Parkinson's Disease
Conditions
Keywords
PD, Parkinson's disease, Neurotrophic factor, Growth factor, Glial cell line-derived neurotrophic factor, GDNF, AAV, Gene therapy
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.
Interventions
BIOLOGICALAAV2-GDNF
Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose
Sponsors
AskBio Inc
California Institute for Regenerative Medicine (CIRM)
Brain Neurotherapy Bio, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed