NCT07267065尚未招募1 期
An Open-label Safety and Efficacy Study of AAV2-hAADC Administered by MRI-Guided Convective Infusion Using a Transfrontal Trajectory Into the Putamen and Caudate of Participants With Young Onset Parkinson's Disease
Krzysztof Bankiewicz2 个研究点 分布在 1 个国家目标入组 9 人开始时间: 2026年8月1日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- C-SSRS
研究概览
简要总结
This study is looking at whether a gene therapy called AAV2-hAADC is safe and may help people with Parkinson's Disease.
AAV2-hAADC is intended to increase the levels of dopamine in your brain. It contains a virus called adeno-associated virus 2 (AAV2) that has been modified to carry the genetic code for an enzyme called Aromatic L-Amino Acid Decarboxylase, or AADC for short.
In this study, AAV2-hAADC is delivered to two parts of the brain called the putamen and the caudate. Increasing the amount of AADC gene in these parts of the brain converts more levodopa into dopamine, the chemical that is lacking in PD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female adults 18-75 years of age (inclusive), at the time of signing the informed consent.
- •Diagnosed with idiopathic Parkinson's Disease as defined by the following:
- •a. Presence of bradykinesia PLUS any of the following: i. Rigidity ii. Resting tremor iii. Postural instability
- •Disease duration since diagnosis of >3 years.
- •Patient reported symptom onset prior to the age of 50 (inclusive).
- •Modified Hoehn & Yahr Staging ≥2.5 in the practically defined OFF medication state (≥ 12 hours from last dose of anti-parkinsonian medications)
- •Disabling motor complications with an average of ≥3 hours of OFF time per day during waking hours within 7 days of the screening visit as confirmed by the Parkinson's Disease (PD) diary.
- •International Parkinson and Movement Disorder Society (MDS) Unified Parkinson's Disease Rating Scale (UPDRS) Part III (total motor) score ≥25 in the clinically defined OFF state.
- •Unequivocal responsiveness to dopaminergic therapy for a minimum of 1 year, including a 30% or greater improvement in the UPDRS III (motor score) between ON and OFF states, as determined by the Investigator after overnight withdrawal of Parkinson's medications.
- •In the judgment of the Investigator, a stable, optimal regimen of Parkinson's medications for at least 4 weeks prior to screening evaluation.
- •In the judgment of the Investigator, stable Parkinson's features and symptoms for at least 4 weeks prior to screening evaluation.
- •Laboratory values prior to surgery:
- •Platelets >100E9/L (transfusion independent)
- •Prothrombin time (PT)/partial thromboplastin time (PTT) in normal range and international normalized ratio (INR) ≤1.3
- •Absolute neutrophil count >1.5E9/L
- •Hemoglobin >10.0 g/dL
- •Aspartate aminotransferase or alanine aminotransferase <2.5U/L × the upper limit of normal
- •Total bilirubin <2.5 mg/dL
- •Serum creatinine ≤1.5 mg/dL
- •Hematocrit >34%
- •White blood cell count <12E9/L
- •Estimated glomerular filtration rate ≥30 mL/min.
- •Medically and cognitively capable of comprehending and signing the informed consent, as well as undergoing and complying with the surgical procedure and protocol requirements as determined by review of medical records, medical history, and clinical evaluation.
- •Ability to travel to study visits alone or able to designate a care partner who agrees to accompany the participant to study visits as determined by discussion with the participant, care partner (if applicable), and Investigator.
- •Agrees to defer any neurological surgery, including deep brain stimulation, until the 12-month study visit is completed.
排除标准
- •Atypical or secondary parkinsonism, including but not limited to symptoms resulting from trauma, brain tumor, infection, cerebrovascular disease, other neurological disease, or to drugs, chemicals, or toxins, as determined by the Investigator.
- •Presence of clinically significant cognitive impairment as defined by a Montreal Cognitive Assessment (MoCA) score of less than 241 at screening and/or clinical diagnosis of dementia by Investigator based on MoCA diagnostic criteria.
- •Presence or history of psychosis, except for minor psychosis.
- •Presence of severe depression, as indicated by a BDI-II score >28 within 5 years of screening evaluation.
- •Active suicidal ideation as indicated by positive response to items 4 or 5 on the screening C-SSRS, or any history of a suicide attempt
- •Presence of impulse control disorder, defined as a total score ≥10 on the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS).
- •History of substance use disorder within 2 years of screening evaluation, as determined from interview with the participant and/or review of medical records.
- •Brain imaging abnormalities in the striatum or other regions that would substantially increase risk of surgery in the opinion of the investigator.
- •Contraindication to magnetic resonance imaging (MRI) and/or gadolinium (e.g., ProHance [gadoteridol]).
- •Coagulopathy or inability to temporarily stop any anticoagulation or antiplatelet therapy for at least 2 weeks during the perioperative period.
- •Prior stereotactic brain surgery including lesioning procedures, deep brain stimulation, infusion therapies or any other prior brain surgery that could complicate the study procedure and/or negatively impact study evaluations as determined from participant interview, screening MRI, and/or review of medical records.
- •Prior gene transfer, as determined from participant interview or review of medical records.
- •History of stroke, poorly controlled or significant cardiovascular disease, diabetes, or any other acute or chronic medical condition that would unreasonably increase the risks of the study procedures, as determined from interview with the participant and/or review of medical records.
- •History of malignancy other than treated carcinoma in situ within 3 years of screening evaluation.
- •Clinically apparent or laboratory-detected infection (including acute or chronic scalp infection) at the time of screening or baseline evaluations or immediately prior to surgery that would be a contraindication to surgery.
- •Prior or current treatment with any investigational agent within 5 half-lives or 30 days (whichever is shorter).
- •Any factors, medical or social, which would likely cause the inability to comply with the procedures of the protocol, including completion of Parkinson's Disease (PD) diaries, frequent and prolonged study visits (including off medication visits) and travel, in the judgment of the Investigator.
- •Chronic immunosuppressive therapy, including chronic steroids, immunotherapy, cytotoxic therapy, and chemotherapy as determined by participant interview and/or medical record.
- •Any serious medical condition or abnormal finding on physical examination or laboratory investigation that would substantially increase the risks of the study procedures in the opinion of the investigator.
- •Any medical condition that is likely to lead to disability during the study and interfere with or confound study assessments (including but not limited to orthopedic conditions, spinal disorders, neuropathy, myelopathy, severe pulmonary or cardiac disease, and compromised nutritional states), as determined from interview with the participant and/ or review of medical records.
- •Pregnant and lactating women.
- •Male or female with reproductive capacity who is unwilling to use barrier contraception for 6 months after surgery.
- •Ongoing treatments that might interfere with interpretation of the study outcome, including antipsychotic medications, apomorphine, or levodopa infusion therapy (Duopa).
- •Plans to participate in any other therapeutic intervention study within 12 months after surgery.
研究组 & 干预措施
Dose 1 (Low Dose)
Experimental
Total Dose (vg): up to 4.2E12
干预措施: AAV2-hAADC (Drug)
Dose 2 (High Dose)
Experimental
Total Dose (vg): up to 1.3E13
干预措施: AAV2-hAADC (Drug)
结局指标
主要结局
C-SSRS
时间窗: Through 3 year Follow-up
Changes in Columbia-Suicide Severity Rating Scale (C-SSRS) results
Adverse Events
时间窗: Through 3 year Follow-up
Assessment of AEs or SAEs and their relationship to the study procedure and study drug (graded as definite, probable, possible, unlikely, or unrelated).
MRI findings
时间窗: Through Month 6 Follow-up
Intraoperative and post-operative MRI findings
Physical Exam and labs
时间窗: Through 3 year Follow-up
Changes from baseline in physical examination findings and routine clinical laboratory analysis (hematology, clinical chemistries, immunologic assessments).
次要结局
未报告次要终点
研究者
Krzysztof Bankiewicz
Professor
Ohio State University
研究点 (2)
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