Multiple System Atrophy
Conditions
Interventions
SAD:NP001: Intrathecal re-infusion, single administration, with three dose cohorts (1.0, 3.0, and 9.0 × 10^7 regulatory T cells). If the Study Review Committee (SRC) determines that a pre-specified do
MAD:NP001: Intrathecal infusion. Multiple-ascending dose phase with repeated administration once monthly for a total of three doses. Dosage to be selected based on the single-ascending dose phase.
Expansion Phase - Treatment Group - MSA-C:NP001: Intrathecal infusion. The expansion phase with repeated administration once monthly for a total of three doses. Dosage to be selected based on the MAD
Expansion Phase - Placebo Group - MSA-C:NP001: Intrathecal re-infusion. During the double-blind phase of the expansion period, an equal volume of 0.9% saline (placebo) will be administered. During the
Expansion Phase - Treatment Group - MSA-P:NP001: Intrathecal infusion. The expansion phase with repeated administration once monthly for a total of three doses. Dosage to be selected based on the MAD
Expansion Phase - Placebo Group - MSA-P:NP001: Intrathecal re-infusion. During the double-blind phase of the expansion period, an equal volume of 0.9% saline (placebo) will be administered. During the
Sponsors
Beijing Tiantan Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
30 Years to 70 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible for enrollment in this study: 1. Male or female subjects aged 30 to 70 years (inclusive). 2. Patients diagnosed with MSA according to the International Movement Disorder Society (MDS) criteria and the Chinese expert consensus (2022 edition), including neuropathologically confirmed, clinically established, and clinically probable MSA. 3. Duration of MSA (from first symptom onset to screening visit) = 3 years, as judged by the investigator. 5. Inadequate control of current core MSA symptoms with existing therapies. 6. Able to walk at least 10 steps independently without assistance, with or without aids (such as a walker or cane). 7. Respiratory function at screening: %FVC >= 65%. 8. No use of antiparkinsonian medications within 14 days prior to the first dose and no plan to use during the study, or have been on a stable dose of antiparkinsonian medications for at least 4 weeks with the dose to remain unchanged during the study. 9. Subjects must have adequate organ function, meeting all of the following laboratory results: (1) Creatinine clearance > 30 mL/min (calculated by Cockcroft-Gault formula); (2) Serum total bilirubin = 1.0 × 10^9/L (no granulocyte colony-stimulating factor [G-CSF] or similar growth factor support within 7 days prior to screening laboratory tests); (6) Lymphocyte count >= 0.3 × 10^9/L; (7) Platelet count >= 50 × 10^9/L (no platelet transfusion within 7 days prior to screening laboratory tests). 10. No contraindications to peripheral blood mononuclear cell collection (e.g., hematocrit = 12 consecutive months without other medical causes). 12. Before performing any study-related procedures that are not part of standard medical care, a signed informed consent form (ICF) must be obtained. Subjects must understand that they may withdraw the ICF at any time without affecting future medical care.
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be excluded from the study: 1. Head MRI at screening shows evidence of other central nervous system lesions suggesting a diagnosis of neurodegenerative diseases other than MSA. 2. Head MRI at screening shows other significant pathological findings, including but not limited to: cerebral hemorrhage, acute cerebral infarction, aneurysm, vascular malformation, infectious lesions, brain tumors, or other space-occupying lesions (meningiomas or arachnoid cysts with a maximum diameter =3 on Unified Multiple System Atrophy Rating Scale (UMSARS) Part I, Item 1; (2) Swallowing impairment as determined by a score of >=3 on UMSARS Part I, Item 2; (3) Walking impairment as determined by a score of >=3 on UMSARS Part I, Item 7; (4) Experiencing falls more than once per week as determined by a score of >=3 on UMSARS Part I, Item 8. 4. History of allergy to any component of the NP001 cell injection. 5. Presence of uncontrolled active infection at screening. 6. Presence of severe concurrent conditions or diseases that, in the investigator's judgment, would place the subject at undue risk or interfere with the study, including but not limited to: (1) History of pulmonary embolism documented within 6 months prior to signing the ICF; (2) History of chronic obstructive pulmonary disease (COPD) within 6 months prior to signing the ICF; (3) Known moderate or severe persistent asthma, or history of asthma within the past 2 years, or currently having uncontrolled asthma of any classification (Note: subjects with currently controlled intermittent or mild persistent asthma are allowed to participate). Requires supplemental oxygen to maintain adequate blood oxygen saturation. 7. Severe cardiovascular or cerebrovascular disease, including but not limited to any of the following within 6 months prior to signing the ICF: (1) Unstable angina, cerebrovascular accident, or transient ischemic attack; (2) Severe arrhythmia; (3) Severe non-ischemic cardiomyopathy; (4) Electrocardiographic evidence of active conduction system abnormalities; (5) Congestive heart failure (New York Heart Association Class III or IV); (6) Other cardiac diseases requiring mechanical support (e.g., pacemaker); (7) Hypertension that cannot be controlled to the following range (systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg) with <=2 antihypertensive medications; (8) Hypotension that remains below the normal range (systolic blood pressure <90 mmHg or diastolic blood pressure <60 mmHg) despite treatment; (9) Subjects with a history of coronary artery bypass grafting or angioplasty will undergo cardiology evaluation and be considered by the investigator on a case-by-case basis. 8. Subjects with systemic diseases judged by the investigator as unstable, including but not limited to severe hepatic, renal, respiratory, or metabolic diseases requiring pharmacologic treatment. 9. Screening serology tests positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis E virus (HEV), hepatitis A virus (HAV), or human T-lymphotropic virus (HTLV), indicating infection. 10. Pregnant or breastfeeding subjects. 11. Treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Type, severity, and incidence of adverse events (AEs) and serious adverse events (SAEs), including clinically significant changes in vital signs, physical examination, 12-lead ECG, and laboratory tests (complete blood count, blood biochemistry, coagulation function, urinalysis) following the administration of NP001 cell injection.;Incidence and characteristics of dose-limiting toxicities (DLTs).;Maximum tolerated dose (MTD) of NP001 cell injection.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Effect of NP001 cell injection on disease status: Changes from baseline in UMSARS, MoCA, %FVC, ATLIS, handgrip strength, gait function, COMPASS, 3T MRI imaging characteristics, and cerebral dopamine metabolic activity.;Overall Survival (OS);Immune system parameters in blood: Changes from baseline in the counts of Th2, Th1, and Treg cells; and changes in serum inflammatory cytokines and levels of NfL, GFAP, and TREM-2.;Immune system parameters in cerebrospinal fluid: Changes from baseline in the count of Treg cells; and changes in inflammatory cytokines and levels of NfL, GFAP, and TREM-2.; | — |
Countries
China
Contacts
Public ContactYilong Wang
Beijing Tiantan Hospital, Capital Medical University
Outcome results
None listed