Table 2 Secondary and exploratory outcomes

Clinical

 ALSFRS-R score (ALSFRS-R)

ALS Functional Rating Scale Revised consists of 12 questions, each scored out of 4 points. A total score is calculated by summing the scores from each question with a maximum score of 48 (better performance, i.e., absence of the measured symptoms of ALS) and a minimum score of 0 (worst performance)

 Survival time measured by death or respiratory insufficiency

Survival status is recorded at the end of study as well as respiratory insufficiency defined as tracheostomy or the use of non-invasive ventilation for ≥ 22 h per day for ≥ 10 consecutive days. Survival time is defined as the time elapsed between randomization and death from any cause and tracheostomy, whichever occurs first

 Forced vital capacity score (FVC)

The index of respiratory function expressed as a percentage of the expected value is used to indicate potential respiratory compromise

 Muscle force assessed by the Medical Research Council (MRC) scale

MRC score is a summation of the strength of 6 muscle groups tested on both sides ranging from 0 (paralysis) to 60 (normal strength)

Health-related quality of life

 Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40)

ALSAQ-40 score is a patient self-report health status PRO based on 40 questions specifically used to measure the subjective well-being of patients with ALS in a scale from 0 (best possible health status) to 100 (worst possible)

 EQ-5D scale score (EQ-5D-5L)

The 5-level EQ-5D version is a self- assessed health-related quality of life (HRQoL) questionnaires based on 5 questions ranging from 0 (worst health) to 100 (best health)

Biomarker

 Creatinine level

Plasma creatinine is a breakdown product of creatine phosphate and it is related to muscle mass, expressed in μmol/L or micromol/L

 Neurofilament level

Value of neurofilaments (light chain and phosphorylated heavy chain) in the CSF and serum resulting as a mean from triplicate measurements expressed in pg/ml

 MMP-9 expression

The expression of matrix metalloproteinase-9 in serum is a mean of at least two duplicates, expressed in pg/ml