Clinical trial NCT06167681: The Safety, Tolerability and Efficacy of NouvNeu001 for Parkinson's Disease
Official title: A Phase I/II Study to Assess the Safety, Tolerability and Efficacy of NouvNeu001 Injection for Mid- to Late-stage Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Parkinson Disease
Keywords: Parkinson Disease
Dopaminergic Progenitor Cells
Lead sponsor: iRegene Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-12-12
Enrollment: 40
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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
* 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
* 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 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 or with severe anxiety during screening;
* Patients with the following abnormalities during screening, including: Abnormal coagulation; Abnormal immunological tests, and assessed by the investigator it is not suitable to participate in the trial; Hypertensive patients with poorly controlled blood pressure and patients with severe postural hypotension; Diabetic patients with poorly controlled blood glucose
* Patients with surgical contraindications, 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)
* 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 or any of its components, or are allergic to the same drugs or other macrolides, or have allergies;
* 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

Primary outcomes:
measure: Safety and Tolerability
timeFrame: 24 weeks and 48 weeks post-transplant
measure: Motor Function
timeFrame: 24 weeks post-transplant
Secondary outcomes:
measure: The Motor Function and Non-motor Function
timeFrame: 48 weeks and 96 weeks post-transplant
measure: Continued Safety and Tolerability
timeFrame: 96 weeks and 5 years post-transplant
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
Study officials:
References: