Overview
- Official title
- Efficacy and Safety of Cyclophosphamide in Amyotrophic Lateral Sclerosis: A Multicenter, Open-Label, Randomized, Parallel-Controlled Trial With Blinded Endpoint Assessment (CORTEX-ALS)
- Brief title
- Efficacy and Safety of Cyclophosphamide in Amyotrophic Lateral Sclerosis
- Registration type
- ClinicalTrials.gov
- NCT number
- NCT07834450
- Status
- Not yet recruiting
- Study category
- Interventional, Drug trial, Biomarker, Genetic, Imaging
- Sponsor / center
- Huashan Hospital
- Research center
- Not stated in the official study record.
- Collaborators
- Not stated in the official study record.
- Study type
- Interventional study
- Phase
- Phase 2
- Enrollment
- 60
- Start date
- 10-01-2026
- Primary completion date
- 10-30-2028
- Estimated / actual completion date
- 09-30-2029
- Last source update
- 09-22-2026
What is being studied?
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:
1. 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?
2. What medical problems and side effects do participants have while receiving CTX?
3. 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:
1. Be randomly assigned to receive CTX plus standard treatment or standard treatment alone
2. Receive CTX treatment for up to 36 weeks if assigned to the CTX group
3. Visit the study center regularly for clinical assessments, blood tests, lung function tests, electrophysiological tests, and other safety evaluations
4. Complete assessments of physical function, muscle strength, respiratory function, and quality of life
5. Undergo biomarker assessments, including TSPO-PET imaging and NfL testing
6. Be followed for 48 weeks during the main study period and for up to 96 weeks for long-term outcomes and safety
Intervention(s)
Cyclophosphamide
Type: DRUG
Cyclophosphamide will be administered intravenously for 36 weeks in addition to standard treatment with riluzole. During the induction phase, participants will receive a total dose of 2.0 g over approximately 2 weeks in four divided infusions (400 mg, 600 mg, 400 mg, and 600 mg), with an interval of 1-2 days between infusions. During the maintenance phase, cyclophosphamide 1.0 g will be administered intravenously every 4 weeks through Week 36, for a planned cumulative dose of approximately 10.0 g. Hydration, mesna, and antiemetic treatment will be provided as appropriate. Dose delay, dose reduction, or permanent discontinuation will be permitted for treatment-related toxicity according to the study protocol.
Riluzole
Type: DRUG
Riluzole will be administered orally at a dose of 50 mg twice daily as standard treatment for amyotrophic lateral sclerosis. Participants should be receiving a stable dose before randomization and will continue treatment during the study unless dose modification or discontinuation is required for safety or tolerability reasons.
Who may be eligible?
This is a simplified summary. The official study team or research center determines eligibility.
- Population / disease status
- Familial / genetic ALS, Diagnosed ALS
- Diagnosis / conditions
- Amyotrophic Lateral Sclerosis
- Age
- 18 Years to 75 Years
- Disease duration
- ≤ 24 months
- Respiratory criteria
- The official eligibility criteria include language relevant to this topic; review the full criteria below.
- ALSFRS-R criteria
- The official eligibility criteria include language relevant to this topic; review the full criteria below.
- Genetic criteria
- The official eligibility criteria include language relevant to this topic; review the full criteria below.
- Medication requirements
- Not stated in the official study record.
Major inclusion and exclusion criteria from the official record
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.
