Open-Label, Multi-Stage Study to Optimize the Intraputaminal Administration of AB-1005 Using a Prescriptive Infusion Algorithm (PIA)

Korábbi kezelés

• Presence or history (within 2 years prior to screening) of substance use disorder (including alcohol) as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria (or in the judgment of the neurologist)
• Stroke, transient ischemic attack, or other suspected cerebrovascular accident within 1 year prior to screening
• Unstable angina pectoris or myocardial infarction within 1 year prior to screening
• Revascularization procedure(s) within 1 year prior to screening
• Inability to identify a safe trajectory to each putamen via an occipitoparietal entry point, or known contraindications to brain surgery in prone position (as determined by the neurosurgeon)
• Concurrent use of percutaneous levodopa/carbidopa intestinal gel, subcutaneous levodopa, or apomorphine pump
• Chronic immunosuppressive therapy
• History of prior cell or gene therapy
• Participation in other interventional clinical trials within 12 weeks prior to screening or unwilling to refrain from starting new investigational agents throughout the course of the study
• Unwilling to defer any vaccination from screening through 1 month after surgery

Más betegség

• Presence or history of psychosis or impulse control disorder (as determined by the neurologist)
• Current suicidal ideation as indicated by positive response to items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C SSRS), or any history of a suicide attempt
• Clinically significant cognitive impairment (Montreal Cognitive Assessment \[MoCA\] score \<25)
• Presence or history of malignancy other than treated cutaneous squamous or basal cell carcinomas
• Presence of clinically active infection, including acute or chronic scalp infection
• Presence or history of significant cerebrovascular or cardiovascular disease, including:
• Poorly controlled hypertension, poorly controlled diabetes mellitus or prediabetes mellitus with known significant microvascular injury, or other significant cardiovascular history or risk factor
• Known history of complications of anesthesia including difficult airway management and/or difficult endotracheal intubation, malignant hyperthermia, or other related issues that would compromise participant safety during general anesthesia (as determined by the anesthesiologist)
• Known allergy or sensitivity to ingredients in the intervention formulation and/or to gadolinium-based contrast agents
• History of brain surgery (including deep brain stimulation \[DBS\] or focused ultrasound)

Laborértékek

• Laboratory values at screening:
• Platelets ≤100,000/mm3
• PT \>15 s, aPTT \>40 s, and/or INR \>1.3
• Absolute neutrophil count (ANC) ≤1500/mm3
• Hemoglobin ≤10.0 g/dL
• Total bilirubin ≥2.5 mg/dL
• eGFR \<45 mL/min/1.73 m2
• HbA1C ≥8%

Egyéb

• Evidence of secondary or atypical parkinsonism (as determined by the neurologist)
• Presence of untreated or sub optimally treated depression (Beck Depression Inventory \[BDI\]-II score ≥20)
• Known contraindications to MRI
• Aspartate aminotransferase or alanine aminotransferase ≥2.5 times the upper limit of normal
• Unable to comply with the protocol procedures, including frequent and prolonged follow-up assessments (during LTFU study ASK-PD0-CS002)
• Any significant issue raised by the neurologist, neurosurgeon, or anesthesiologist that may make a participant unsuitable for the study

• Participant must be 45 to 75 years of age inclusive, at the time of signing the informed consent.
• \>10 years since diagnosis of PD (at time of consenting / Screening Visit 1)
• Presence of bradykinesia plus any of the following:
• Rigidity
• Resting tremor
• Postural instability
• Modified Hoehn and Yahr stage III-IV in the practically defined OFF state
• Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score \>40 in the practically defined OFF state
• Stable anti-PD medication regimen for at least 4 weeks prior to Screening Visit 1 and through Baseline Visit
• ≥30% reduction in MDS-UPDRS Part III following a levodopa challenge
• Must agree to use barrier method protection when engaging in intercourse/sexual activity with another person for at least 3 months post-dosing.
• Male participants must refrain from donating sperm for at least 3 months post-dosing.
• Female participants cannot be pregnant or breastfeeding at the time of screening. A woman of childbearing potential (WOCBP) must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) at the required assessments
• Provision of signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• Provision of signed consent to also participate in LTFU study ASK-PD0-CS002