Parkinson Disease
Conditions
Keywords
NouvNeu001, Human Dopaminergic Progenitor Cells Injection, phase 1 study, Dopaminergic Progenitor Cells
Brief summary
This is a phase 1/2 clinical study to evaluate the safety, tolerability, feasibility, and preliminary efficacy of NouvNeu001 in patients with advanced Parkinson's Disease.
Detailed description
This is a multi-center, single arm, and open label trial. The NouvNeu001 will be transplanted into the bilateral putamen/striatum using stereotactic neurosurgery. Subjects will take immunosuppressants to prevent potential immune rejection for 24 to 36 weeks.
Interventions
BIOLOGICALHuman Dopaminergic Progenitor Cells
Single injection of Human Dopaminergic Progenitor Cells into the biliteral putamen/striatum regions of the brain
Sponsors
iRegene Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Age • Male or female patient must be 30 to 75 years of age inclusive, at the time of signing the informed consent form (ICF). Type of Patient and Disease Characteristics * Diagnosis of PD between past 4 to 20 years (meet MDS 2015 clinical diagnostic criteria for PD). * H-Y staging (Appendix III) for "OFF" episodes is 2.5-4.0. * MDS-UPDRS-III score \> 35, and positive for the Acute levodopa challenge test (ALCT) (improvement \> 30% for MDS UPDRS-III staging from OFF episodes to ON episodes) over two screening period visits. Baseline scores will be computed as the means of two screening period visits. * No significant change in UPDRS-III scores between the two visits during the screening period. * Patients who take stable doing of dopamine drug for at least 4 weeks prior to receiving the study drug. * No significant change in dose and dosing schedule of the prescribed medicines for PD during the screening period. * Medically suitable for neurosurgery under general anesthesia. * Acceptable laboratory test values during screening and prior to transplantation (Day 0): * Absolute neutrophil count ≥ 2.0 × 109/L * White blood cell count ≥ 4.0 × 109/L * Platelet count ≥ 100 × 109/L * Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) * Total bilirubin ≤ 1.5 x ULN * Serum creatinine ≤ 1.5 x ULN * eGFR ≥ 50 mL/min/1.73 m2 * Agree to postpone any additional neurosurgical procedures, including DBS, until completion of the 12-month follow-up study (unless recommended by a neurologist). * Agree not to participate in any other therapeutic intervention study within 24 months after neurosurgery. * Able to participate in all study visits and evaluations, including brain/spine MRI, CT and PET scan. Weight • Body mass index (BMI) within the range of 18\~32 kg/m2 (inclusive) with a minimum body weight of 45 kg at screening. Sex and Contraceptive/Barrier Requirements • Contraceptive use by men and women for 12 months after neurosurgery should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Informed Consent * Able to understand the rationale of the clinical trial and sign the ICF. Other Inclusion Criteria * Agree not to receive COVID-19 vaccine within 14 days before neurosurgery, and not to receive any other vaccine within 30 days after neurosurgery
Exclusion criteria
Medical Conditions * Atypical Parkinsonism (Parkinsonism-Plus syndrome, secondary parkinsonism, familial parkinsonism) Prior/Concomitant Therapy * Patients who have had previous pallidotomy, DBS surgery, striatal or extrapyramidal surgery, brain stereotaxy, prior surgical or radiation therapy to the brain or spinal cord, or other brain surgery; as well as other surgical procedures that, in the investigator's judgment, could interfere with participation in this study. * Patients who have a previous head CT/MRI examination showing cerebral trauma, vascular malformation, hydrocephalus, brain tumor, etc., and patients who have brain imaging abnormalities in the striatum or other brain areas leading to a significantly increased risk for surgery. * Patients who have had previous cellular therapy. * Patients who have used glucocorticoids for an extended period (≥14 days) and at high doses (equivalent to prednisone ≥ 20 mg/day or other glucocorticoids at equivalent doses) within 3 months prior to signing the ICF. (excluding topical treatment) * Patients who have used immunosuppressive drugs for an extended period (≥14 days) within 3 months prior to signing the ICF. * Patients who have used antipsychotics, such as antidepressants, antimanic drugs, etc. within 3 months prior to signing the ICF and are deemed by the investigator to potentially impact the study assessment. * Patients who have used botulinum toxin or other drugs for dystonia or muscle spasticity within 6 months prior to signing the ICF and are deemed by the investigator to potentially impact the study assessment. Prior/Concurrent Clinical Study Experience * Patients who are participating in other clinical trials, or have been enrolled in other clinical studies within 3 months prior to the screening * Patients with poor compliance based on clinical evaluation of the investigator. Diagnostic Assessments * Patients with a history of dementia or a severe cognitive disorder; or those with obvious dementia or congnitive impairment detected during screening; MDS-UPDRS congnitive impairment score (section 1.1) \> 3 point at screening; or patinets with poor compliance, inability to accurately keep diary, and/or inability to sign ICF due to dementia. * Severe depression as defined by HAMD ≥ 24 at screening. * Severe anxiety as defined by HAMA ≥ 29 at screening. * Patients with a history of psychiatric disorders that, in the investigator's opinion, make them unsuitable for participation; or patients with a history of suicidal ideation or suicide attempts within the past year or currently (including actual attempts, interrupted attempts, or failed attempts). * Patients with abnormal coagulation (prothrombin time ≥ 1.5 ULN, activated partial thromboplastin time ≥ 1.5 ULN), or abnormal INR at screening. * Patients cannot temporarily suspend anti-platelet agents or other anti-coagulant medications at least 5 days prior to investigational drug administration surgery. * Patients with active disseminated intravascular coagulation and significant hemorrhagic tendency within 3 months prior to signing the ICF. * Patients with current or history of following disease * severe heart failure (congestive heart failure of New York Heart Association Class II or above), unstable angina pectoris, and myocardial infarction * severe arrhythmia, including but not limited to second- or third-degree atrioventricular block, or prolonged QT interval. * Long QT Syndrome. * cardiovascular surgery (cardiac, vascular stent surgery, angioplasty). * stroke or transient ischemic attack within 3 months prior to signing the ICF, as determined by the investigator to be unsuitable to participate the study. * subarachnoid hemorrhage * primary mitochondrial disorder, multiple sclerosis, or other neurodegenerative diseases such as Alzheimer's disease * major vascular diseases (aortic aneurysm, aortic dissecting aneurysm, internal carotid artery stenosis), as determined by the investigator to be unsuitable to participate the study. * previous or current malignant tumors * immune disfunction, including autoimmune disease or immunocompromised state * traumatic brain injury with loss of consciousness and residue neurologic symptoms * active epilepsy or currently on anti-epileptic drugs * Hypertensive patients with poorly controlled blood pressure (defined as blood pressure above 160/100 mmHg despite antihypertensive drugs treatment) and patients with severe postural hypotension * Diabetic patients with poorly controlled blood glucose (glycosylated hemoglobin \> 9.0%, or fasting plasma glucose (FPG) ≥ 11.1mmol/L) * Patients with clinically significant abnormalities in kidney or liver function at screening. * Patient with clinically significant abnormalities in immunological tests at screening * Patients with surgical contraindications (such as those with cochlear implant, cardiac pacemaker, cardiac defibrillator, stereotactic nucleus pallidotomy; Patients who have had unilateral or bilateral intraparenchymal implantation of cellular products, or other surgical procedures within 6 months before screening which, in the opinion of the investigator, have an impact on this trial; Patients with other neurosurgical contraindications) * Patients with other combined severe systemic diseases, such as pulmonary heart disease, moderate to severe asthma, severe chronic obstructive pulmonary disease (COPD) (FEV1% \< 50%) * Patients with serious infections, requiring antibiotic treatment within 2 weeks prior to signing the ICF * Patients with any active infectious disease, including but not limited to positive for human immunodeficiency virus, SARS Covid-19 virus, syphilis antibody, quantitative HCV-RNA testing, quantitative HBV-DNA testing greater than normal range for test results, or untreated tuberculosis; any other active infection that, in the investigator's opinion, may affect the participant's ability to take part in the study or could impact study outcomes. Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 24 weeks and 48 weeks post-transplant | Incidence and severity of adverse events (AEs) and serious adverse events (SAEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Motor Function and Non-motor Function | 48 weeks and 96 weeks post-transplant | Changes in MDS-UPDRS Part I-IV Score from baseline to 48 weeks and 96 weeks post-transplant. A higher score indicates more severe symptoms or worse health. |
| Continued Safety and Tolerability | 96 weeks and 15 years post-transplant | Incidence and severity of AEs and SAEs within 96 weeks and 15 years post-transplant. |
Countries
United States
Contacts
CONTACTMeng Cai, Ph.D
CONTACTJing Zhao, PhD
Outcome results
None listed