The Safety, Tolerability and Efficacy of NouvNeu001 for Parkinson's Disease

Study Overview
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Brief Summary
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This clinical trial is designed to evaluate the safety, tolerability and preliminary efficacy of a single injection of NouvNeu001 (Human Dopaminergic Progenitor Cells Injection) in patients with Parkinson's disease.

Detailed Description
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This is a multi-center, single arm, and open label trial. The NouvNeu001 will be transplanted into bilateral putamen/striatum using stereotactic neurosurgery. Subjects will take immunosuppressants to prevent potential immune rejection for 24 to 36 weeks.

Official Title
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A Phase I/II Study to Assess the Safety, Tolerability and Efficacy of NouvNeu001 Injection for Mid- to Late-stage Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Biological: Human Dopaminergic Progenitor Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50-75 years old, male or female Able to understand the rationale of the clinical trial and sign informed consent form (ICF) Diagnosis of Parkinson's Disease in accordance with the MDS clinical diagnostic criteria for Parkinson's disease (2015) Diagnosis of Parkinson's Disease made between 4 to 20 years ago Medically suitable for neurosurgery under anesthesia and able to participate in Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) scan. Hoehn-Yahr staging for off episodes is 2.5 to 4 The MDS-UPDRS Part III (MDS-UPDRS-III) score in the off state > 35, and positive for the Acute Levodopa Challenge Test (ALCT) Acceptable laboratory test results during screening and prior to transplantation Exclusion Criteria: Atypical Parkinsonism (Parkinsonism-Plus syndrome, secondary parkinsonism, hereditary parkinsonism) Patients who have had previous pallidotomy, deep brain stimulation (DBS) surgery, striatal or extrapyramidal surgery, brain stereotaxy or other brain surgery; as well as other surgical procedures that are judged by the investigator to affect patient's 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 with a history of severe cardiovascular and cerebrovascular diseases Patients with a history of malignant tumors Patients who have had previous cellular therapy Patients with active disseminated intravascular coagulation and significant hemorrhagic tendency within 3 months prior to screening, or who cannot temporarily suspend anti-platelet agents or other anti-coagulant medications for at least 5 days before surgery Patients with long-term, heavy use of glucocorticoids or immunosuppressive drugs within 3 months prior to signing the ICF (except for topical use) Patients with a history of mental illness who are deemed unfit to participate in the study by the investigator; or a history of suicidal ideation or suicide attempts (including actual attempts, interrupted attempts, or failed attempts) within the past year or currently; Patients who have used botulinum toxin within 6 months prior to signing the ICF Patients with active epilepsy or currently on anti-epileptic drugs Patients with a history of dementia or severe cognitive disorder, or the score of MDS-UPDRS 1.1 during screening is > 3; poor compliance, inability to accurately keep diary, and/or inability to sign ICF due to dementia Patients with severe depression (defined as Hamilton Depression Scale [HAM-D17]≥24 ) or with severe anxiety (defined as Hamilton Anxiety Scale [HAMA]≥29) during screening; Patients with the following abnormalities during screening, including: Abnormal coagulation (prothrombin time ≥1.5 ULN, activated partial thromboplastin time ≥1.5 ULN); Abnormal immunological tests, and assessed by the investigator it is not suitable to participate in the trial; 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 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 with 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%) Presence of one of the following: positive for human immunodeficiency virus (HIV) antibody, treponema pallidum antibody, hepatitis C virus (HCV) antibody and HCV RNA; Hepatitis B virus (HBV) surface antigen positive and HBV DNA copy number > detection of normal values; Tuberculosis is in the active stage; Other active infections that the investigator believes may affect Patients' participation in the study or affect study outcomes; Patients with alcohol addiction or positive for drug of abuse testing Patients with a history of contraindication or allergy to the drugs used during the study (such as immunosuppressants, levodopa, etc.) or any of its components, or are allergic to the same drugs or other macrolides, or have allergies (such as allergies to two or more drugs or foods); Female of childbearing potential who are not surgically sterilized/premenopausal/unwilling to use medically approved effective contraception with 2 years after administration of investigational drug and lactating women; men who are not surgically sterilized/unwilling to use medically approved effective contraception with 2 years after administration of investigational drug Patients who have received electric shock therapy within 30 days prior to surgery Patients who are participating in other clinical trials, or have been enrolled in other clinical studies and received intervention therapy within 3 months prior to the surgery Patients with poor compliance based on clinical evaluation of the investigator Patients who are being treated with drugs such as apomorphine, or levodopa/carbidopa infusion therapy Patients with severe dyskinesia in both on- and off-drug states Patients with significant medical conditions, or with other conditions that, in the opinion of the investigator, endangers the safety of the patient or affects the investigator's assessment

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NouvNeu001<br> | Biological: Human Dopaminergic Progenitor Cells<br>* Single injection of Human Dopaminergic Progenitor Cells into the putamen/striatum region of brain.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Incidence and severity of adverse events (AEs) and serious adverse events (SAEs). | 24 weeks and 48 weeks post-transplant | 
| Motor Function | Changes in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part Ⅲ score from baseline to 24 weeks post-transplant. MDS-UPDRS Part III assesses the motor signs of PD, a higher score indicates more severe symptoms of PD. | 24 weeks post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Motor Function and Non-motor Function | Changes in MDS-UPDRS Part I-IV, Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAM-D17), Pittsburgh Sleep Quality Index (PSQI) and Parkinson's Disease Quality of Life Questionnaire (PDQ-39) Score from baseline to 48 weeks and 96 weeks post-transplant. A higher score indicates more severe symptoms or worse health. | 48 weeks and 96 weeks post-transplant | 
| The Modified Hoehn Yahr Score | Changes in the Modified Hoehn Yahr score from baseline to 48 weeks, 96 weeks and 5 years post-transplant. The Modified Hoehn and Yahr scale measures the severity of Parkinson's disease by assessing the patient's motor symptoms and functional impairment. The scale has seven stages, ranging from 1 to 5, with higher scores indicating more severe disease. | 48 weeks, 96 weeks and 5 years post-transplant | 
| Off Time | Changes in Waking Hours in off State from baseline to 48 weeks, 96 weeks and 5 years post-transplant. | 48 weeks, 96 weeks and 5 years post-transplant | 
| L-dopa Equivalent Dose | Changes in oral L-dopa Equivalent Dose from baseline to 48 weeks and 96 weeks post-transplant. | 48 weeks and 96 weeks post-transplant. | 
| Continued Safety and Tolerability | Incidence and severity of AEs and SAEs within 96 weeks and 5 years post-transplant. | 96 weeks and 5 years post-transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson Disease, Dopaminergic Progenitor Cells