HEALEY ALS Platform Trial - Regimen G DNL343

Change in disease severity as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) total score using a Bayesian repeated measures model that accounts for loss to follow-up due to mortality. Each of 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. Note that only participants who survived to their Week 24 visit contribute to the estimate.

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.

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.

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.

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