ABBV-CLS-7262 is administered orally once per day for 24 weeks.

Matching placebo is administered orally once per day for 24 weeks.

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.

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

Change from baseline to Week 24 in the activities of daily living (ADL)/independence domain score as assessed by the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40). The ALSAQ-40, a patient-self reported outcome, consists of 40 questions that are used to measure the subjective well-being of participants, and each question is scored from 0 (never) to 5 (always or cannot do at all). The ADL/independence domain score is based on 10 out of the 40 questions, with a maximum ADL/independence domain score of 50 and minimum score of 0. Higher domain scores indicate a worse subjective well-being or less independence completing ADLs.

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 24visit 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.

Matching placebo is administered orally once per day for 24 weeks.

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 pre-baseline decline score is 48-Baseline ALSFRS-R divided by the number of months between onset of weakness due to ALS and the date of Baseline. A higher number indicates faster 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.

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.

Change from baseline to Week 24 in function as assessed by ALSFRS-R total score.

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 measured 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.

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. The rate of mortality was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times.

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.

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.

Change from baseline to Week 24 in the activities of daily living (ADL)/independence domain score as assessed by the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40). The ALSAQ-40, a patient-self reported outcome, consists of 40 questions that are used to measure the subjective well-being of participants, and each question is scored from 0 (never) to 5 (always or cannot do at all). The ADL/independence domain score is based on 10 out of the 40 questions, with a maximum ADL/independence domain score of 50 and minimum score of 0. Higher domain scores indicate a worse subjective well-being or less independence completing ADLs.

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 24visit 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.

ABBV-CLS-7262 is administered orally once per day for 24 weeks.

Matching placebo is administered orally once per day for 24 weeks.

Covariates: baseline (BL) use edaravone, riluzole, Relyvrio, BL log-trans. NfL, SVC, time since onset, pre-BL ALSFRS-R slope, interactions with visit

ABBV-CLS-7262 Dose 2 24-week change from baseline relative to placebo 24-week change from baseline.

Model adjusted for covariates including baseline (BL) use of edaravone, riluzole and Relyvrio, BL log-transformed NfL, and SVC, time since onset, pre-BL ALSFRS-R slope and interaction with visit.

Covariates: baseline (BL) use edaravone, riluzole, Relyvrio, BL log-trans. NfL, SVC, time since onset, pre-BL ALSFRS-R slope, interactions with visit

ABBV-CLS-7262 Dose 2 24-week change from baseline relative to placebo 24-week change from baseline.

Model adjusted for covariates including baseline (BL) use of edaravone, riluzole and Relyvrio, BL log-transformed NfL, and SVC, time since onset, pre-BL ALSFRS-R slope and interaction with visit.

Covariates: baseline (BL) use edaravone, riluzole, Relyvrio, BL log-trans. NfL, SVC, time since onset, pre-BL ALSFRS-R slope, interactions with visit

ABBV-CLS-7262 Dose 2 24-week change from baseline relative to placebo 24-week change from baseline.

Model adjusted for covariates including baseline (BL) use of edaravone, riluzole and Relyvrio, BL log-transformed NfL, and SVC, time since onset, pre-BL ALSFRS-R slope and interaction with visit.

Covariates: baseline (BL) use edaravone, riluzole, Relyvrio, BL log-trans. NfL, SVC, time since onset, pre-BL ALSFRS-R slope, interactions with visit

Least squares mean difference between ABBV-CLS-7262 Dose 2 24-week change from baseline and placebo 24-week change from baseline.

Model adjusted for covariates including baseline (BL) use of edaravone, riluzole and Relyvrio, BL log-transformed NfL, SVC, time since onset, pre-BL ALSFRS-R slope and interaction with visit.

Covariates: baseline (BL) use edaravone, riluzole, Relyvrio, BL log-trans. NfL, SVC, time since onset, pre-BL ALSFRS-R slope, interactions with visit

ABBV-CLS-7262 Dose 2 24-week change from baseline relative to placebo 24-week change from baseline.

Model adjusted for covariates including baseline (BL) use of edaravone, riluzole and Relyvrio, BL log-transformed NfL, and SVC, time since onset, pre-BL ALSFRS-R slope and interaction with visit.