Change in respiratory function over time as assessed by slow vital capacity (SVC)

Change in upper limb muscle strength over time as measured isometrically using hand-held dynamometry and grip strength, calculated as the average percent change from baseline of the following muscles/maneuvers: shoulder flexion, elbow flexion, elbow extension, wrist extension, abductor pollicis brevis contraction, abductor digiti minimi contraction, first dorsal interosseous contraction, and grip strength. Note that only those with measurable strength at baseline were included.

The number of participants who died or met the criterion for a death equivalent from the date of their baseline visit to the end of the Week 24 visit window (generally 175 days after baseline). The death equivalent criterion is use of permanent assisted ventilation (PAV) for more than 22 hours per day for more than 7 days in a row.

The number of participants who died from the date of their baseline visit to the end of the Week 24 visit window (generally 175 days after baseline).

Change in log-transformed serum neurofilament light protein (NfL) concentration from baseline to Week 24

Total of all reporting groups

The El Escorial Criteria are a set of guidelines used to diagnose ALS based on clinical signs of upper motor neuron and lower motor neuron dysfunction.

The ALS Functional Rating Score-Revised (ALSFRS-R) measures 12 aspects of physical function. Each of the 12 questions assessing distinct functional ability is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Participants with higher scores have more physical function.

The decline score is 48-Baseline is divided by the number of months between onset of weakness due to ALS and the date of Baseline. A higher number indicates greater decline.

Slow vital capacity is an assessment of breathing function. The total amount of air that can be exhaled is measured. A higher slow vital capacity indicates better breathing function.

Number analyzed in row differs from overall number due to missing data.

The King's ALS Clinical Staging System is a 4-level ordinal scale with the first three levels indicating the number (1, 2, or 3) of distinct central nervous system regions (bulbar, upper limb, and lower limb) with neuromuscular dysfunction. Level 4a indicates nutritional failure and level 4b indicates respiratory failure. Higher scores indicate a worse disease state.

Number analyzed in row differs from overall number due to missing data.

Number analyzed in row differs from overall number due to missing data.

Change in ALSFRS-R total score over time. Each type of function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Participants with higher scores have more physical function.

Outcome measure data was analyzed using the Efficacy Concurrent-controls Set (ECC), which included concurrent shared placebos from other regimens if randomized within 180 days of the first and last randomization for the applicable regimen, excluding any shared placebos also include in the focal regimen, as pre-specified in the Regimen Statistical Analysis Plan. Regimen F (NCT#05740813) and Regimen G (NCT#05842941) contributed placebo participants into the shared placebo cohort used for analysis.

Combined assessment of function and survival (CAFS) ranks participants' clinical outcomes based on survival time and change in the functional score. Each participant's outcome is compared to every other participant's outcome, assigned a score, and the summed scores are ranked. The mean rank score for each treatment group can then be calculated. A higher mean CAFS rank score indicates a better group outcome. The survival outcome is death or death-equivalent, where a participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row. The functional outcome is the ALS Functional Rating Scale-Revised (ALSFRS-R) score with a maximum total score of 48 and a minimum total score of 0. Participants with higher scores have more physical function.

Outcome measure data was analyzed using the Efficacy Concurrent-controls Set (ECC), which included concurrent shared placebos from other regimens if randomized within 180 days of the first and last randomization for the applicable regimen, excluding any shared placebos also include in the focal regimen, as pre-specified in the Regimen Statistical Analysis Plan. Regimen F (NCT#05740813) and Regimen G (NCT#05842941) contributed placebo participants into the shared placebo cohort used for analysis.

Change in respiratory function over time as assessed by slow vital capacity (SVC)

Outcome measure data was analyzed using the Efficacy Concurrent-controls Set (ECC), which included concurrent shared placebos from other regimens if randomized within 180 days of the first and last randomization for the applicable regimen, excluding any shared placebos also include in the focal regimen, as pre-specified in the Regimen Statistical Analysis Plan. Regimen F (NCT#05740813) and Regimen G (NCT#05842941) contributed placebo participants into the shared placebo cohort used for analysis.

Change in upper limb muscle strength over time as measured isometrically using hand-held dynamometry and grip strength, calculated as the average percent change from baseline of the following muscles/maneuvers: shoulder flexion, elbow flexion, elbow extension, wrist extension, abductor pollicis brevis contraction, abductor digiti minimi contraction, first dorsal interosseous contraction, and grip strength. Note that only those with measurable strength at baseline were included.

Outcome measure data was analyzed using the Efficacy Concurrent-controls Set (ECC), which included concurrent shared placebos from other regimens if randomized within 180 days of the first and last randomization for the applicable regimen, excluding any shared placebos also include in the focal regimen, as pre-specified in the Regimen Statistical Analysis Plan. Regimen F (NCT#05740813) and Regimen G (NCT#05842941) contributed placebo participants into the shared placebo cohort used for analysis.

The Mortality Rate, presented as mean deaths per month, was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times. Mortality is defined as death or death equivalent. A participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row.

Outcome measure data was analyzed using the Efficacy Concurrent-controls Set (ECC), which included concurrent shared placebos from other regimens if randomized within 180 days of the first and last randomization for the applicable regimen, excluding any shared placebos also include in the focal regimen, as pre-specified in the Regimen Statistical Analysis Plan. Regimen F (NCT#05740813) and Regimen G (NCT#05842941) contributed placebo participants into the shared placebo cohort used for analysis.

The number of participants who died or met the criterion for a death equivalent from the date of their baseline visit to the end of the Week 24 visit window (generally 175 days after baseline). The death equivalent criterion is use of permanent assisted ventilation (PAV) for more than 22 hours per day for more than 7 days in a row.

Outcome measure data was analyzed using the Efficacy Concurrent-controls Set (ECC), which included concurrent shared placebos from other regimens if randomized within 180 days of the first and last randomization for the applicable regimen, excluding any shared placebos also include in the focal regimen, as pre-specified in the Regimen Statistical Analysis Plan. Regimen F (NCT#05740813) and Regimen G (NCT#05842941) contributed placebo participants into the shared placebo cohort used for analysis.

The number of participants who died from the date of their baseline visit to the end of the Week 24 visit window (generally 175 days after baseline).

Outcome measure data was analyzed using the Efficacy Concurrent-controls Set (ECC), which included concurrent shared placebos from other regimens if randomized within 180 days of the first and last randomization for the applicable regimen, excluding any shared placebos also include in the focal regimen, as pre-specified in the Regimen Statistical Analysis Plan. Regimen F (NCT#05740813) and Regimen G (NCT#05842941) contributed placebo participants into the shared placebo cohort used for analysis.

Change in log-transformed serum neurofilament light protein (NfL) concentration from baseline to Week 24

Outcome measure data was analyzed using the Efficacy Concurrent-controls Set (ECC), which included concurrent shared placebos from other regimens if randomized within 180 days of the first and last randomization for the applicable regimen, excluding any shared placebos also include in the focal regimen, as pre-specified in the Regimen Statistical Analysis Plan. Regimen F (NCT#05740813) and Regimen G (NCT#05842941) contributed placebo participants into the shared placebo cohort used for analysis.

Matching Placebo is administered orally once a day for 24 weeks.