GDNF Gene Therapy for Parkinson's Disease

• ClinicalTrials.gov Identifier: NCT04167540
• Recruitment Status: Active, not recruiting
• First Posted: November 19, 2019
• Last Update Posted: January 19, 2023
• Sponsor: Brain Neurotherapy Bio, Inc.
• Collaborators: Asklepios Biopharmaceutical, Inc.; California Institute for Regenerative Medicine (CIRM)
• Information provided by (Responsible Party): Brain Neurotherapy Bio, Inc.

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 (Clinical Trial)
• Actual Enrollment: 11 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.
• 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: April 1, 2020
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: June 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

Outcome Measures

Primary Outcome Measures :

1. The incidence of Treatment-Emergent Adverse Events (TEAE) assessed clinically by physical and neurological examinations [ Time Frame: 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 :

1. Motor symptoms as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) [ Time Frame: 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.
2. Non-motor symptoms of Parkinson's disease as assessed by the Non-Motor Symptom Scale (NMSS) [ Time Frame: 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.
3. Brain dopaminergic cell integrity as measured by DaTscan [ Time Frame: 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

• Ages Eligible for Study: 35 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

  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

Contacts and Locations

Locations

United States, California

University of California Irvine

Irvine, California, United States, 92697

University of California San Francisco

San Francisco, California, United States, 94103

United States, Ohio

The Ohio State University Medical Center

Columbus, Ohio, United States, 43210

Sponsors and Collaborators

Brain Neurotherapy Bio, Inc.

Asklepios Biopharmaceutical, Inc.

California Institute for Regenerative Medicine (CIRM)

More Information

• Responsible Party: Brain Neurotherapy Bio, Inc.
• ClinicalTrials.gov Identifier: NCT04167540
• Other Study ID Numbers: GDNF-102
• First Posted: November 19, 2019
• Last Update Posted: January 19, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Brain Neurotherapy Bio, Inc.:

PD; Parkinson's disease; Neurotrophic factor; Growth factor; Glial cell line-derived neurotrophic factor; GDNF; AAV; Gene therapy

Additional relevant MeSH terms:

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