NouvNeu001 human dopaminergic progenitor cell injections for advanced Parkinson's disease.

A Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Feasibility, and Preliminary Efficacy of NouvNeu001 in Patients With Advanced Parkinson's Disease.

We will try injecting NouvNeu001 (human dopaminergic progenitor cells) into the brain of people with advanced Parkinson's to see if it is safe, tolerable, feasible, and may improve symptoms.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 30 Years to 75 Years
• Sex: All
• Sponsor: iRegene Therapeutics Co., Ltd. (industry)
• Drugs / interventions: radiation, prednisone
• Locations: 1 site (New York, New York)
• Trial ID: NCT07102342 on ClinicalTrials.gov

What this trial studies

This phase 1/2, open-label, single-arm trial will transplant NouvNeu001 cells into the bilateral putamen/striatum using stereotactic neurosurgery at specialized centers. Participants will take immunosuppressive drugs for 24–36 weeks to reduce the risk of immune rejection and will be followed closely for safety, tolerability, feasibility, and early signs of efficacy. Eligible participants have moderate-to-advanced Parkinson's with documented levodopa responsiveness and stable dopaminergic medication prior to enrollment. Primary outcomes focus on safety and feasibility with exploratory motor and functional measures to detect preliminary benefit.

Who should consider this trial

Good fit: Ideal candidates are people aged 30–75 with Parkinson's for 4–20 years, H–Y stage 2.5–4 off, MDS-UPDRS-III >35 with >30% improvement on an acute levodopa challenge, stable dopaminergic therapy, and who are medically fit for neurosurgery.

Not a fit: Patients with very early disease, those who do not respond to levodopa, those with major medical or surgical contraindications, or those unwilling to undergo long-term immunosuppression are unlikely to benefit.

Why it matters

Potential benefit: If successful, the grafted cells could replace lost dopamine-producing neurons and lead to meaningful improvement in motor symptoms and reduced dependence on medications.

How similar studies have performed: Cell-replacement approaches for Parkinson's (including fetal grafts and pluripotent stem cell–derived dopaminergic cells) have shown promising signals in early-phase and preclinical work but remain unproven in larger controlled trials.

Eligibility criteria

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

Where this trial is running

New York, New York

• Cornell University Weill Medical College — New York, New York, United States (RECRUITING)

Study contacts

• Study coordinator: Meng Cai, Ph.D

Conditions: Parkinson Disease, NouvNeu001, Human Dopaminergic Progenitor Cells Injection, phase 1 study, Dopaminergic Progenitor Cells