The CAFS scale is a combined endpoint ranking subjects' clinical outcomes based on ALS Functional Rating Scale-Revised (ALSFRS-R-described below) and survival time. For ALSFRS-R, 12 functions were rated on 5-point ordinal rating scales (0 to 4) with a total score range of 0-48 (sum of all 12 items); higher score indicated better functioning. For survival time, longer the subject survives indicated better outcome. Each subject's outcome was compared to every other subject outcome in trial in series of pairwise comparisons, summed scores (sum of comparisons [+1 {better}, 0 {tie}, -1 {worse}]) were ranked and ranged from 001-247 (number of subjects in modified [m]ITT population).Reported values are the least squares mean rank scores in each group for the composite endpoint. Higher rank indicated better outcome.

mITT set included all randomized subjects who received at least 1 dose of randomized treatment (pegcetacoplan or placebo) and who died or had a postbaseline assessment of endpoint that was used in CAFS. Only subjects with data collected at Week 52 are reported.

An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An SAE was any AE or suspected adverse reaction that, in the view of the investigator, resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital anomaly or birth defect. TEAEs were AEs that started on or after first dose of study drug or started before first dose of study drug but increased in severity on or after the first dose of study drug up to 56 days post last dose of study drug.

The safety set for RTP included all subjects who received at least 1 dose of study drug: pegcetacoplan or placebo.

An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An SAE was any AE or suspected adverse reaction that, in the view of the investigator, resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital anomaly or birth defect. TEAEs were AEs that started on or after first dose of study drug or started before first dose of study drug but increased in severity on or after the first dose of study drug up to 56 days post last dose of study drug.

The safety set for the OLP included only those subjects who received at least 1 dose of the open-label treatment.

The C-SSRS is a measure used to identify and assess individuals at risk for suicide and included "yes" or "no" responses for assessment of suicidal ideation (SI) and suicidal behavior (SB).C-SSRS SI items are classified on 5-item scale:1 (wish to be dead),2 (non-specific active suicidal thoughts),3 (active SI with any methods without intent to act),4 (active SI with some intent to act, without specific plan) and 5 (active SI with a specific plan and intent).C-SSRS SB items are classified on 5-item scale: 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), 4 (actual attempt [non-fatal]) and 5 (completed suicide). Numeric ratings were provided for SI (1 to 5) and SB (1 to 5) with 5 being more severe for each. Number of subjects with a response of 'yes' to SI only, SB only & SI and SB are reported. Baseline: last available, non-missing observation prior to first study drug administration.

The safety set for RTP included all subjects who received at least 1 dose of study drug: pegcetacoplan or placebo.

The C-SSRS is a measure used to identify and assess individuals at risk for suicide and included "yes" or "no" responses for assessment of SI and SB.C-SSRS SI items are classified on 5-item scale:1 (wish to be dead),2 (non-specific active suicidal thoughts),3 (active SI with any methods without intent to act),4 (active SI with some intent to act, without specific plan) and 5 (active SI with a specific plan and intent).C-SSRS SB items are classified on 5-item scale:1 (preparatory acts or behavior),2 (aborted attempt), 3 (interrupted attempt), 4 (actual attempt [non-fatal]) and 5 (completed suicide). Numeric ratings were provided for SI (1 to 5) and SB (1 to 5) with 5 being more severe for each. Number of subjects with a response of 'yes' to SI only, SB only & SI and SB are reported. Baseline: last available, non-missing observation prior to first study drug administration in OLP.

The safety set for the OLP included only those subjects who received at least 1 dose of the open-label treatment.

The ALSFRS-R included 12 items for assessment of functional status: speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing and hygiene, turning in bed and adjusting bed clothes, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency. Each item ranged from 0 (no ability) to 4 (normal ability). Individual item scores were summed to produce a total score between 0 (worst) and 48 (best) with higher scores meaning better outcome. Least squares mean is presented here. Baseline was defined as the last available, non-missing observation prior to first study drug administration.

The ITT set for RTP included all randomized subjects who received at least 1 dose of randomized treatment (pegcetacoplan or placebo). Only those subjects with data collected at Baseline and Week 52 are reported.

SVC is a pulmonary function test and predictor of functional loss in ALS. It was conducted at clinic visits with the clinic spirometer which reflected the maximum amount of air that could be exhaled slowly. %SVC is the actual volume exhaled in the first 1 second, divided by the normal value for that actual value for a person of that age, gender, height and weight. Baseline was defined as the last available, non-missing observation prior to first study drug administration.

The ITT set for RTP included all randomized subjects who received at least 1 dose of randomized treatment (pegcetacoplan or placebo). Only those subjects with data collected at baseline and Week 52 are reported.

Muscle strength was measured using handheld dynamometry (HHD) and assessed the following muscles: first dorsal interosseous, wrist extension, elbow extension, elbow flexion, shoulder flexion, knee extension, knee flexion, and ankle dorsiflexion, on both sides of the body. Baseline was defined as the last available, non-missing observation prior to first study drug administration.

The ITT set for RTP included all randomized subjects who received at least 1 dose of randomized treatment (pegcetacoplan or placebo). Only those subjects with data collected at baseline and Week 52 are reported.

Subjects with an event (that is, either death or permanent tracheostomy or permanent assisted ventilation) in RTP are reported.

The ITT set for RTP included all randomized subjects who received at least 1 dose of randomized treatment (pegcetacoplan or placebo).

The ALSAQ-40 was a 40-item validated questionnaire designed to assess health related quality of life (QoL) over the previous 2 weeks in subjects with ALS. It represented 5 dimensions of health status; each scored from 0 (never, or best) to 4 (always, or worst). 5 dimensions evaluated were: physical mobility (10 items: 1-10; possible score of 0-40); activities of daily living/independence (10 items: 11-20; possible score of 0-40); eating and drinking (3 items: 21-23; possible score of 0-12); communication (7 items: 24-30; possible score: 0-28) and emotional functioning (10 items: 31-40; possible score: 0-40). The total score 0 (no impairment) to 160 (severe impairment) was calculated by adding the 5 dimension scores; least squares mean is presented here. Higher scores indicated worse QoL.

The ITT set for RTP included all randomized subjects who received at least 1 dose of randomized treatment (pegcetacoplan or placebo). Only those subjects with data collected at baseline and Week 52 are reported.

The ALSFRS-R included 12 items for assessment of functional status: speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing and hygiene, turning in bed and adjusting bed clothes, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency. Each item ranged from 0 (no ability) to 4 (normal ability). Individual item scores were summed to produce a total score between 0 (worst) and 48 (best) with higher scores meaning better outcome. Mean is presented here. Baseline was defined as the last observed value for the efficacy assessment prior to taking the first dose of study drug in OLP.

The ITT set for OLP included all randomized subjects who received at least 1 dose of open label treatment. Only those subjects with data collected at specified timepoints are reported.

SVC is a pulmonary function test and predictor of functional loss in ALS. It was planned to be conducted at clinic visits with the clinic spirometer which reflected the maximum amount of air that could be exhaled slowly. %SVC is the actual volume exhaled in the first 1 second, divided by the normal value for that actual value for a person of that age, gender, height and weight. Baseline was defined as the last available, non-missing observation prior to first study drug administration.

Analysis was planned to be performed on the ITT population. Data was not collected for this outcome measure as the study was terminated early since it did not meet key secondary efficacy endpoints criteria.

Muscle strength was planned to be measured using HHD and assessed the following muscles: first dorsal interosseous, wrist extension, elbow extension, elbow flexion, shoulder flexion, knee extension, knee flexion, and ankle dorsiflexion, on both sides of the body. Baseline was defined as the last available, non-missing observation prior to first study drug administration.

Analysis was planned to be performed on the ITT population. Data was not collected for this outcome measure as the study was terminated early since it did not meet key secondary efficacy endpoints criteria.

Subjects with an event of death are reported. Subjects were planned to be assessed for permanent tracheostomy or permanent assisted ventilation in OLP; however, that data was not collected as study was terminated early.

The ITT set for OLP included all randomized subjects who received at least 1 dose of open label treatment.

The ALSAQ-40 was a 40-item validated questionnaire designed to assess health related QoL over the previous 2 weeks in subjects with ALS. It represented 5 dimensions of health status; each scored from 0 (never, or best) to 4 (always, or worst). 5 dimensions evaluated were: physical mobility (10 items: 1-10; possible score of 0-40); activities of daily living/independence (10 items: 11-20; possible score of 0-40); eating and drinking (3 items: 21-23; possible score of 0-12); communication (7 items: 24-30; possible score: 0-28) and emotional functioning (10 items: 31-40; possible score: 0-40). The total score 0 (no impairment) to 160 (severe impairment) was planned to be calculated by adding the 5 dimension scores. Higher scores would have indicated worse QoL.

Analysis was planned to be performed on the ITT population. Data was not collected for this outcome measure as the study was terminated early since it did not meet key secondary efficacy endpoints criteria.

Total number of subjects who died in the study are reported.

The ITT set for RTP included all randomized subjects who received at least 1 dose of randomized treatment (pegcetacoplan or placebo). The ITT set for OLP included all randomized subjects who received at least 1 dose of open label treatment.