A Clinical Study to Evaluate the Safety, and Tolerability of BBM-P002 in the Treatment of Parkinson's Disease

Official title

A Single-arm, Open-label, Single-dose Clinical Study to Evaluate the Safety and Tolerability of BBM-P002 for Stereotactic Bilateral Putamen Injection in the Treatment of Idiopathic Parkinson's Disease

Overview

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

• Genetic Injecting 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

Primary outcome measures

• Incidence of dose limiting toxicity (DLT) events [Time frame: Within 4 weeks]
• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Within 4 weeks]

Secondary outcome measures (9)

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Within 5 years]
• Changes in the titers of neutralizing antibodies and binding antibodies in the recombinant adenovirus capsid of blood [Time frame: Within 5 years]
• Changes in the results of the cranial MRI scan [Time frame: Within 5 years]
• Changes from baseline in MDS - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I/II/III/IV scores [Time frame: Within 5 years]
• Changes from baseline in the Patient Global Impression of Improvement (PGI-I) scores [Time frame: Within 5 years]
• Changes from baseline in the Clinical Global Impression of Improvement (CGI-I) scores [Time frame: Within 5 years]
• Changes in the activity levels of gene expression products under18F-dopa PET scanning from baseline [striatum - occipital lobe average radioactivity count ratio] [Time frame: Within 5 years]
• Changes from baseline in daily levodopa dose or equivalent dose of levodopa [Time frame: Within 5 years]
• Changes from baseline in the percentage at on time. [Time frame: Within 5 years]

Eligibility criteria

Inclusion criteria

• Participants with a diagnosis of Parkinson's disease for ≥ 5 years.
• The Hoehn-Yahr staging meets the requirements during the OFF periods.
• The MDS-UPDRS Part III score met the requirements during the OFF periods. the levodopa challenge test was positive
• During the screening period, participants were required to take the same stable dose of dopamine-releasing drugs (such as levodopa) regularly
• The participants agreed to postpone the neurosurgical procedures related to the indication treatment during the main study phase
• The participants agreed not to participate in any other therapeutic intervention studies during the trial period
• The participants agreed not to receive the vaccine during the main study phase
• From the screening period until at least 52 weeks after dosing, use a reliable contraceptive method
• 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
• Voluntarilyvoluntarily participated in the study and signed the informed consent form

Exclusion criteria

• Atypical or secondary Parkinsonism
• Have contraindications for surgery or have previously undergone brain surgery
• The participants has an abnormal brain MRI suggestive of brain pathology other than Parkinson's disease
• Those with severe cognitive impairments
• Those with severe depression or severe anxiety
• Abnormal liver function
• Abnormal coagulation function
• Abnormalities in infectious disease screening
• Currently undergoing antiviral treatment for hepatitis
• Suffering from unstable or severe diseases in the cardiovascular, respiratory, digestive, nervous, hematological, immune and other systems
• Suffering from malignant tumors or having a history of tumors
• Previous history of severe allergies
• Exclude those who have participated in other clinical trials within the past three months
• Had received gene therapy during the screening period
• Select those who have received stem cell treatment within the past 12 months
• Exclude those who have used other investigational drugs within the past 4 weeks
• 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.
• Having a history of alcohol dependence or drug addiction
• Pregnant or lactating female participants
• The situations that were determined by the investigator to be unsuitable for inclusion in the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai

Identifiers

NCT: NCT07195825 · BBM003-CLN001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗