ZR001 Chemogenetics Gene Therapy Study in Patients With Parkinson's Disease

NCT07718659 | Not Yet Recruiting Phase 1 DMC

• 2 other identifiers: ZR001-101YXLL-KY-2026 (101)
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson's Disease (PD); Parkinsonian Disorders

Keywords

AAV; DREADD; PD; D1-MSN; Gene Therapy; Chemogenetics; Parkinson's Disease; Clozapine; Central Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases

Outcome Measures

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

  52 weeks

Secondary Outcomes (14)

• The differences of the daily levodopa equivalent dose (LED) after ZR001 treatment

  52 weeks

• The differences of the Clinical Global Impression - Severity (CGI-S) after ZR001 treatment

  52 weeks

• The differences of the Clinical Global Impression - Improvement (CGI-I) after ZR001 treatment

  52 weeks

• The differences of the MDS Unified Parkinson's Disease Rating Scale (MDS-UPDRS) after ZR001 treatment

  52 weeks

• The differences of the Parkinson's Disease Questionnaire 39 (PDQ-39) after ZR001 treatment

  52 weeks

Other Outcomes (4)

• The differences of the brain MRI performance after ZR001 treatment

  52 weeks

• The differences of the electromyography (EMG) tremor analysis after ZR001 treatment

  52 weeks

• The differences of the orthostatic blood pressure regulation after ZR001 treatment

  52 weeks

Study Arms (1)

ZR001 group

EXPERIMENTAL

The study will enroll up to 3 cohorts: low-dose, medium-dose, and high-dose ZR001 administration.

Genetic: ZR001

Interventions

ZR001 GENETIC

This 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.

ZR001 group

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who meet all of the following criteria are eligible for enrollment:
• 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.
• Moderate to severe MDS-UPDRS Part III score in the off period, and improvement rate ≥30% after acute levodopa stress test.
• Clinically stable symptoms and stable types and doses of anti-Parkinsonian medications within 3 months prior to enrollment.
• Agree to provide biological samples required for the study (e.g., blood, urine).
• Consent to hospitalization for intraparenchymal drug injection surgery.
• Male or female participants of childbearing potential agree to use effective contraceptive methods (oral contraceptives are prohibited) from the time of signing the informed consent until at least 6 months after discontinuing clozapine.
• Participants or their stable caregivers are able to understand and willing to comply with the study requirements and procedures, voluntarily participate, and sign the informed consent. If a caregiver is present, they must accompany the participant to study visits and assist the investigator in completing relevant scale assessments.

You may not qualify if:

• Participants who meet any of the following criteria will be excluded from this study:
• 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.
• History of alcohol or drug abuse within the past 2 years.
• Participants requiring invasive or non-invasive ventilatory support.
• Serum AAV binding antibody titer \>1:2000.
• Presence of clinically significant laboratory abnormalities as assessed by the investigator: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin; creatinine, hemoglobin (Hb), prothrombin time (PT), activated partial thromboplastin time (APTT), fasting blood glucose, platelets (PLT).
• Presence of liver disease, heart disease, kidney disease or history thereof, which, in the investigator's assessment, may pose surgical or drug-related risks to the participant.
• Suffering from autoimmune diseases or immunocompromised status requiring hormone or immunosuppressive therapy, which, in the investigator's assessment, may pose surgical or drug-related risks.
• Suffering from other severe systemic diseases (e.g., cor pulmonale, moderate-to-severe asthma, etc.) that, in the investigator's assessment, may pose surgical or drug-related risks.
• In the investigator's assessment, the participant has contraindications to anesthesia or surgery and is unsuitable for intraparenchymal administration, or other special circumstances.
• Positive for human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis C antibody, syphilis antibody, active TORCH virus infection, or active Epstein-Barr virus infection.
• Concomitant use of any of the following medications within 90 days prior to administration, or planned immunosuppressive therapy (cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab) within 6 months after start of the trial, except for prophylactic medications specified in the protocol.

Sponsors & Collaborators

• Qianfoshan Hospital: lead
• Shenzhen Loongen Biotechnology Co., Ltd.: collaborator

Study Sites (1)

The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital)

Jinan, Shandong, China

Location

MeSH Terms

Conditions

Parkinson Disease; Parkinsonian Disorders; Central Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Nervous System Diseases; Synucleinopathies

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician

Model Details: Single Group Assignment: An Open-label, Single Arm, Dose-Escalation Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of ZR001 administration.

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 22, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)