PD
Conditions
Keywords
PD, gene therapy, Adeno-Associated Virus
Brief summary
The purpose of the study is to evaluate the safety and tolerability of BBM-P002 for stereotactic injection to treat participants with idiopathic Parkinson's Disease (PD) during the dose-limiting toxicity (DLT) observation period.
Detailed description
This is a single-arm, open-label study to evaluate the safety, tolerability, efficacy, pharmacokinetic, pharmacodynamic, and immune response of BBM-P002 within 52 weeks after into the bilateral putamen in Parkinson's disease, as well as the long-term safety and efficacy of BBM-P002 for up to 5 years post injection. BBM-P002 is an AAV-based gene therapy that delivers a therapeutic gene cassette into putamen for the treatment of Parkinson's Disease.
Interventions
GENETICInjecting BBM-P002 into the bilateral putamen
BBM-P002 is an AAV-based gene therapy that delivers a therapeutic gene cassette into putamen for the treatment of Parkinson's Disease
Sponsors
Shanghai Xinzhi BioMed Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Participants with a diagnosis of Parkinson's disease for ≥ 5 years. 2. The Hoehn-Yahr staging meets the requirements during the OFF periods. 3. The MDS-UPDRS Part III score met the requirements during the OFF periods. the levodopa challenge test was positive 4. During the screening period, participants were required to take the same stable dose of dopamine-releasing drugs (such as levodopa) regularly 5. The participants agreed to postpone the neurosurgical procedures related to the indication treatment during the main study phase 6. The participants agreed not to participate in any other therapeutic intervention studies during the trial period 7. The participants agreed not to receive the vaccine during the main study phase 8. From the screening period until at least 52 weeks after dosing, use a reliable contraceptive method 9. The participants had good compliance and were able to undergo regular follow-ups. During the follow-up period, they were able to accurately complete the diary cards. Family members, guardians or caregivers could assist the subjects in filling out the diary cards 10. Voluntarilyvoluntarily participated in the study and signed the informed consent form
Exclusion criteria
1. Atypical or secondary Parkinsonism 2. Have contraindications for surgery or have previously undergone brain surgery 3. The participants has an abnormal brain MRI suggestive of brain pathology other than Parkinson's disease 4. Those with severe cognitive impairments 5. Those with severe depression or severe anxiety 6. Abnormal liver function 7. Abnormal coagulation function 8. Abnormalities in infectious disease screening 9. Currently undergoing antiviral treatment for hepatitis 10. Suffering from unstable or severe diseases in the cardiovascular, respiratory, digestive, nervous, hematological, immune and other systems 11. Suffering from malignant tumors or having a history of tumors 12. Previous history of severe allergies 13. Exclude those who have participated in other clinical trials within the past three months 14. Had received gene therapy during the screening period 15. Select those who have received stem cell treatment within the past 12 months 16. Exclude those who have used other investigational drugs within the past 4 weeks 17. During the screening period, if the individual had received live vaccines within the previous 2 months, or had a history of vaccination within the last 30 days, they would be excluded. 18. Having a history of alcohol dependence or drug addiction 19. Pregnant or lactating female participants 20. The situations that were determined by the investigator to be unsuitable for inclusion in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicity (DLT) events | Within 4 weeks | To evaluate the rate of incidence of DLT events determined by the Safety Data Review Committee (SRC) in DLT observation period after injecting BBM-P002 |
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Within 4 weeks | To evaluate the safety of BBM-P002 by AEs and SAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Within 5 years | To assess the long-term safety of BBM-P002 by AEs and SAEs |
| Changes in the titers of neutralizing antibodies and binding antibodies in the recombinant adenovirus capsid of blood | Within 5 years | To assess changes in the titers of neutralizing antibodies and binding antibodies in the recombinant adenovirus capsid of blood after injecting BBM-P002 |
| Changes in the results of the cranial MRI scan | Within 5 years | To assess changes in the results of the cranial MRI scan after injecting BBM-P002 |
| Changes from baseline in MDS - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I/II/III/IV scores | Within 5 years | The theoretical maximum total score of the MDS-UPDRS is 272 points. It comprehensively assesses the health status of Parkinson's disease patients by evaluating four major aspects: non-motor symptoms, daily activities, motor function, and motor complications. The higher the score, the more severe the condition |
| Changes from baseline in the Patient Global Impression of Improvement (PGI-I) scores | Within 5 years | Choose a number from 1 to 7. The higher the number choosen, the worse the improvement. |
| Changes from baseline in the Clinical Global Impression of Improvement (CGI-I) scores | Within 5 years | Choose a number from 1 to 7. The higher the number choosen, the worse the improvement. |
| Changes in the activity levels of gene expression products under18F-dopa PET scanning from baseline [striatum - occipital lobe average radioactivity count ratio] | Within 5 years | To assess changes in the activity levels of gene expression products under18F-dopa PET scanning from baseline \[striatum - occipital lobe average radioactivity count ratio\] after injecting BBM-P002 |
| Changes from baseline in daily levodopa dose or equivalent dose of levodopa | Within 5 years | To assess changes from baseline in the levodopa dosage or levodopa equivalent dosage after injecting BBM-P002 |
| Changes from baseline in the percentage at on time. | Within 5 years | To assess changes from baseline in the percentage at on time after injecting BBM-P002 |
Countries
China
Contacts
CONTACTWenshu Luo, Ph.D
PRINCIPAL_INVESTIGATORJun Liu, MD
Ruijin Hospital
PRINCIPAL_INVESTIGATORJing Sun, MD
Ruijin Hospital
Outcome results
None listed