Parkinson's Disease
Conditions
Brief summary
The objective of this clinical trial was to evaluate the safety and tolerability of adeno-associated virus (AAV)-mediated delivery of glutamic acid decarboxylase (GAD) gene transfer into the subthalamic nuclei (STN) of participants with Parkinson's Disease.
Detailed description
The planned length of participation in the study for each participant was approximately 7 months, including a screening period of up to 40 days, randomization, surgery, and a follow-up period of 26 weeks.
Interventions
GENETICAAV-GAD Low Dose
Bilateral infusion of AAV-GAD low dose
GENETICAAV-GAD High Dose
Bilateral infusion of AAV-GAD high dose
PROCEDURESham Surgery
Sham infusion
Sponsors
MeiraGTx, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Participants are enrolled in one of three groups in parallel for the duration of the study.
Eligibility
Sex/Gender
ALL
Age
25 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed Parkinson's Disease * Levodopa responsiveness for at least 12 months * UPDRS Part 3 score of ≥25 points in the off state
Exclusion criteria
* History of brain surgery to treat Parkinson's Disease * Any history of cerebral insult or central nervous system infection * Atypical Parkinson's Disease * Focal or lateralized neurologic deficits * Evidence of significant medical or psychiatric disorders * Cognitive impairment as defined by the Montreal Cognitive Assessment (MoCA) ≤ 20 * Beck Depression Inventory-II score of ≥ 20
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events Related to the Treatment | Baseline to Week 26 | The primary outcome measure is the safety of treatment with AAV-GAD, assessed by the absence of IMP-related treatment-emergent adverse events. |
| Incidence of Serious Adverse Events Related to the Treatment | Baseline to Week 26 | The primary outcome measure is the safety of treatment with AAV-GAD, assessed by the absence of IMP-related serious treatment-emergent adverse events. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 6 medical centers in the United States (US). A total of 14 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| AAV-GAD Low Dose Bilateral infusion of AAV-GAD Low Dose into the STN | 5 |
| AAV-GAD High Dose Bilateral infusion of AAV-GAD High Dose into the STN | 5 |
| Sham Surgery Sham infusion | 4 |
| Total | 14 |
Baseline characteristics
| Characteristic | AAV-GAD Low Dose | AAV-GAD High Dose | Sham Surgery | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 2 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 4 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 4 Participants | 14 Participants |
| Region of Enrollment United States | 5 participants | 5 participants | 4 participants | 14 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 5 / 5 | 5 / 5 | 4 / 4 |
| serious Total, serious adverse events | 2 / 5 | 0 / 5 | 1 / 4 |
Outcome results
Primary
Incidence of Adverse Events Related to the Treatment
The primary outcome measure is the safety of treatment with AAV-GAD, assessed by the absence of IMP-related treatment-emergent adverse events.
Time frame: Baseline to Week 26
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AAV-GAD Low Dose | Incidence of Adverse Events Related to the Treatment | 0 Participants |
| AAV-GAD High Dose | Incidence of Adverse Events Related to the Treatment | 1 Participants |
| Sham Surgery | Incidence of Adverse Events Related to the Treatment | 0 Participants |
Primary
Incidence of Serious Adverse Events Related to the Treatment
The primary outcome measure is the safety of treatment with AAV-GAD, assessed by the absence of IMP-related serious treatment-emergent adverse events.
Time frame: Baseline to Week 26
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AAV-GAD Low Dose | Incidence of Serious Adverse Events Related to the Treatment | 0 Participants |
| AAV-GAD High Dose | Incidence of Serious Adverse Events Related to the Treatment | 0 Participants |
| Sham Surgery | Incidence of Serious Adverse Events Related to the Treatment | 0 Participants |