A Study on the Safety, Tolerability, and Efficacy of PDR-001 Injection for Bilateral Stereotactic Subthalamic Nucleus (STN) Clearance of α-synuclein
Phase: PHASE1
Conditions: Parkinson Disease (PD)
Sponsor: Ruijin Hospital

 
A Prospective Study on the Safety, 
Tolerability, and Efficacy of PDR-001 
Injection for Bilateral Stereotactic 
Subthalamic Nucleus (STN) Clearance of 
Alpha-Synuclein 
 
 
 
July 6, 2025 
 
 
 

NIH Clinical Protocol Template: PDR-001 Study 
 
1. STUDY OVERVIEW 
 
**Full Protocol Title:**   
A Prospective Study on the Safety, Tolerability, and Efficacy of PDR-001 Injection for 
Bilateral Stereotactic Subthalamic Nucleus (STN) Clearance of Alpha-Synuclein 
 
**Protocol ID Number:** NA   
**Version Number and Date:** V1.0, July 6, 2025   
**Principal Investigator:** Jun Liu   
**Institution:** Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University 
School of Medicine   
**Study Period:** May 2025 to December 2029   
**Study Phase:** Phase I/II (Exploratory) 
 
**Study Sites:** Single-site trial at Ruijin Hospital, Shanghai 
 
2. OBJECTIVES AND ENDPOINTS 
 
2.1 Primary Objective (52-week Core Phase): 
Evaluate the safety and tolerability of PDR-001 injected bilaterally into the STN of patients 
with early primary PD. 
 
2.2 Secondary Objective: 
Evaluate the clinical efficacy of PDR-001 within 52 weeks post-injection. 
 
2.3 Long-term Objective: 
Evaluate long-term safety and efficacy from week 52 up to 5 years. 

 
2.4 Endpoints 
Primary Endpoints: 
- Incidence of adverse events (AEs) and serious adverse events (SAEs) 
- Change in rAAV neutralizing and binding antibody titers 
- Change in whole blood rAAV vector titers 
 
Secondary Endpoints: 
- Change in daily Levodopa dose or Levodopa Equivalent Dose (LED) 
- Change from baseline in the following scales: 
  - MDS-UPDRS I-IV 
  - PGI-I, CGI-I 
  - MMSE, HAMD, HAMA 
  - PDSS-2, PDQ-39 
  - MoCA, NMSQ, SCOPA-AUT, RBDSQ, SS-16, PSQI, Wexner, Berg, Tinetti, Webster, GFQ 
 
Long-term Endpoints (52 weeks – 5 years): 
- All primary and secondary endpoints continued over time 
- [18F]F-dopa PET gene expression 
- DaT-SPECT putaminal binding ratio changes 
 
3. BACKGROUND AND RATIONALE 
 
3.1 Disease Background 
Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by the death 
of dopaminergic neurons in the substantia nigra. Motor and non-motor symptoms impair 

quality of life. In China, PD prevalence ranges from 16.7 to 440.3 per 100,000, affecting 
1.7% of the elderly population. 
 
3.2 Unmet Medical Need 
Current treatments offer symptomatic relief but do not halt disease progression. Alpha-
synuclein aggregation is a hallmark of PD pathology. There is a need for innovative 
therapies that directly target and degrade alpha-synuclein. 
 
3.3 Study Agent (PDR-001) 
PDR-001 is a novel gene therapy delivered via AAV9 vector encoding a tripeptide (Tat-βsyn-
deg) designed to degrade α-synuclein. 
 
3.4 Preclinical Data 
- **Mice (A53T model):** Significant reduction in α-syn, increased dopaminergic neurons, 
improved behavior 
- **Non-human primates:** Improved motor scores, PET signal in striatum, no systemic 
toxicity 
 
3.5 Rationale for Study Design 
First-in-human trial assessing safety and potential clinical benefit of PDR-001 in early-stage 
PD. Bilateral STN chosen for direct delivery. 
 
3.6 Risk/Benefit Assessment 
**Risks:** Neurosurgical injection, immune response to AAV, transient neuropsychiatric 
symptoms   
**Benefits:** Potential disease-modifying effect by reducing toxic α-synuclein burden   
**Conclusion:** Favorable risk-benefit ratio supports study initiation 
 
4. STUDY DESIGN AND METHODS 
 

4.1 Overall Design 
Single-arm, open-label, single-center trial. Total enrollment of 12 participants. Dose-
escalation (n=6 in 2 dose levels), followed by an expansion cohort (n=6). 
 
4.2 Study Duration 
- 52-week core study 
- Up to 5-year long-term follow-up 
 
4.3 Sample Size Justification 
Exploratory study with 12 patients. No formal power calculation. Safety and biological 
signals will guide future studies. 
 
4.4 Study Intervention 
- **Drug:** PDR-001 injection (AAV9 vector expressing Tat-βsyn-deg) 
- **Route:** Bilateral stereotactic injection into the STN 
- **Method:** Stereotactic multi-point microinjection (4 targets total) 
 
4.5 Study Population 
12 patients with early-stage primary PD. 
 
Inclusion Criteria (summary): 
- Age 40–65, Hoehn-Yahr ≤ 2, disease duration ≤ 5 years 
- Adequate cognitive and liver/renal function 
- Negative for HIV, HBV, HCV 
 
Exclusion Criteria (summary): 
- Atypical or secondary Parkinsonism 
- History of brain surgery, malignancy, or severe comorbidities 

- Pregnancy or nursing 
 
5. STUDY PROCEDURES AND ASSESSMENTS 
 
Participants will undergo the following evaluations: 
 
- **Preoperative screening:** Informed consent, demographics, physical exam, imaging, lab 
tests (hematology, biochemistry, serology, pregnancy test), ECG, PD assessments 
- **Intervention:** Stereotactic bilateral STN injection of PDR-001 under general anesthesia 
- **Follow-up:** At week 4, 12, 26, 39, and 52 post-injection, and every 26 weeks during 
long-term follow-up. Evaluations include lab tests, imaging (MRI, PET, DaT-SPECT), PD 
scales, safety assessments 
 
6. SAFETY MONITORING AND ADVERSE EVENT REPORTING 
 
- All AEs and SAEs will be recorded from consent through 52-week core study and 
throughout long-term follow-up if related to gene therapy. 
- SAEs will be reported to the sponsor and Ethics Committee within 24 hours. 
- Safety will be reviewed by an independent Safety Review Committee (SRC). 
 
7. STATISTICAL ANALYSIS PLAN 
 
- **Descriptive statistics** will summarize safety, tolerability, and efficacy outcomes. 
- Categorical data: frequencies and percentages 
- Continuous data: mean, median, standard deviation, range 
- No formal hypothesis testing due to exploratory nature 
 
8. ETHICAL CONSIDERATIONS 
 

- The study will comply with the Declaration of Helsinki and GCP guidelines. 
- Ethics Committee approval is required before initiation. 
- Informed consent will be obtained from all participants. 
 
9. DATA HANDLING AND RECORD RETENTION 
 
- Electronic Data Capture (EDC) system will be used for data collection. 
- All source documents and CRFs will be retained for a minimum of 5 years after study 
completion. 
- Patient confidentiality will be protected through anonymization and restricted access. 
 
10. REFERENCES 
 
(Full reference list available upon request, based on Chinese and international preclinical 
and clinical gene therapy literature, supporting PDR-001 development.)