Parkinson disease
Conditions
Interventions
High-dose group:Stereotactic Infusion Into Bilateral Putamen of BBM-P002
Low-dose group:Stereotactic Infusion Into Bilateral Putamen of BBM-P002
Sponsors
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Eligibility
Sex/Gender
All
Age
40 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Clinically diagnosed as idiopathic Parkinsons Disease according to the Diagnostic Criteria for Parkinsons Disease in China released in 2016 or in line with the diagnostic criteria for primary PD of the International Parkinson and Movement Disorders Association MDS in 2015; 2 . the age of subjects should be whitin 40-65 years old (including boundary values), male or female; 3. Medical history >=5 years; 4 .The patients are at stage 2.5-4 of the Hoehn and Yahr Scale when they are at the off stage of Parkinson's disease; 5. The titer of the neutralizing antibody of AAV is 35, and the improvement rate of acute levodopa stress test >=30%; 7. Take dopaminergic drugs regularly before the screening period, including levodopa for at least 4 weeks; 8. Subjects agree to postpone other neurosurgery procedures during the main study phase (including deep brain stimulation, except neurosurgery for life-threatening emergencies during the study); 9. Subjects agree not to participate in other therapeutic intervention studies during the main study phase; 10. Subjects agree not to be vaccinated during the main study phase; 11. Use a reliable contraceptive method until at least 52 weeks after the infusion of the drug; 12. Subjects have good compliance and can be followed up regularly. During the follow-up, PD patient diaries can be accurately completed. Family members, guardians or caregivers can help subjects fill out patient diaries; 13. Subjects fully understand the nature, purpose, method and possible adverse reactions of this clinical trial, voluntarily participate in the project, and sign informed consent; If the subject is unable to read, the informed consent and other written materials can be read by a legal representative or an impartial witness so that informed consent can be witnessed.
Exclusion criteria
Exclusion criteria: 1. Atypical or secondary Parkinsons disease syndromes such as Parkinsons disease superimposed syndrome hereditary Parkinsons disease syndrome drug-induced Parkinsons disease syndrome etc; 2. Have contraindications to surgery, or have previously received deep brain stimulation surgery, pallidectomy, extrapyramidal surgery and other brain surgeries, or have received other neurosurgical procedures that the researchers determined would affect their participation in this study; 3. Previous head imaging showed abnormalities in brain structure, cerebrovascular malformations, intracranial tumors, intracranial hemorrhage risk, and brain trauma 4. Mental State Examination Scale (MMSE) score =16; 6.Abnormal liver and kidney function: Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 1.5 times the upper limit of normal value, serum creatinine (Cr) > 1.5 times the upper limit of normal value; 7.Abnormal coagulation function or in the use of anticoagulants; 8.Screening for infectious diseases: Hepatitis B surface antigen (HBsAg) or Hepatitis B virus DNA, HBV-DNA, Hepatitis C virus RNA (HCV-RNA), Human immunodeficiency virus (HIV) or syphilis seropositive; 9.are now receiving hepatitis B, hepatitis C antiviral treatment; 10. Patients with unstable or serious other systemic diseases, including active tuberculosis, cardiovascular system, respiratory system, digestive system, urinary system, psychoneurotic system (such as epilepsy), blood system, immune system and other diseases, or abnormal laboratory test values, the investigator determines that they are not suitable for participation in this study; 11. Have malignant tumors or have a history of malignant tumors; 12. had severe allergic reaction, allergy to contrast agents, or inability to undergo surgical anesthesia; 13. is participating in another clinical trial, or has participated in another clinical trial within 3 months prior to the screening period; 14. Had received gene therapy before screening; 15. Received 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 study drugs (whichever is older), or drugs that the investigator determines affect this trial; 17. Had received live vaccine within 2 months prior to the screening period, or had a history of vaccination within 30 days prior to the screening period; 18. Have a history of alcohol dependence or drug addiction, and cannot stop drinking as prescribed by a doctor during the trial; 19. Pregnant or lactating female subjects; 20. Subjects assessed by the investigator as unsuitable for inclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Detection of whole blood AAV vector (4ml);Adverse events/SAE;Serum recombinant adeno-associated virus rAAV capsid neutralizing antibodies and binding antibodie; | — |
Secondary
| Measure | Time frame |
|---|---|
| MDS-UPDRS I-IV;Clinical Global Impression Scale,CGI-I;Patient Global Impression Scale,PGI-I;Parkinson's Disease Quality of Life Questionnaire,PDQ-39;Parkinson's Disease Sleep Scale 2,PDSS-2;Mini-Mental State Examination,MMSE;Hamilton Anxiety Scale,HAMA;Hamilton Depression Rating Scale,HAMD;Changes in activity levels of gene expression products from baseline via [18F]F-dopa PET;the change of Levodopa Equivalent Dose or the dose of oral Levodopa after surgery; | — |
Countries
China
Contacts
Public ContactLiu Jun
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed