Patients with advanced Parkinson'
Conditions
Interventions
GT0003X consists of three types of adeno-associated virus (AAV2) vectors. It is administered via stereotactic brain surgery with a dedicated catheter for targeted injection into the striatum (putamen)
GT0003X
Sponsors
Inter Pharma Plc.
Eligibility
Sex/Gender
All
Age
40 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1) Patients diagnosed with Parkinson's disease according to the Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson's Disease 2) Patients aged 40 to 80 years at the time of consent 3) Patients aged 35 years or older at onset 4) Patients with a history of treatment with Levodopa (L-dopa) for 5 years or more. Even if the five-year period is not met, if the principal investigator or sub-investigator determines that the patient is in the advanced stage of Parkinson's disease, the possibility of inclusion may be discussed with the coordinating investigator. 5) Patients who do not achieve satisfactory therapeutic effects whose symptoms remain inadequately controlled despite receiving a total daily levodopa equivalent dose exceeding 1,000 mg, or frequent administration of levodopa with five or more times per day 6) Patients with Hoehn and Yahr severity stage 4 or higher in the OFF state at the time of consent 7) Patients with a total score (OFF state) of 30 to 100 points on the The Movement Disorder Society-The Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-III (motor score) at baseline 8) Patients who have a positive response to dopaminergic therapy as evidenced by a decrease in MDS-UPDRS-III (motor scores) between the defined OFF and ON states: a minimum of 16 points improvement in the UPDRS after dopaminergic therapy. 9) Patients with intolerable motor complications with a total score of 4 points or more on the MDS-UPDRS-IV item B (fluctuation of motor symptoms) at baseline 10) Patients who do not have dementia, as assessed by a Montreal Cognitive Assessment (MoCA) score of >= 25 11) Patients who can undergo stereotactic brain surgery 12) Patients who can comply with the necessary conditions of this clinical trial, including frequent medical examinations after administration of the investigational product 13) Patients who do not need to change their Parkinson's disease medication for at least 8 weeks before starting administration of the investigational product 14) Informed consent can be obtained from the patient 15) Patients who have not used the following drugs and treatments for at least 8 weeks before the administration of the investigational product: Antiepileptic drugs (excluding zonisamide), Immunosuppressants (excluding steroids), Anticoagulants (excluding heparin preparations used to prevent blood clotting in intravenous indwelling routes and arterial pressure lines), Antiplatelet drugs, Other investigational drugs, investigational devices, and investigational products, and Neurosurgical treatment. For patients using prohibited concomitant drugs and treatments, the possibility of inclusion may be discussed with the coordinating investigator, taking into consideration the patient's safety and the impact on the evaluation of the safety and efficacy of this investigational product, depending on the patient's condition.
Exclusion criteria
Exclusion criteria: 1) Patients with secondary or atypical parkinsonism suggested by a medical history of cerebrovascular disease, exposure to antipsychotics or toxins, or encephalitis, or by symptoms such as progressive supranuclear palsy, cerebellar symptoms, pyramidal signs, autonomic signs, dementia, hallucinations, or delusions, or by magnetic resonance imaging (MRI) findings such as lacunar infarction, atrophy of the midbrain tegmentum, or atrophy of the pons and cerebellum. 2) Patients who have already undergone stereotactic brain surgery (pallidal coagulation, thalamic coagulation, deep brain stimulation) or MR-guided focused ultrasound therapy for Parkinson's disease. 3) Patients with a score of 20 or less on the Mini-Mental State Examination (MMSE) or who have been diagnosed with dementia. 4) Patients with a history of schizophrenia or mood disorder. 5) Patients with obvious cardiovascular disease, including cerebrovascular disease. 6) Patients with central nervous system tumors or clinically obvious neurological diseases e.g., significant brain atrophy not consistent with age). 7) Patients with malignant tumors or a history of other malignant tumors, except for treated skin cancer, within 5 years prior to obtaining informed consent. 8) Patients with uncontrolled hypertension. 9) Patients with blood coagulation disorders or those requiring antithrombotic therapy. 10) Patients with clinically evident immune abnormalities requiring administration of immunosuppressants (excluding steroids). 11) Patients with a Geriatric Depression Scale - short form (GDS-S) score of 10 or more, or 5 or more if taking antidepressants. 12) Patients who cannot undergo MRI scans. 13) Patients who wish to have children, except those who freeze and store sperm or eggs before administering the investigational product and use them to have children. 14) Patients with a history of seizures within 3 years, patients taking antiepileptic drugs, or patients with epilepsy abnormalities confirmed by electroencephalogram (EEG). For patients taking antiepileptic drugs, the possibility of inclusion may be discussed with the coordinating investigator, taking into consideration the patient's safety and the impact on the evaluation of the safety and efficacy of the investigational product, depending on the patient's condition. 15) Patients with a history of hypersensitivity to the ingredients used in the manufacturing process of this investigational product (Sf-RVN and benzonase) or to any of the ingredients in this investigational product. 16) Patients with a history of severe drug allergies. 17) Patients who have participated in other clinical trials or clinical research involving interventions within 24 weeks prior to this registration. 18) Patients with the following diseases that are difficult to control: i. Severe renal impairment (serum creatinine > 2.0 mg/dl and blood urea nitrogen (BUN) > 25 mg/dl) ii. Severe liver impairment (aspartate aminotransferase (AST) / glutamate oxaloacetate transaminase (GOT) or alanine aminotransferase (ALT) / glutamate pyruvate transaminase (GPT) 2.5 times or more the upper limit of normal) iii. Diabetic patients who are difficult to control (casual or postprandial blood glucose > 200 mg/dl and HbA1c > 9%) 19) Patients who are otherwise deemed inappropriate for this clinical trial by the principal investigator. 20) Patients who are pregnant or those who may be pregnant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety the time of administration through the end of the study follow-up period (week 24) Adverse events occurrence: any undesirable or unintended sign, symptom, or illness that occurs in a participant, regardless of whether it is related to the investigational product., Motor functions at baseline and week 24 MDS-UPDRS Part III (ON, OFF) total score | — |
Secondary
| Measure | Time frame |
|---|---|
| Motor and non-motor functions at baseline and week 24 Scores for each part of the MDS-UPDRS (during ON and OFF),Parkinson's disease symptoms at baseline and week 24 The proportion of OFF time in awake time (MDS-UPDRS),Parkinson's disease symptoms at baseline and week 24 The proportion of ON time (ON time with dyskinesia and ON time without dyskinesia) in awake time (MDS-UPDRS),Severity of Parkinson's disease at baseline and week 24 Hoehn & Yahr severity scale in MDS-UPDRS during OFF time,Cognitive function at baseline and week 24 Mini Mental State Exam (MMSE) score,Cognitive function at baseline and week 24 Montreal Cognitive Assessment (MoCA) score, Depression at baseline and week 24 Geriatric Depression Scale Short Form (GDS-S) score,Suicidal ideation at baseline and week 24 The Columbia Suicide Severity Rating Scale Scoring (C-SSRS),Parkinson's Disease medication requirement at baseline and week 24 Equivalent dose of L-dopa,Parkinson's disease symptoms at baseline and week 24 The percent day spent in mobile state (Subject diary), Quality of life at baseline and week 24 Parkinsons Disease Questionnaire (PDQ 39) score | — |
Countries
Thailand
Contacts
Public ContactHathaigan Chiraphitakkun
Inter Pharma Plc.
Outcome results
None listed