco	San Francisco	California	United States	94103
3	The Ohio State University Medical Center	Columbus	Ohio	United States	43210