Safety and Efficacy Study of Parkinson's Disease Gene Therapy Drug (BBM-P002)

A Single-Arm, Open-Label, Exploratory Clinical Study of BBM-P002 Gene Therapy for Parkinson's Disease

Safety and Efficacy Study of BBM-P002 in participants with primary advanced Parkinson's disease

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: BBM-P002

Detailed Description

Parkinson's disease is a neurodegenerative disorder involving loss of dopaminergic neurons in the substantia nigra. This study is a single-center, single-arm, open-label, treatment clinical study to evaluate the safety, tolerability and efficacy of an adeno-associated virus (AAV)-based gene therapy, termed BBM-P002, will be injected into the brain via a neurosurgical procedure.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Clinically confirmed diagnosis of idiopathic Parkinson's Disease (PD) in accordance with the 2015 Movement Disorder Society (MDS) diagnostic criteria.
2. Participants aged between 40 and 65 years, inclusive, of any gender.
3. A disease history of five years or more.
4. A Hoehn and Yahr (H-Y) stage of 2.5 to 4 in the Of-state.
5. An adeno-associated virus (AAV) neutralizing antibody titer of fit thecriteria.
6. A Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score greater than 35 in the Off-state, with an improvement of at least 30% following an acute levodopa challenge test.
7. Stable anti-Parkinsonian medication regimen prior to the screening period for at least four weeks.
8. The subject must agree to postpone any other neurosurgical procedures (including deep brain stimulation) during the main study phase, with the exception of emergency neurosurgery for life-threatening conditions.
9. The subject must agree not to participate in other therapeutic interventional studies during the main study phase.
10. The subject must agree not to undergo vaccination during the main study phase.
11. Commitment to using a reliable method of contraception from the screening period until at least 52 weeks post-infusion.
12. The subject must be compliant and capable of attending regular follow-up appointments. The subject must be able to accurately complete a PD patient diary during the follow-up period, with assistance from family members, guardians, or caregivers permitted.
13. The subject must be fully informed about the nature, objectives, procedures, and potential adverse effects of the clinical trial, and must voluntarily consent to participate by signing the informed consent form. In cases where the subject is unable to read, a legally authorized representative or an impartial witness may read the informed consent form and other written materials to them and witness the consent process.

Exclusion Criteria:

1. Diagnosis of atypical or secondary parkinsonian syndromes (e.g., Parkinson-plus syndromes, hereditary parkinsonian syndromes, drug-induced parkinsonism).
2. Presence of surgical contraindications, a history of prior brain surgery such as deep brain stimulation (DBS), pallidotomy, or extrapyramidal surgery, or any other neurosurgical procedure that the investigator deems would interfere with participation in this trial.
3. Previous cranial imaging showing structural brain abnormalities, cerebrovascular malformations, intracranial tumors, risk of intracranial hemorrhage, traumatic brain injury, or other significant anomalies.
4. A Mini-Mental State Examination (MMSE) score of <24.
5. A Patient Health Questionnaire-9 (PHQ-9) score of ≥16.
6. Abnormal liver or kidney function, defined as: Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN), or serum creatinine (Cr) >1.5 times the ULN.
7. Coagulation dysfunction or current use of anticoagulant agents.
8. Positive screening for infectious diseases: positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B virus DNA (HBV-DNA), positive for Hepatitis C virus RNA (HCV-RNA), positive for Human Immunodeficiency Virus (HIV), or seropositive for syphilis.
9. Currently undergoing antiviral treatment for Hepatitis B or C.
10. Presence of unstable or severe concomitant systemic diseases, including but not limited to active tuberculosis, or diseases of the cardiovascular, respiratory, digestive, urinary, neuropsychiatric (e.g., epilepsy), hematologic, or immune systems, or abnormal laboratory values that, in the judgment of the investigator, would make the subject unsuitable for the trial.
11. Current or prior history of a malignant tumor.
12. History of a severe allergic reaction, allergy to contrast agents, or inability to tolerate surgical anesthesia.
13. Current participation in another clinical trial, or participation in any other clinical trial within 3 months prior to the screening period.
14. Prior history of gene therapy before screening.
15. Receipt of stem cell therapy within 6 months prior to the screening period.
16. Use of other investigational drugs within 4 weeks prior to screening or within 5 half-lives of the drug (whichever is longer), or any medication judged by the investigator to interfere with the trial.
17. Receipt of a live vaccine within 2 months prior to the screening period, or any vaccination within 30 days prior to the screening period.
18. History of alcohol dependence or drug addiction, with an inability to adhere to medical advice to abstain from alcohol during the trial period.
19. Female subjectsparticipants who are pregnant or lactating.
20. Any subject deemed unsuitable for enrollment based on the investigator's assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm of BBM-P002; single-arm	Drug: BBM-P002; Genetic: single- dose intracranial injection of BBM-P002 Neurosurgical delivery of BBM-P002 to the brain; Other Names: BBM003

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events and Serious Adverse Events	Safety and Tolerability of BBM-P002 assessed by Adverse Events and Serious Adverse Event	Day 1 through week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of BBM-P002	Changes in gene expression product activity levels assessed by brain ¹⁸F-FDOPA PET	Change from Baseline to week 4，week 52
Efficacy of BBM-P002	Changes in daily oral Levodopa (L-DOPA) dose or Levodopa Equivalent Dose (LEDD);	Change from Baseline to Week 52
Efficacy of BBM-P002	Changes in motor/no motor MDS-Unified Parkinson's Disease Rating Scale-Part III （UPDRS III) The UPDRS III score assesses motor symptoms of Parkinson's disease. The total score ranges from 0 to 132 points, with each of the 33 scoring points rated on a 5-point scale from 0 to 4. A score of 0 indicates normal, with no abnormalities. A score of 1 indicates mild, where symptoms are present but usually do not affect function. A score of 2 indicates mild, where symptoms are mild and have a minor impact on function. A score of 3 indicates moderate, where symptoms are moderate and have a significant impact on function. A score of 4 indicates severe, where symptoms are severe and lead to loss of function. The higher the score, the more severe the motor symptoms.	Change from Baseline to Week 52
Efficacy of BBM-P002	sleep disturbances were characterized using the Parkinson's Disease Sleep Scale-2 (PDSS-2) The PASS scale is a self-rating scale widely used internationally and specifically designed for patients with Parkinson's disease. It is used to systematically assess the occurrence frequency and severity of various sleep disorders in patients. There are a total of 15 items, each with a score range of 0 to 4 points, and a 5-level scoring method is adopted: 0 points: very mild/never (symptoms never occur or are very mild and do not cause disturbance) 1 point: Mild (symptoms occur occasionally and cause slight disturbance) · 2 points Moderate (symptoms occur frequently, moderate distress) · 3 points: Severe (symptoms occur frequently, severe distress) · 4 points: very severe/always (symptoms occur all the time or extremely severe). The score range is from 0 to 60 points. The higher the score, the more severe the sleep disorder.	Change from Baseline to Week 52

Collaborators and Investigators

• Sponsor: Xiangya Hospital of Central South University
• Investigators: Principal Investigator: Lu Shen, M.D, Ph.D, Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2023
• Primary Completion (Actual): October 30, 2025
• Study Completion (Actual): October 30, 2025

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: April 9, 2023
• First Posted (Actual): April 21, 2023

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Gene therapy; Adeno-Associated Virus
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: BBM003- IIT1003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No