Efficacy and Safety of Cyclophosphamide in Amyotrophic Lateral Sclerosis

NCT07834450 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: KY2026-998
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief 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. 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. 2.What medical problems and side effects do participants have while receiving CTX?
3. 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?
4. 4.Be randomly assigned to receive CTX plus standard treatment or standard treatment alone
5. 5.Receive CTX treatment for up to 36 weeks if assigned to the CTX group
6. 6.Visit the study center regularly for clinical assessments, blood tests, lung function tests, electrophysiological tests, and other safety evaluations
7. 7.Complete assessments of physical function, muscle strength, respiratory function, and quality of life
8. 8.Undergo biomarker assessments, including TSPO-PET imaging and NfL testing
9. 9.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

Outcome Measures

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.

  Baseline to Week 48

Secondary Outcomes (9)

• 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

Other Outcomes (6)

• Change From Baseline in ALSFRS-R Total Score at Week 96

  Baseline to Week 96

• Change From Baseline in Percent-Predicted Forced Vital Capacity (FVC) at Week 96

  Baseline to Week 96

• Change From Baseline in King's College Clinical Staging System Stage Through Week 96

  Baseline through Week 96

Study Arms (2)

Cyclophosphamide Plus Standard Treatment

EXPERIMENTAL

Drug: Cyclophosphamide; Drug: Riluzole

Standard Treatment Alone

ACTIVE COMPARATOR

Drug: Riluzole

Interventions

Cyclophosphamide 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.

Cyclophosphamide Plus Standard Treatment

Riluzole 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.

Cyclophosphamide Plus Standard Treatment; Standard Treatment Alone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Huashan Hospital: lead

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Cyclophosphamide; Riluzole

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Xiangjun Chen, M.D. & Ph.D.

CONTACT

+8618221382327; Xiangjchen@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 11, 2026
• First Posted: September 22, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 30, 2028
• Study Completion (Estimated): September 30, 2029
• Last Updated: September 22, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share