This Clinical Trial is Designed to Evaluate the Safety, Tolerability, Feasibility and Preliminary Efficacy of NouvNeu001 (Human Dopaminergic Progenitor Cells Injection) in Patients With Parkinson's Disease. (NouvNeu001-01)

iRegene Therapeutics

Status and phase

Not yet enrolling

Phase 1

Conditions

Parkinson Disease

Treatments

Biological: Human Dopaminergic Progenitor Cells

Study type

Interventional

Funder types

Industry

Identifiers

NCT07102342

NouvNeu001-01

Details and patient eligibility

About

This is a phase 1 clinical study to evaluate the safety, tolerability, feasibility, and preliminary efficacy of NouvNeu001 in patients with advanced Parkinson's Disease.

Full 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.

Enrollment

5 estimated patients

Sex

All

Ages

30 to 75 years old

Volunteers

No Healthy Volunteers

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 Exclusion Criteria

Patients with alcohol or drug addiction
Patients with contraindications or a history of allergy to any medicines used during the neurosurgical procedure.
Patients with contraindication or a history of allergy to any medicines used during the study, such as immunosuppressants, levodopa, etc, or any of their components; Patients who are allergic to similar drugs or other macrolides.
Female of childbearing potential who are not surgically sterilized/premenopausal/unwilling to use medically approved effective contraception during the study and lactating women; men who are not surgically sterilized/unwilling to use medically approved effective contraception during the study
Patients who have received electric shock therapy within 30 days prior to the investigational drug administration surgery
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
Patients who are being treated with drugs such as neuroleptics, apomorphine, or levodopa/carbidopa infusion therapy
Patients with severe dyskinesia in both "ON" and "OFF" drug states
Patients who have received or will receive a live vaccine within 4 weeks prior to the study
Patients with significant medical conditions, or with other conditions that, in the opinion of the investigator, are unsuitable to participate in the study