Efficacy and Safety of Cyclophosphamide in Amyotrophic Lateral Sclerosis
ConditionAmyotrophic Lateral Sclerosis
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorHuashan Hospital
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Cyclophosphamide
DrugCyclophosphamide 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
DrugRiluzole 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.
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Cyclophosphamide Plus Standard TreatmentExperimental treatment 2 interventions
Group B: Standard Treatment AloneActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Baseline to Week 48Secondary outcomes
1
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.
Time frame
Baseline to Week 482
Change From Baseline in Dominant Hand Grip Strength at Week 48
Time frame
Baseline to Week 483
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.
Time frame
Baseline to Week 484
Change From Baseline in Neurofilament Light Chain (NfL) Levels at Week 48
Time frame
Baseline to Week 48Other outcomes
1
Change From Baseline in ALSFRS-R Total Score at Week 96
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.
Time frame
Baseline to Week 962
Change From Baseline in Percent-Predicted Forced Vital Capacity (FVC) at Week 96
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 96, calculated as the Week 96 value minus the baseline value. A greater decrease indicates greater deterioration in respiratory function.
Time frame
Baseline to Week 963
Change From Baseline in King's College Clinical Staging System Stage Through Week 96
Disease progression will be assessed using the King's College Clinical Staging System for amyotrophic lateral sclerosis. The system classifies disease progression according to the number of central nervous system regions involved and the occurrence of nutritional or respiratory failure. Stages range from Stage 1 to Stage 4, with Stage 4 subdivided into Stage 4A (nutritional failure) and Stage 4B (respiratory failure). Higher stages indicate more advanced disease. Change in King's College Clinical Stage from baseline through Week 96 will be evaluated.
Time frame
Baseline through Week 964
Change From Baseline in Amyotrophic Lateral Sclerosis Milano-Torino Staging (ALS-MiToS) System Stage Through Week 96
Disease progression will be assessed using the Amyotrophic Lateral Sclerosis Milano-Torino Staging (ALS-MiToS) System, which is based on loss of independence in four functional domains derived from the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R): walking/self-care, swallowing, communicating, and breathing. Stages range from 0 to 5. Stage 0 indicates no loss of independence in any domain; Stages 1 through 4 indicate loss of independence in one to four domains, respectively; and Stage 5 indicates death. Higher stages indicate more advanced disease and greater loss of functional independence. Change in ALS-MiToS stage from baseline through Week 96 will be evaluated.
Time frame
Baseline through Week 96Locations
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Source ClinicalTrials.gov
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