NCT07833618尚未招募2 期
A Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Dose-ranging Study to Evaluate the Efficacy and Safety of ALT001 in Patients With Amyotrophic Lateral Sclerosis
Darwin Origin (Hubei) Biopharmaceutical Co., Ltd.1 个研究点 分布在 1 个国家目标入组 150 人开始时间: 2026年9月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score
研究概览
简要总结
ALT001 is an allogeneic unrelated human umbilical cord mesenchymal stem cell-derived protein complex under investigation for the treatment of amyotrophic lateral sclerosis (ALS). This is a multicenter, randomized, double-blind, placebo-controlled, Phase 2 dose-ranging study in patients with ALS.
Approximately 150 participants will be randomized 1:1:1 to receive ALT001 1.0 μg/kg, ALT001 2.0 μg/kg, or matching placebo by intravenous infusion during the 24-week double-blind (DB) treatment period. During the OLE period, the active treatment groups will continue to receive their original dose under blinded conditions, whereas the placebo group will undergo re-randomization in a 1:1 ratio to receive 1.0 or 2.0 μg/kg ALT001.
The primary objective is to evaluate the dose-response relationship and efficacy of ALT001 at 1.0 and 2.0 μg/kg and to determine the recommended dose for subsequent studies. Secondary objectives include assessment of biomarkers related to efficacy and exploration of changes in cytokines, immune function, proteomics, and immunogenicity (anti-drug antibodies, ADA), as well as evaluation of the safety of ALT001.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants or their guardians must be able to understand the procedures and methods of this study, communicate adequately with the investigator, be willing to strictly comply with the clinical trial protocol to complete the study, and voluntarily sign a written informed consent form, or have informed consent signed by a legally authorized representative.
- •Age 18 to 75 years (inclusive of both boundaries), of either sex.
- •Diagnosis of definite or probable ALS according to the revised El Escorial criteria of the World Federation of Neurology for amyotrophic lateral sclerosis, including both familial and sporadic ALS patients.
- •Forced vital capacity (FVC) ≥ 50% of predicted at the screening visit.
- •Total ALSFRS-R score ≥ 30 and ≤ 40 prior to enrollment.
- •If receiving riluzole or edaravone treatment before enrollment, participants must have been on a stable dose for ≥ 30 days prior to Day 1 of this study, and must maintain that dose until the final study visit.
排除标准
- •Have other known diseases associated with motor neuron dysfunction that may confound or obscure the diagnosis of ALS.
- •History of alcohol dependence or drug abuse within 6 months prior to screening, judged by the investigator to be unsuitable for participation in this study.
- •Apparent cognitive impairment (MMSE scale: ≤19 for the illiterate group, ≤22 for the primary school group, and ≤26 for the junior high school and above group [>8 years of education]), or other unstable psychiatric disorders that the investigator considers unsuitable for participation (including suicidal intent, untreated major depression, etc.).
- •Continuous use of non-invasive ventilation (NIV), diaphragm pacing system, or invasive ventilation (tracheostomy) at screening.
- •Severe autoimmune diseases, myeloproliferative disorders, leukemia or lymphoma, malignant tumors, fractures, or severe scoliosis at screening, which the investigator considers would affect study evaluation.
- •Other severe and/or uncontrolled major organ or unstable systemic diseases, including but not limited to uncontrolled diabetes, unstable angina, cerebrovascular accident or transient ischemic attack (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), severe congestive heart failure, uncontrolled hypertension, uncontrolled active infection, severe hepatic, renal or other severe metabolic diseases, or severe gastrointestinal diseases.
- •Positive hepatitis B surface antigen (HBsAg) with HBV-DNA > upper limit of normal (if HBsAg is negative, HBV-DNA testing is not required); positive hepatitis C virus (HCV) antibody with HCV-RNA > upper limit of normal (if anti-HCV is negative, HCV-RNA testing is not required); positive human immunodeficiency virus (HIV) antibody; or positive Treponema pallidum test.
- •Pregnant or lactating women, and those planning to conceive during the medication period or within 3 months after stopping the medication.
- •Participated in another interventional clinical study within 4 weeks prior to this study; received stem cell or exosome therapy within 1 year, or previously received ASO drug treatment or gene therapy.
- •Judged by the investigator to be unsuitable for participation in this study (e.g., significantly clinically significant abnormalities in physical examination or laboratory tests).
研究组 & 干预措施
ALT001 1.0 μg/kg
Experimental
干预措施: ALT001 1.0 μg/kg (Drug)
ALT001 2.0 μg/kg
Experimental
干预措施: ALT001 2.0 μg/kg (Drug)
Placebo
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score
时间窗: Baseline to Week 24 (Week0, Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24 after randomization)
The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is a validated 12-item clinician-reported scale. Total score ranges from 0 to 48, with higher scores indicating better function and lower scores indicating greater functional impairment. A higher (less negative) change from baseline indicates less functional decline.
次要结局
- ALSFRS-R slope from baseline to Week 24 (double-blind period)(Baseline to Week 24(Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24 after randomization))
- ALSFRS-R slope from baseline to Week 48 (overall study period)(Overall study period：Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24, Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization(48 weeks))
- ALSFRS-R slope from Week 25 to Week 48 (open-label extension period)(Week 25 to Week 48 (Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization))
- Assessment of Combined Assessment of Function and Survival (CAFS)(Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24, Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization(48 weeks))
- Assessment of ventilator-free survival (VAFS)(Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24, Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization(48 weeks))
- Change from baseline in forced vital capacity (FVC) /slow vital capacity (SVC) percent predictedpercent predicted(Baseline to Week 48 (Week 0，Week 13，Week 24, Week25，Week37，Week48))
- Concentration of cytokines in serum (IFN-γ, IL-10, IL-13, IL-1β, IL-2, IL-4, IL-5, IL-6, GRO-α, TNF-α, IL-2)(Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.)
- Change from baseline in ALS Functional Staging System stage(Baseline to Week 48(Week 0，Week 13，Week 24, Week25，Week37，Week48 ))
- Change from baseline in ALSAQ-40 total score(Baseline to Week 48 (Week 0，Week 1, Week 13，Week 24, Week25，Week37，Week48))
- Change from baseline in ROADS total score(Baseline to Week 48 (Week 0，Week 1, Week 13，Week 24, Week25，Week37，Week48))
- Change from baseline in modified Ashworth scale score(Baseline to Week 48 (Week 0, Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24, Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization))
- Change from baseline in grip strength (kg)(Baseline to Week 48 (Week 0，Week 13，Week 24, Week25，Week37，Week48 ))
- Change from baseline in muscle strength (MRC sum score)(Baseline to Week 48 (Week 0，Week 13，Week 24, Week25，Week37，Week48 ))
- Concentration of neurofilament light chain (NfL) in plasma(Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24, Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization(48 weeks))
- Concentration of TAR DNA-binding protein 43 (TDP-43) in plasma(Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.)
- Concentration of superoxide dismutase 1 (SOD1) in plasma(Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.)
- Concentration of immunoglobulins in serum (IgG, IgM, IgA)(Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.)
- Number and percentage of T-cell subsets in blood (CD3+CD4+, CD3+CD8+, CD28+, CD16+)(Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.)
- Plasma proteomics profile(Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.)
- Incidence of treatment-emergent anti-drug antibodies (ADA)(Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.)
- Incidence of adverse events (AEs) and serious adverse events (SAEs)(From informed consent through 28 days after last dose)
研究者
研究点 (1)
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