ZR001 Chemogenetics Gene Therapy Study in Patients With Parkinson's Disease
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age40-70
SponsorQianfoshan Hospital
About this trial
This study aims to evaluate the safety, tolerability, and preliminary efficacy of ZR001, a novel chemogenetic gene therapy product, in patients with moderately advanced Parkinson's disease (PD). ZR001 is administered via stereotactic injection into the bilateral substantia nigra, followed by postoperative ultra-low-dose clozapine to activate the transduced direct pathway, with the goal of improving motor symptoms of Parkinson's disease.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥40 and ≤70 years (at the time of signing the informed consent), any gender.
Diagnosed with Parkinson's disease according to the Diagnostic Criteria for Parkinson's Disease in China (2016 edition).
Modified Hoehn & Yahr stage between 2.5 and 4.
History of Parkinson's disease for at least 5 years but less than 15 years.
Disqualifiers
Have participated in or are currently participating in other clinical studies of PD drugs or other AAV gene therapy or cell therapy.
Presence of other severe psychiatric disorders (e.g., severe depression, schizophrenia, etc.).
Previous adverse reactions to clozapine, such as agranulocytosis or severe neutropenia.
Participants with known allergic constitution, including allergy or hypersensitivity to clozapine, prednisone acetate, other glucocorticoids, their excipients, or local anesthetics.
Trial design
Design model
Single group
Treatments tested in this trial
ZR001
GeneticThis is a prospective, open-label, single-arm, single-dose, dose-escalation, investigator-initiated trial. A sentinel-based 3+ design will evaluate three dose cohorts: 0.5E12, 1.0E12, and 2.0E12 vg/participant. One sentinel participant is enrolled per cohort; a Safety Review Committee assesses safety at 6-8 weeks post-injection before escalation. After completing escalation, remaining participants are enrolled at the selected dose for expansion. Total planned enrollment is 6-8 evaluable participants.
Treatment groups
8 Participants
are divided into 1 treatment groupGroup A: ZR001 groupExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
The incidence of adverse events and serious adverse events after ZR001 treatment
Adverse events and serious adverse events will be collected from dosing through Week 52; Including vital signs, clinical laboratory parameters, and physical examinations
Time frame
52 weeksSecondary outcomes
1
The differences of the daily levodopa equivalent dose (LED) after ZR001 treatment
Compare total daily LED (collected from dosing through Week 52) with baseline; LED is calculated using standard conversion factors for all dopaminergic medications
Time frame
52 weeks2
The differences of the Clinical Global Impression - Severity (CGI-S) after ZR001 treatment
Compare the change in CGI-S scores from baseline to post-treatment; CGI-S is a 7-point-scale (1 = normal to 7 = among the most extremely ill)
Time frame
52 weeks3
The differences of the Clinical Global Impression - Improvement (CGI-I) after ZR001 treatment
Compare the change in CGI-I scores from baseline to post-treatment; CGI-I is a 7-point-scale (1 = very much improved to 7 = very much worse)
Time frame
52 weeks4
The differences of the MDS Unified Parkinson's Disease Rating Scale (MDS-UPDRS) after ZR001 treatment
Change from baseline in the total UPDRS score and subscores for Parts I-IV. The UPDRS is an internationally recognized rating scale for Parkinson's disease symptoms. It comprises 4 parts assessing non-motor and motor experiences of daily living and motor complications. The total score is the sum of all 4 part scores, ranging from 0 to 183 (Part I: 0-16, Part II: 0-52, Part III: 0-56, Part IV: 0-23), with higher scores indicating greater severity of Parkinson's disease symptoms. Part I assesses non-motor experiences of daily living, including neuropsychiatric symptoms such as cognition, mood, and behavior. Part II assesses motor experiences of daily living, including activities such as writing, dressing, personal hygiene, and turning in bed. Part III assesses motor function through clinician-scored examination, including facial expression, tremor, rigidity, bradykinesia, postural instability, and gait. Part IV assesses motor complications, including dyskinesia and motor fluctuations.
Time frame
52 weeksOther outcomes
1
The differences of the brain MRI performance after ZR001 treatment
Change from baseline to Week 52 in MRI parameters
Time frame
52 weeks2
The differences of the electromyography (EMG) tremor analysis after ZR001 treatment
Change from baseline to Week 52 in EMG tremor analysis
Time frame
52 weeks3
The differences of the orthostatic blood pressure regulation after ZR001 treatment
Change from baseline in orthostatic blood pressure response (systolic and diastolic) measured during supine to standing test
Time frame
52 weeks4
The differences of the polysomnography (PSG) parameters after ZR001 treatment
Change from baseline in polysomnography (PSG) parameters
Time frame
52 weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
Qianfoshan Hospital
Lead sponsor
Shenzhen Loongen Biotechnology Co., Ltd.
Collaborator
Source ClinicalTrials.gov
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