Amyotrophic Lateral SclerosisPhase 2CORTEX-ALSNCT07834450
Efficacy and Safety of Cyclophosphamide in Amyotrophic Lateral Sclerosis
A Phase 2 study testing Cyclophosphamide and Riluzole in people with Amyotrophic Lateral Sclerosis, run by Huashan Hospital.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Cyclophosphamide and Riluzole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2026to 30 Sep 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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)
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?
Read more
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
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Cyclophosphamide, Riluzole
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
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.
RiluzoleDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Cyclophosphamide Plus Standard Treatment | Experimental | Not described Receives: Drug: Cyclophosphamide; Drug: Riluzole |
| Standard Treatment Alone | Active comparator | Not described Receives: Drug: Riluzole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score at 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.
Measured: Baseline to Week 48
Secondary outcomes (9)
Change From Baseline in Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) Score at Week 48
The Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) is a 28-item patient-reported scale used to assess overall disability in participants with amyotrophic lateral sclerosis. Each item is scored from 0 to 2, yielding a raw total score ranging from 0 to 56. The raw score is converted to a linearly weighted normed ROADS score ranging from 0 to 120, with higher scores indicating better functional status and lower scores indicating greater disability. The outcome measure is the change in the normed ROADS score from baseline to Week 48, calculated as the Week 48 score minus the baseline score. A more negative change indicates greater functional decline.
Measured: Baseline to Week 48
Change From Baseline in Dominant Hand Grip Strength at Week 48
Measured: Baseline to Week 48
Change From Baseline in Percent-Predicted Forced Vital Capacity (FVC) at Week 48
Forced vital capacity (FVC) will be measured using standardized pulmonary function testing procedures and expressed as a percentage of the predicted value based on appropriate reference equations. The outcome measure is the change in percent-predicted FVC from baseline to Week 48, calculated as the Week 48 value minus the baseline value. A greater decrease indicates greater deterioration in respiratory function.
Measured: Baseline to Week 48
Change From Baseline in Neurofilament Light Chain (NfL) Levels at Week 48
Measured: Baseline to Week 48
Change From Baseline in Compound Muscle Action Potential (CMAP) Amplitude at Week 48
Compound muscle action potential (CMAP) amplitude will be assessed using standardized motor nerve conduction studies. CMAP amplitude will be measured in millivolts (mV). The outcome measure is the change in CMAP amplitude from baseline to Week 48, calculated as the Week 48 value minus the baseline value. A greater reduction in CMAP amplitude indicates greater loss of functional motor axons.
Measured: Baseline to Week 48
Change From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) Score at Week 48
Measured: Baseline to Week 48
Time to Death, Enteral Feeding, or Permanent Assisted Ventilation
Measured: Randomization through Week 48
Change From Baseline in Percent-Predicted Slow Vital Capacity (SVC) at Week 48
Slow vital capacity (SVC) will be measured using standardized pulmonary function testing procedures and expressed as a percentage of the predicted value based on appropriate reference equations. The outcome measure is the change in percent-predicted SVC from baseline to Week 48, calculated as the Week 48 value minus the baseline value. A greater decrease indicates greater deterioration in respiratory function.
Measured: Baseline to Week 48
Change From Baseline in Motor Evoked Potential (MEP) Amplitude at Week 48
Motor evoked potential (MEP) amplitude will be assessed using standardized transcranial magnetic stimulation and neurophysiological recording procedures. MEP amplitude will be measured in millivolts (mV). The outcome measure is the change in MEP amplitude from baseline to Week 48, calculated as the Week 48 value minus the baseline value.
Measured: Baseline to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2026
- Study start1 Oct 2026 (estimated)
- Primary completion30 Oct 2028 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Huashan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xiangjun Chen, Huashan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07834450
- Sponsor's protocol ID
- KY2026-998
- Acronym
- CORTEX-ALS
- Status last verified
- Sep 2026
- First submitted
- 11 Sep 2026
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No