Can an old chemotherapy drug slow ALS? trial tests immune target

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * 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 4. * 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. Exclusion Criteria: * 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.