Amyotrophic Lateral Sclerosis
Conditions
Interventions
SAD:NP001: Intrathecal Administration. Single Administration.
Three dose groups (1.0, 3.0, and 9.0 × 10^7 Treg cells).
*If the Safety Review Committee (SRC) determines that a predefined dose group me
MAD:NP001: Intrathecal Administration.
Repeated dosing in the Phase MAD: Once monthly for a total of 3 doses.
Dose selection will be based on data from the Phase MAD.
D1:D1 NP001: Intrathecal Administration.
Repeated dosing in the Phase IIa: Once monthly for a total of 3 doses.
Dose selection will be based on data from the Phase IIa.
NP001 Placebo: Intrathecal Admi
D29:D29 NP001: Intrathecal Administration.
Repeated dosing in the Phase IIa: Once monthly for a total of 3 doses.
Dose selection will be based on data from the Phase IIa.
NP001 Placebo: Intrathecal Ad
D57:D57 NP001: Intrathecal Administration.
Repeated dosing in the Phase IIa: Once monthly for a total of 3 doses.
Dose selection will be based on data from the Phase IIa.
NP001 Placebo: Intrathecal Ad
Sponsors
Beijing Tiantan Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
18 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 18 to 70 years (inclusive). 2.Diagnosis of sporadic or familial Amyotrophic Lateral Sclerosis (ALS) defined according to the Gold Coast Criteria (Shefner, 2020), and classified as laboratory-supported probable, probable, or definite ALS according to the World Federation of Neurology El Escorial criteria. 3.Disease duration (from first symptom onset to Screening Visit) = 1 year, as judged by the Investigator. 5.Respiratory function at Screening: %FVC >= 65% and absence of dyspnea (dyspnea is defined in this study as a cumulative score = 30 points (individual subjects with ALSFRS-R score 30 mL/min (calculated using the Cockcroft-Gault formula); 2)Serum total bilirubin = 1.0 × 10^9/L (no growth factor support [e.g., G-CSF] within 7 days prior to Screening laboratory test); 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 test). 9.Subjects have no contraindications for peripheral blood mononuclear cell (PBMC) collection (e.g., hematocrit = 12 consecutive months of amenorrhea without an alternative medical cause). 11.Written Informed Consent Form (ICF) must be obtained prior to performing any study-related procedures that are not part of standard medical care. Subjects must understand that they may withdraw consent at any time without affecting future medical care.
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria will be excluded from this study: 1.History of hypersensitivity to any component of the NP001 Cell Injection. 2.Presence of uncontrolled active infection at Screening. 3.Significant concurrent condition or illness that, in the Investigator's judgment, would place the subject at undue risk or interfere with the study, including but not limited to: 1)Documented history of pulmonary embolism within 6 months prior to signing the ICF. 2)Chronic Obstructive Pulmonary Disease (COPD) within 6 months prior to signing the ICF. 3)Known moderate or severe persistent asthma, history of asthma within the past 2 years, or any category of uncontrolled asthma at present (Note: Subjects with currently controlled intermittent asthma or controlled mild persistent asthma are permitted). Requiring supplemental oxygen to maintain adequate oxygen saturation. 4.Significant cardiovascular or cerebrovascular disease, including but not limited to the following occurring within 6 months prior to signing the ICF: 1)Unstable angina, cerebrovascular accident, or transient ischemic attack. 2)Severe arrhythmias. 3)Severe non-ischemic cardiomyopathy. 4)ECG evidence of active conduction system abnormalities. 5)Congestive heart failure (New York Heart Association Class III or IV). 6)Other cardiac conditions requiring mechanical support (e.g., pacemaker). 7)Hypertension uncontrolled to 5 mg/day (or equivalent dose of other corticosteroids) within 1 week prior to apheresis. 15.Intolerance to essential medical procedures, such as apheresis, intrathecal injection, blood sampling, etc. 16.Current use of antipsychotics, antiepileptics (except benzodiazepines, gabapentin, pregabalin), or Class Ia (e.g., flecainide) or Class III (e.g., amiodarone) antiarrhythmic agents. 17.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Types, severity, and incidence of adverse events (AEs) and serious adverse events (SAEs);Phase I only: Incidence and characteristics of dose-limiting toxicity (DLT).;Phase I only: Maximum tolerated dose (MTD) of NP001 Cell Injection.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Effect of NP001 Cell Injection on Disease Status: Change from Baseline in ALS Disease Activity Scores ([ALSFRS-R] and [ROADS]); Change from Baseline in Forced Vital Capacity (%FVC); Change from Baseline in Limb Strength; Change from Baseline in Hand Grip Strength; Change from Baseline in Gait Function.;Overall survival (OS);Immunological Parameters in Blood: Change from Baseline in counts of: Th2 cells, Th1 cells, Treg cells, CD4+ T cells, CD25+ T cells, CD127- T cells, and FoxP3+ T cells. Change from Baseline in serum inflammatory factors and NfL.;Immunological Parameters in Cerebrospinal Fluid (CSF): Change from Baseline in inflammatory factors and NfL . Change from Baseline in counts of: CD4+ T cells, CD25+ T cells, CD127- T cells, and FoxP3+ T cells.; | — |
Countries
China
Contacts
Public ContactYilong Wang
Beijing Tiantan Hospital, Capital Medical University
Outcome results
None listed