NCT07834450尚未招募2 期
Efficacy and Safety of Cyclophosphamide in Amyotrophic Lateral Sclerosis: A Multicenter, Open-Label, Randomized, Parallel-Controlled Trial With Blinded Endpoint Assessment (CORTEX-ALS)
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
- 入组人数
- 60
- 主要终点
- Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score at Week 48
研究概览
简要总结
The goal of this clinical trial is to learn whether cyclophosphamide (CTX) combined with standard treatment can slow disease progression in adults with amyotrophic lateral sclerosis (ALS). It will also evaluate the safety and tolerability of CTX. The main questions it aims to answer are:
- Does CTX combined with standard treatment reduce the decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores over 48 weeks compared with standard treatment alone?
- What medical problems and side effects do participants have while receiving CTX?
- Are markers of neuroinflammation and immune activity, including TSPO-PET, neurofilament light chain (NfL), upper motor neuron burden, electrophysiological measures, immune cell profiles, and autoantibodies, associated with treatment response?
Researchers will compare CTX combined with standard treatment with standard treatment alone to see whether CTX can slow the progression of ALS.
Participants will:
- Be randomly assigned to receive CTX plus standard treatment or standard treatment alone
- Receive CTX treatment for up to 36 weeks if assigned to the CTX group
- Visit the study center regularly for clinical assessments, blood tests, lung function tests, electrophysiological tests, and other safety evaluations
- Complete assessments of physical function, muscle strength, respiratory function, and quality of life
- Undergo biomarker assessments, including TSPO-PET imaging and NfL testing
- Be followed for 48 weeks during the main study period and for up to 96 weeks for long-term outcomes and safety
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
- Triple (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
- •Age 18 to 75 years.
- •Diagnosis of amyotrophic lateral sclerosis (ALS) according to the 2020 revised Gold Coast diagnostic criteria, confirmed by an ALS specialist at a participating study center.
- •A decline of 1 to 4 points in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) during the 12-week observation period before randomization.
- •Time from symptom onset to randomization ≤2 years.
- •Positive TSPO-PET confirmed by the central imaging core laboratory.
- •Each ALSFRS-R item score ≥2 at baseline; the dyspnea, orthopnea, and respiratory insufficiency items must each have a score of
- •Baseline forced vital capacity (FVC) ≥70% of the predicted value.
- •Willing and able to comply with study treatment and follow-up procedures and provide written informed consent, including informed consent for off-label use of cyclophosphamide.
排除标准
- •Presence of an ALS mimic or another condition that better explains the clinical presentation, including multifocal motor neuropathy, motor-predominant chronic inflammatory demyelinating polyneuropathy, cervical spinal cord compression, Kennedy disease, hereditary spastic paraplegia, myasthenia gravis, inclusion body myositis, or metabolic, infectious, or paraneoplastic disorders.
- •Motor conduction block or clinically significant sensory nerve conduction abnormalities on nerve conduction studies.
- •Systemic autoimmune disease, such as systemic lupus erythematosus, rheumatoid arthritis, or Sjögren syndrome, requiring systemic immunosuppressive therapy.
- •Familial ALS, or a defined genetic ALS subtype such as SOD1-associated ALS currently receiving gene-targeted therapy or participating in another investigational drug trial.
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the upper limit of normal, or serum creatinine above the upper limit of normal.
- •Active infection, or uncontrolled hepatitis B virus infection, hepatitis C virus infection, human immunodeficiency virus infection, or active tuberculosis identified during screening.
- •White blood cell count <3.5 × 10^9/L, absolute neutrophil count <1.5 × 10^9/L, platelet count <100 × 10^9/L, or hemoglobin <90 g/L.
- •Severe concomitant neurological, cardiovascular, pulmonary, renal, hematologic, endocrine, or psychiatric disease that, in the investigator's judgment, may interfere with study participation or safety.
- •Suspected or confirmed history of alcohol or drug abuse.
- •Pregnancy or breastfeeding, or unwillingness of participants of reproductive potential to use effective contraception.
- •Known hypersensitivity to cyclophosphamide.
- •Participation in another interventional clinical trial within 3 months before screening.
- •Baseline imaging data of inadequate quality for analysis, including severe motion artifacts or incorrect acquisition parameters.
- •Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study, including poor adherence or a high likelihood of loss to follow-up.
研究组 & 干预措施
Standard Treatment Alone
Active Comparator
干预措施: Riluzole (Drug)
Cyclophosphamide Plus Standard Treatment
Experimental
干预措施: Riluzole (Drug)
Cyclophosphamide Plus Standard Treatment
Experimental
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score at Week 48
时间窗: Baseline to Week 48
The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is a 12-item scale used to assess functional impairment in participants with amyotrophic lateral sclerosis. Each item is scored from 0 to 4, yielding a total score ranging from 0 to 48. Higher total scores indicate better functional status, whereas lower scores indicate greater functional impairment. The outcome measure is the change in ALSFRS-R total score from baseline to Week 48, calculated as the Week 48 score minus the baseline score. A more negative change indicates greater functional decline.
次要结局
- Change From Baseline in Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) Score at Week 48(Baseline to Week 48)
- Change From Baseline in Dominant Hand Grip Strength at Week 48(Baseline to Week 48)
- Change From Baseline in Percent-Predicted Forced Vital Capacity (FVC) at Week 48(Baseline to Week 48)
- Change From Baseline in Neurofilament Light Chain (NfL) Levels at Week 48(Baseline to Week 48)
- Change From Baseline in Compound Muscle Action Potential (CMAP) Amplitude at Week 48(Baseline to Week 48)
- Change From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) Score at Week 48(Baseline to Week 48)
- Time to Death, Enteral Feeding, or Permanent Assisted Ventilation(Randomization through Week 48)
- Change From Baseline in Percent-Predicted Slow Vital Capacity (SVC) at Week 48(Baseline to Week 48)
- Change From Baseline in Motor Evoked Potential (MEP) Amplitude at Week 48(Baseline to Week 48)
研究者
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