Table 1 Description of primary, secondary, exploratory endpoints and analysis method

Primary

(1) Difference in joint rank scores between study Group 2 and control group at 12 months

(2) Difference in joint rank scores between study Group 1 and control group at 6 months

(1, 2) Analysis of covariance (ANCOVA) with adjustment of baseline ALSFRS-R score, baseline ALSFRS-R progression rate, and stratification factors

(1, 2) Generalized Gehan-Wilcoxon rank test for supportive analysis

Secondary

(1) Difference in joint rank scores between study Group 2 and control group at 6 months

(2) Change from baseline in ALSFRS-R score at 12 months (study Group 2 and control group)

(3) Change from baseline in ALSFRS-R score at 6 months (study Group 1 and control group)

(1, 2, 3) ANCOVA with adjustment of baseline ALSFRS-R score, baseline ALSFRS-R progression rate, and stratification factors

(4) Time-to-event at 12 months (study Group 2 and control group)

(5) Time-to-event at 6 months (study Group 1 and control group)

(4, 5) Stratified cox proportional hazards model with adjustment of baseline ALSFRS-R progression rate and stratification factors

Exploratory

(1) Comparison of the change from baseline in SVC score at 6 months (study Group 1 and control group) and 12 months (study Group 2 and control group)

(1, 3, 8, 10) ANCOVA with adjustment of the baseline value, baseline ALSFRS-R progression rate, and stratification factors

(2) Change from baseline in SVC score at 36 months

(3) Comparison of the change from baseline in muscular strength at 6 months (study Group 1 and control group) and 12 months (study Group 2 and control group)

(4) Change from baseline in muscular strength at 36 months

(5) Time-to-event at 36 months

(6) Comparison of the time-to-death at 6 months (study Group 1 and control group) and 12 months (study Group 2 and control group)

(7) Time-to-death at 36 months

(8) Comparison of the change from baseline in EQ-5D-5 L index value at 6 months (study Group 1 and control group) and 12 months (study Group 2 and control group)

(9) Change from baseline in EQ-5D-5 L index value at 36 months

(10) Comparison of the change from baseline in ALS Assessment Questionnaire (ALSAQ)-40 scores at 6 months (study Group 1 and control group) and 12 months (study Group 2 and control group)

(11) Change from baseline in ALSAQ-40 scores at 36 months

(12) Comparative analysis of cytokines in peripheral blood at baseline and individual points

(13) Comparative analysis of cytokines in cerebrospinal at baseline and individual points

(14) Analysis of regulatory T cell functions at baseline and individual points

(15) Comparative analysis of transcriptome at baseline and individual points

(2, 4, 5, 7, 9, 11) Summarized by treatment groups

(6) Stratified cox proportional hazards model with adjustment of baseline ALSFRS-R progression rate and stratification factors

(12, 13, 14) Repeated measures generalized estimating equations with an AR(1) correlation structure

(15) Standard transcriptome analysis pipeline