Phase I Clinical Study of NouvNeu001 Injection for the Treatment of Moderate-to-Advanced Parkinson's Disease in Patients Who Have Previously Undergone Deep Brain Stimulation or Deep Brain Nucleus Lesioning Surgery

Официальное название

Phase I Clinical Study to Evaluate the Safety and Efficacy of NouvNeu001 Injection for the Treatment of Moderate-to-Advanced Parkinson's Disease in Patients Who Have Previously Undergone Deep Brain Stimulation or Deep Brain Nucleus Lesioning Surgery

Обзор

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 who have previously undergone deep brain stimulation or deep brain nucleus lesioning surgery.

Вмешательства

• Биопрепарат NouvNeu001 injection
  NouvNeu001 injection is a Human Dopaminergic Progenitor Cell injection, administered as a single injection into the putamen/striatum region of the brain.

Первичные конечные точки

• Incidence and severity of Adverse Events as Assessed by CTCAE V5.0 [Срок оценки: 48 weeks post-transplant]

Вторичные конечные точки (7)

• Changes from baseline in the MDS Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score, as well as MDS-UPDRS Parts I, II, III (off state and on state), and IV scores at 12, 24, 36, 48, 72, and 96 weeks after administration. [Срок оценки: Weeks 12, 24, 36, 48, 72, and 96]
• Changes from baseline in the Modified Hoehn and Yahr Staging at 12, 24, 36, 48, 72, and 96 weeks after administration [Срок оценки: Weeks 12, 24, 36, 48, 72, and 96]
• Changes from baseline in the Hamilton Depression Rating Scale (HAMD) score at 12, 24, 36, 48, 72, and 96 weeks after administration [Срок оценки: Weeks 12, 24, 36, 48, 72, and 96]
• Changes from baseline in the Parkinson's Disease Questionnaire (PDQ-39) score at 12, 24, 36, 48, 72, and 96 weeks after administration [Срок оценки: Weeks 12, 24, 36, 48, 72, and 96]
• Changes from baseline in "off" time and "on" time at 12, 24, 36, 48, 72, and 96 weeks after administration [Срок оценки: Weeks 12, 24, 36, 48, 72, and 96]
• Changes from preoperative baseline in the daily oral levodopa equivalent dose (LEDD) of patients at 12, 24, 36, 48, 72, and 96 weeks after administration [Срок оценки: Weeks 12, 24, 36, 48, 72, and 96]
• Changes from baseline in Total Electrical Energy Delivered (TEED) at 12, 24, 36, 48, 72, and 96 weeks after administration [Срок оценки: Weeks 12, 24, 36, 48, 72, and 96]

Критерии участия

Критерии включения

• Age ≥18 years and ≤70 years, male or female.
• The subject understands and agrees to comply with the study procedures, voluntarily participates, and signs the informed consent form.
• Primary Parkinson's disease (meeting the diagnostic criteria of the International Parkinson and Movement Disorder Society \[MDS\]), and the subject has previously undergone deep brain stimulation (DBS) or deep brain nucleus lesioning surgery.
• With DBS turned off, the MDS Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) motor examination score in the "off" state is ≥30; and the levodopa challenge test is positive (improvement rate in UPDRS-III score ≥30%).
• Able to undergo neurosurgery under anesthesia, and able to undergo CT/MRI/PET examinations.
• At screening, with DBS turned on, the modified Hoehn and Yahr stage (Appendix 3) in the "off" state is between 2.5 and 4 (inclusive), and with DBS turned on, the daily "off" time is not less than 2 hours.
• Has received stable doses of anti-Parkinson's disease medications for at least 4 weeks prior to administration.
• Acceptable laboratory values obtained during the screening period and prior to administration (Day 0): Absolute neutrophil count ≥ lower limit of normal (LLN); White blood cell count ≥ LLN; Platelet count ≥ LLN; AST and ALT ≤ 2.5 × upper limit of normal (ULN); Total bilirubin ≤ 1.5 × ULN; Serum creatinine ≤ 1.5 × ULN; eGFR ≥ 50 mL/min/1.73 m².
• The subject agrees to postpone any other elective neurosurgical procedures until completion of the 12-month follow-up study.
• The subject agrees not to participate in any other interventional clinical studies within 12 months after administration.
• The subject agrees not to receive any vaccines within 30 days after administration.

Критерии исключения

• Atypical or secondary parkinsonism confirmed by the investigator to be caused by medication, metabolic disorders, or other conditions.
• Presence of persistent active infection in the previous brain surgery area, cerebrospinal fluid (CSF) leakage, or unhealed wounds; presence of implanted device malfunction, electrode displacement, etc., which in the investigator's judgment poses a significant risk to the subject or affects evaluation; contraindications to MRI (e.g., intracranial implants, cochlear implants, cardiac pacemaker/defibrillator, etc.); any contraindications to surgery or anesthesia as assessed by the investigator; or other surgical conditions that the investigator believes may affect participation in this study.
• Significant abnormalities on cranial CT/MRI, including but not limited to: cerebral vascular malformation, vasogenic edema, brain tumor, more than 10 microbleeds, basal ganglia cerebral infarction lesions, etc., which in the investigator's judgment significantly increase surgical risk.
• History of severe cardiovascular disease within 1 year prior to screening, including but not limited to: severe heart failure (New York Heart Association Class III or IV, or left ventricular ejection fraction <35% by any method), unstable angina pectoris, myocardial infarction, clinically significant conduction abnormalities (e.g., unstable atrial fibrillation), etc., which in the investigator's judgment may increase surgical risk or render the subject unsuitable for participation.
• History of malignant tumor, or receipt of cell therapy or gene therapy within 2 years prior to screening.
• Active disseminated intravascular coagulation (DIC) or significant bleeding tendency within 3 months prior to signing informed consent, or inability to discontinue antiplatelet or other anticoagulant medications for at least 5 days before surgery.
• Long-term (≥14 days) and high-dose (prednisone ≥20 mg/day or equivalent dose of other glucocorticoids) use of glucocorticoids or immunosuppressants (excluding topical use) within 3 months prior to signing informed consent.
• History of psychiatric illness that, in the investigator's judgment, makes the subject unsuitable for participation; or history of suicidal ideation or suicidal attempt (including actual attempt, interrupted attempt, or aborted attempt) within the past year or currently.
• Use of botulinum toxin within 6 months prior to signing informed consent.
• Active epilepsy or current use of antiepileptic drugs at screening.
• History of dementia or severe cognitive impairment; or obvious dementia or cognitive impairment at screening; MDS-UPDRS Part 1.1 (cognitive impairment) score >3 at screening; poor compliance, inability to accurately complete diaries, and/or inability to sign informed consent due to dementia.
• Severe depression, anxiety, or severe dysphagia at screening.
• Any of the following abnormal laboratory findings at screening, including but not limited to: Clinically significant abnormalities in coagulation function (prothrombin time ≥1.5 × ULN, activated partial thromboplastin time ≥1.5 × ULN); Clinically significant immunological abnormalities or autoimmune disease, assessed by the investigator as unsuitable for trial participation; Poorly controlled hypertension (defined as blood pressure still >160/100 mmHg despite antihypertensive treatment) and severe orthostatic hypotension; Poorly controlled diabetes mellitus (HbA1c >9.0%, or fasting plasma glucose \[FPG\] ≥11.1 mmol/L).
• Other severe systemic diseases, such as cor pulmonale, severe chronic obstructive pulmonary disease (COPD) (FEV1% <50%), etc.
• Presence of human immunodeficiency virus (HIV) infection, syphilis infection, active hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, tuberculosis infection, or other active infections that the investigator believes may affect the subject's participation in the study or influence study outcomes.
• Alcohol dependence, or positive drug abuse screening.
• Contraindication or history of allergy to medications used during the study (e.g., tacrolimus, levodopa, etc.) or any of their components; allergy to the above drugs, other macrolide drugs; or allergic constitution (e.g., allergy to two or more drugs or foods).
• Women of childbearing age who have not undergone sterilization/are not postmenopausal/are unwilling to use medically recognized effective contraception for 2 years after study drug administration, and breastfeeding women; men who have not undergone sterilization/are unwilling to use medically recognized effective contraception for 2 years after study drug administration.
• Receipt of electroconvulsive therapy within 30 days prior to administration.
• Currently participating in another clinical trial, or having participated in another clinical study and received interventional treatment within 3 months prior to administration.
• Severe dyskinesia in both medication "on" and "off" states.
• Serious illness, or poor compliance as judged by the investigator, or any other condition that the investigator believes may jeopardize subject safety or affect study evaluation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of USTC — Хэфэй

Идентификаторы

NCT: NCT07550374 · NouvNeu001-05

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗