MERIDIAN: A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Adults With Amyotrophic Lateral Sclerosis (ALS)

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04579666

Enrollment

249

Registered

2020-10-08

Start date

2020-09-30

Completion date

2023-07-13

Last updated

2025-04-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Amyotrophic Lateral Sclerosis, Motor Neuron Disease

Keywords

Amyotrophic Lateral Sclerosis, ALS, Motor Neuron Disease, APL-2, APL2, Pegcetacoplan

Brief summary

This is a 24-month, Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of pegcetacoplan in subjects with amyotrophic lateral sclerosis (ALS)

Interventions

DRUGPegcetacoplan (APL-2)

Complement (C3) Inhibitor

OTHERPlacebo

Sterile solution of equal volume to active arm

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* At least 18 years of age * Sporadic ALS diagnosed as definite, probable, or laboratory-supported probable as defined by the revised El Escorial criteria * Slow vital capacity (SVC) ≥60% of the predicted value at screening * Onset of ALS symptoms within 72 weeks (18 months) prior to screening * Total ALSFRS-R score of ≥30 at screening * Have vaccination within 5 years against Streptococcus pneumoniae, Neisseria meningitidis (types A, C, W, Y, and B), and Haemophilus influenzae (type B) or agree to receive vaccination

Exclusion criteria

* Confirmed or suspected other causes of neuromuscular weakness * Diagnosed with another neurodegenerative disease (examples include Parkinson's disease and Huntington's disease) * Significant pulmonary disorder not attributed to ALS (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension) * If taking riluzole, participant must be on a stable dose for 30 days prior to the start of the screening period. Use of riluzole is not required for participation. * If taking edaravone, participant must be on a stable dose for 60 days prior to the start of the screening period. Use of edaravone is not required for participation. * Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days or within 5-half lives of the treatment (whichever is longer) prior to the start of the screening period or during study participation * Use of any other complement inhibitor within 30 days or within 5-half lives of the treatment (whichever is longer) prior to the start of the screening period or during study participation

Design outcomes

Primary

Measure	Time frame	Description
RTP: Combined Assessment of Function and Survival (CAFS) Rank Score (Joint-Rank Score) at Week 52	Week 52	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.
RTP: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	From first dose of study drug (Day 1) up to 56 days post last dose of study drug, approximately 60 weeks	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.
OLP: Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events	From first dose of study drug (Week 52) up to 56 days post last dose of study drug, approximately 60 weeks	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.
RTP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) up to Week 52	Baseline (Day 1) up to Week 52	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.
OLP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale up to Week 104	From Baseline (Week 52) up to Week 104	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.

Secondary

Measure	Time frame	Description
OLP: Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Score at Week 104	Baseline (Week 52) and Week 104	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.
OLP: Change From Baseline in Percent Predicted Slow Vital Capacity at Week 104	Baseline (Week 52) and Week 104	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.
OLP: Change From Baseline in Muscle Strength at Week 104	Baseline (Week 52) and Week 104	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.
RTP: Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score at Week 52	Baseline (Day 1) and Week 52	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.
OLP: Change From Baseline in ALS Assessment Questionnaire-40 at Week 104	Baseline (Week 52) and Week 104	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.
Number of Subjects With an Event of Death During the Study	RTP: Baseline (Day 1) up to Week 52; OLP: Baseline (Week 52) up to Week 104	Total number of subjects who died in the study are reported.
OLP: Number of Subjects With an Event of Death or Permanent Tracheostomy or Permanent Assisted Ventilation at Week 104	Baseline (Week 52) and Week 104	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.
RTP: Change From Baseline in Percent Predicted Slow Vital Capacity (%SVC) at Week 52	Baseline (Day 1) and Week 52	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.
RTP: Change From Baseline in Muscle Strength at Week 52	Baseline (Day 1) and Week 52	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.
RTP: Number of Subjects With an Event of Death or Permanent Tracheostomy or Permanent Assisted Ventilation at Week 52	Baseline (Day 1) up to Week 52	Subjects with an event (that is, either death or permanent tracheostomy or permanent assisted ventilation) in RTP are reported.
RTP: Change From Baseline in ALS Assessment Questionnaire (ALSAQ)-40 at Week 52	Baseline (Day 1) and Week 52	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.

Countries

Australia, Belgium, Czechia, France, Germany, Ireland, Italy, Japan, Netherlands, Poland, Spain, Ukraine, United Kingdom, United States

Participant flow

Recruitment details

This Phase 2, placebo-controlled study was conducted in subjects diagnosed with amyotrophic lateral sclerosis (ALS). A total of 249 subjects were randomized in a 2:1 ratio to either receive pegcetacoplan or placebo.

Pre-assignment details

Study consisted of 5 periods: 6-week screening period, 52-week randomized treatment period (RTP), 52-week open-label treatment period (OLP), 52-week long-term extension treatment period and a 6-week off-treatment follow-up period. Study was terminated early during OLP due to lack of efficacy as determined by the Week 52 data and no safety concerns.

Participants by arm

Arm	Count
RTP: Pegcetacoplan Subjects received pegcetacoplan 1080 milligram (mg) subcutaneous (SC) infusion twice per week for 52 weeks in the RTP. Eligible subjects entered OLP and continued to receive pegcetacoplan 1080 mg SC infusion twice per week up to 104 weeks. Those subjects experiencing clinical benefit as per investigator continued to receive pegcetacoplan 1080 mg SC infusion twice per week up to 156 weeks in the open-label long-term extension treatment period.	169
RTP: Placebo Subjects received placebo matched to pegcetacoplan SC infusion twice per week for 52 weeks in the RTP. Eligible subjects entered OLP to receive pegcetacoplan 1080 mg SC infusion twice per week up to 104 weeks. Those subjects experiencing clinical benefit as per investigator continued to receive pegcetacoplan 1080 mg SC infusion twice per week up to 156 weeks in the open-label long-term extension treatment period.	80
Total	249

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
OLP (From Week 52 up to Week 104)	Adverse Event	0	0	2	0
OLP (From Week 52 up to Week 104)	Death	0	0	10	6
OLP (From Week 52 up to Week 104)	Physician Decision	0	0	3	1
OLP (From Week 52 up to Week 104)	Sponsor request	0	0	63	31
OLP (From Week 52 up to Week 104)	Withdrawal by Subject	0	0	19	12
RTP (Up to Week 52)	Adverse Event	4	3	0	0
RTP (Up to Week 52)	Death	24	9	0	0
RTP (Up to Week 52)	Lost to Follow-up	1	0	0	0
RTP (Up to Week 52)	Other	2	0	0	0
RTP (Up to Week 52)	Physician Decision	4	1	0	0
RTP (Up to Week 52)	Progressive disease	1	0	0	0
RTP (Up to Week 52)	Site terminated by sponsor	7	5	0	0
RTP (Up to Week 52)	Study terminated by sponsor	2	0	0	0
RTP (Up to Week 52)	Withdrawal by Subject	25	11	0	0

Baseline characteristics

Characteristic	Total	RTP: Placebo	RTP: Pegcetacoplan
Age, Continuous	57.2 years STANDARD_DEVIATION 12.01	57.7 years STANDARD_DEVIATION 11.02	57.0 years STANDARD_DEVIATION 12.47
Ethnicity (NIH/OMB) Hispanic or Latino	42 Participants	15 Participants	27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	186 Participants	62 Participants	124 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	21 Participants	3 Participants	18 Participants
Race/Ethnicity, Customized Black or African American	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Caucasian	197 Participants	67 Participants	130 Participants
Race/Ethnicity, Customized North East Asian	20 Participants	6 Participants	14 Participants
Race/Ethnicity, Customized Other	18 Participants	5 Participants	13 Participants
Race/Ethnicity, Customized South East Asian	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Unknown	14 Participants	2 Participants	12 Participants
Sex: Female, Male Female	89 Participants	25 Participants	64 Participants
Sex: Female, Male Male	160 Participants	55 Participants	105 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	26 / 169	11 / 80	10 / 97	6 / 50
other Total, other adverse events	124 / 169	55 / 80	31 / 97	20 / 50
serious Total, serious adverse events	57 / 169	27 / 80	24 / 97	14 / 50

Outcome results

Primary

OLP: Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events

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.

Time frame: From first dose of study drug (Week 52) up to 56 days post last dose of study drug, approximately 60 weeks

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
RTP: Pegcetacoplan	OLP: Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events	TEAEs	54 Participants
RTP: Pegcetacoplan	OLP: Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events	TESAEs	24 Participants
RTP: Placebo	OLP: Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events	TEAEs	33 Participants
RTP: Placebo	OLP: Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events	TESAEs	14 Participants

Primary

OLP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale up to Week 104

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.

Time frame: From Baseline (Week 52) up to Week 104

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
RTP: Pegcetacoplan	OLP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale up to Week 104	SI only	11 Participants
RTP: Pegcetacoplan	OLP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale up to Week 104	SB only	0 Participants
RTP: Pegcetacoplan	OLP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale up to Week 104	SI and SB	1 Participants
RTP: Placebo	OLP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale up to Week 104	SI only	3 Participants
RTP: Placebo	OLP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale up to Week 104	SB only	0 Participants
RTP: Placebo	OLP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale up to Week 104	SI and SB	0 Participants

Primary

RTP: Combined Assessment of Function and Survival (CAFS) Rank Score (Joint-Rank Score) at Week 52

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.

Time frame: Week 52

Population: 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.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
RTP: Pegcetacoplan	RTP: Combined Assessment of Function and Survival (CAFS) Rank Score (Joint-Rank Score) at Week 52	123.0 score on a scale	Standard Error 4.71
RTP: Placebo	RTP: Combined Assessment of Function and Survival (CAFS) Rank Score (Joint-Rank Score) at Week 52	126.0 score on a scale	Standard Error 6.89

Comparison: Analysis of covariance (ANCOVA) was used to analyze the ranks of the CAFS score with treatment as a fixed effect, adjusted for baseline ALSFRS-R total score, time from symptom onset, baseline Log neurofilament light chain (NfL), and the randomization stratification factors (location of first muscle weakness and use of riluzole and edaravone).p-value: 0.720595% CI: [-19.5, 13.5]ANCOVA

Primary

RTP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) up to Week 52

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.

Time frame: Baseline (Day 1) up to Week 52

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
RTP: Pegcetacoplan	RTP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) up to Week 52	SI only	16 Participants
RTP: Pegcetacoplan	RTP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) up to Week 52	SB only	0 Participants
RTP: Pegcetacoplan	RTP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) up to Week 52	SI and SB	1 Participants
RTP: Placebo	RTP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) up to Week 52	SI only	6 Participants
RTP: Placebo	RTP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) up to Week 52	SB only	0 Participants
RTP: Placebo	RTP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) up to Week 52	SI and SB	0 Participants

Primary

RTP: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Time frame: From first dose of study drug (Day 1) up to 56 days post last dose of study drug, approximately 60 weeks

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
RTP: Pegcetacoplan	RTP: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TEAEs	137 Participants
RTP: Pegcetacoplan	RTP: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TESAEs	57 Participants
RTP: Placebo	RTP: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TEAEs	61 Participants
RTP: Placebo	RTP: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TESAEs	27 Participants

Secondary

Number of Subjects With an Event of Death During the Study

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

Time frame: RTP: Baseline (Day 1) up to Week 52; OLP: Baseline (Week 52) up to Week 104

Population: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
RTP: Pegcetacoplan	Number of Subjects With an Event of Death During the Study	26 Participants
RTP: Placebo	Number of Subjects With an Event of Death During the Study	11 Participants
OLP: Pegcetacoplan/Pegcetacoplan	Number of Subjects With an Event of Death During the Study	10 Participants
OLP: Placebo/Pegcetacoplan	Number of Subjects With an Event of Death During the Study	6 Participants

Secondary

OLP: Change From Baseline in ALS Assessment Questionnaire-40 at Week 104

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.