An Efficacy and Safety Study of Ravulizumab in ALS Partic... | NCT04248465

ID	Type	Description	Link
2019-004619-30	EudraCT Number

Status Module

Oversight Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Ravulizumab	Experimental	Participants will receive ravulizumab for the duration of the study.	Biological: Ravulizumab
Placebo	Placebo Comparator	Participants will receive placebo during the 50-week Randomized Controlled Period of the study, after which they will enter the Open-label Extension Period of the study and switch to receive ravulizumab.	Drug: Placebo Biological: Ravulizumab

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Single loading dose via intravenous infusion, followed by regular maintenance dosing, based on weight.	Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline In Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score	The ALSFRS-Revised is a validated instrument for evaluating the levels of the functional status of participants with amyotrophic lateral sclerosis (ALS) in 4 areas, including bulbar, gross motor activity, fine motor activity, and respiratory functions. The scale included 12 functional items and each item is rated on a 0 to 4 scale, with a maximum total score of 48. A higher score indicated greater retention of function. Baseline was defined as last non-missing value on or before first study drug administration.	Baseline, Week 50

Secondary Outcomes

Measure	Description	Time Frame
Time To Ventilator Assistance-free Survival	Ventilation Assistance-Free Survival (VAFS) is a composite endpoint of survival and severe and irreversible respiratory decline. The use of VAFS allowed for the collection of survival data that was not impacted by survival prolongation from noninvasive or permanent ventilatory interventions which could prolong life without impacting underlying disease progression.

Eligibility Module

Facility	Status	City	State	ZIP	Country	Contacts
Barrow Neurological Institute		Phoenix	Arizona	85013	United States
Neuromuscular Research Center and Clinic

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37695623	Derived	Genge A, van den Berg LH, Frick G, Han S, Abikoff C, Simmons A, Lin Q, Patra K, Kupperman E, Berry JD. Efficacy and Safety of Ravulizumab, a Complement C5 Inhibitor, in Adults With Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Neurol. 2023 Oct 1;80(10):1089-1097. doi: 10.1001/jamaneurol.2023.2851.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Ravulizumab/Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then once every 8 weeks (q8w) up to Week 42 (inclusive) during the Randomized Controlled Period. Then during the Open Label Extension Period, participants received ravulizumab, with a blinded 900 milligrams (mg) dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 23, 2021	Dec 15, 2022

Arm/Group Information

ID	Title	Description
BG000	Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then, during the Open Label Extension Period, participants received ravulizumab, with a blinded 900 mg dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.
BG001	Placebo	Participants received a weight-based loading dose of placebo matched to ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then during the Open Label Extension Period, participants received ravulizumab, with a blinded loading dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00058.6± 10.57 BG00158.0± 11.03 BG00258.4± 10.72

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00094 BG00158 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00022 BG00112 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0012 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline In Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score

The ALSFRS-Revised is a validated instrument for evaluating the levels of the functional status of participants with amyotrophic lateral sclerosis (ALS) in 4 areas, including bulbar, gross motor activity, fine motor activity, and respiratory functions. The scale included 12 functional items and each item is rated on a 0 to 4 scale, with a maximum total score of 48. A higher score indicated greater retention of function. Baseline was defined as last non-missing value on or before first study drug administration.

FAS included all randomized participants who received at least 1 dose of study drug grouped by randomized treatment group. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 50

ID	Title	Description
OG000	Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then, during the Open Label Extension Period, participants received ravulizumab, with a blinded 900 mg dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.
OG001	Placebo	Participants received a weight-based loading dose of placebo matched to ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then during the Open Label Extension Period, participants received ravulizumab, with a blinded loading dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.

Units	Counts
Participants	OG00032 OG00114

Title

Denominators

Categories

Title	Measurements
	OG000-11.9± 7.30 OG001-10.6± 6.05

Secondary

Time To Ventilator Assistance-free Survival

Ventilation Assistance-Free Survival (VAFS) is a composite endpoint of survival and severe and irreversible respiratory decline. The use of VAFS allowed for the collection of survival data that was not impacted by survival prolongation from noninvasive or permanent ventilatory interventions which could prolong life without impacting underlying disease progression.

FAS included all randomized participants who received at least 1 dose of study drug grouped by randomized treatment group.

Posted

Median

Full Range

months

Up to Week 50

ID	Title	Description
OG000	Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then, during the Open Label Extension Period, participants received ravulizumab, with a blinded 900 mg dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.
OG001	Placebo	Participants received a weight-based loading dose of placebo matched to ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then during the Open Label Extension Period, participants received ravulizumab, with a blinded loading dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.

Secondary

Change From Baseline In Percent Predicted Slow Vital Capacity

Slow vital capacity measures slow and gradual expulsion of air from the lungs using a spirometer.

Posted

Mean

Standard Deviation

percentage of predicted volume

Baseline, Week 50

ID	Title	Description
OG000	Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then, during the Open Label Extension Period, participants received ravulizumab, with a blinded 900 mg dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.
OG001	Placebo	Participants received a weight-based loading dose of placebo matched to ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then during the Open Label Extension Period, participants received ravulizumab, with a blinded loading dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.

Secondary

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events, and TEAEs Leading To Study Drug Discontinuation

An adverse event (AE) was defined as any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or procedure, whether or not considered related to the medicinal product or procedure, which occurred during the course of the clinical study. TEAEs were defined as AEs that occurred on or after the date and time of study drug administration, or those that first occurred before dosing but worsened in frequency or severity after study drug administration. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Safety Set included all participants who received at least 1 dose of study drug grouped by treatment actually received (for reporting exposure and safety data).

Posted

Count of Participants

Participants

Baseline up to Week 156

ID	Title	Description
OG000	Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then, during the Open Label Extension Period, participants received ravulizumab, with a blinded 900 mg dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.
OG001

Secondary

Change From Baseline In Muscle Strength As Assessed By Handheld Dynamometry

Handheld dynamometry (HHD) is a procedure for quantitative strength testing. Muscle strength testing was performed on prespecified muscles in the upper and lower extremities bilaterally and the force measurements were recorded. Force of measurement is reported in megascores (lower, upper, total). The total megascore is defined as the average of the non-missing ratios over baseline for all the muscles involved. The megascore at baseline is always 100. The range of a potential megascore can not be determined in advance. A megascore >100 indicates more strength compared to baseline.

Posted

Mean

Standard Deviation

% (as the unit of megascore)

Baseline, Week 50

ID	Title	Description
OG000	Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then, during the Open Label Extension Period, participants received ravulizumab, with a blinded 900 mg dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.
OG001	Placebo

Secondary

Change From Baseline In Serum Neurofilament Light Chain

Posted

Mean

Standard Deviation

picograms/milliliter

Baseline, Week 50

ID	Title	Description
OG000	Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then, during the Open Label Extension Period, participants received ravulizumab, with a blinded 900 mg dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.
OG001	Placebo	Participants received a weight-based loading dose of placebo matched to ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then during the Open Label Extension Period, participants received ravulizumab, with a blinded loading dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.

Secondary

Change From Baseline in Serum Ravulizumab Concentration Over the Study Duration

Pharmacokinetic Analysis Set (PKAS) included all participants who received at least 1 dose of the study drug and had at least 1 postdose pharmacokinetic (PK) sample. This endpoint was planned to be reported for Ravulizumab arm only.

Posted

Geometric Mean

Geometric Coefficient of Variation

micrograms/milliliter

Baseline, Predose at Week 50

ID	Title	Description
OG000	Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then, during the Open Label Extension Period, participants received ravulizumab, with a blinded 900 mg dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Serum Free Complement Component 5 (C5) Concentration Over the Study Duration

Pharmacodynamic analysis set (PDAS) included all participants who received at least 1 dose of the study drug and had at least 1 postdose pharmacodynamics (PD) sample. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure. There were no participants with evaluable C5 data in the Placebo arm at Week 50.

Posted

Mean

Standard Deviation

micrograms/milliliter

Baseline, Predose at Week 50

ID	Title	Description
OG000	Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then, during the Open Label Extension Period, participants received ravulizumab, with a blinded 900 mg dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.
OG001	Placebo	Participants received a weight-based loading dose of placebo matched to ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then during the Open Label Extension Period, participants received ravulizumab, with a blinded loading dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.

Secondary

Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1210

Blood samples were collected to evaluate antibody response through development of ADAs.

PDAS included all participants who received at least 1 dose of the study drug and had at least 1 postdose PD sample. Here, Number of Participants analyzed signifies those participants who were evaluable at Week 50. There were no participants with evaluable C5 data in the Placebo arm at Week 50.

Posted

Count of Participants

Participants

Week 50

ID	Title	Description
OG000	Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then, during the Open Label Extension Period, participants received ravulizumab, with a blinded 900 mg dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.
OG001	Placebo	Participants received a weight-based loading dose of placebo matched to ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then during the Open Label Extension Period, participants received ravulizumab, with a blinded loading dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Randomized Controlled Period: Ravulizumab	Participants received a weight-based loading dose of ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive).	15	255	41	255	196	255
EG001	Randomized Controlled Period: Placebo	Participants received a weight-based loading dose of placebo matched to ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive).	6	127	24	127	106	127
EG002	Open Label Extension Period: Ravulizumab	Participants received ravulizumab, with a blinded 900 mg dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.	0	14	2	14	3	14
EG003	Open Label Extension Period: Placebo	Participants received ravulizumab, with a blinded loading dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.	0	5	0	5	1	5

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0008 events8 affected255 at risk EG0014 events4 affected127 at risk EG0020 events0 affected14 at risk EG0030 events0 affected5 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0003 events3 affected255 at risk EG0012 events2 affected127 at risk EG0020 events0 affected14 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Pneumonitis aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0014 events4 affected127 at risk EG0020 events0 affected14 at risk EG003
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Pneumonia	Infections and infestations	MedDRA v24.1	Non-systematic Assessment	EG0003 events3 affected255 at risk EG0016 events5 affected127 at risk EG0020 events0 affected14 at risk EG003
Pneumonia aspiration	Infections and infestations	MedDRA v24.1	Non-systematic Assessment	EG0002 events2 affected255 at risk EG0012 events2 affected127 at risk EG0020 events0 affected14 at risk EG003
Bronchitis	Infections and infestations	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Pneumonia bacterial	Infections and infestations	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Appendicitis	Infections and infestations	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
COVID-19	Infections and infestations	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0021 events1 affected14 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Gastrostomy failure	Injury, poisoning and procedural complications	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Gastrostomy tube site complication	Injury, poisoning and procedural complications	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Colitis ulcerative	Gastrointestinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0012 events2 affected127 at risk EG0020 events0 affected14 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Pancreatitis relapsing	Gastrointestinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Death	General disorders	MedDRA v24.1	Non-systematic Assessment	EG0002 events2 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Complication associated with device	General disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Pyrexia	General disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Amyotrophic lateral sclerosis	Nervous system disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Headache	Nervous system disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Subarachnoid haemorrhage	Nervous system disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Haemorrhage intracranial	Nervous system disorders	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Syncope	Nervous system disorders	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Completed suicide	Psychiatric disorders	MedDRA v24.1	Non-systematic Assessment	EG0002 events2 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Assisted suicide	Psychiatric disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Euglycaemic diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Malnutrition	Metabolism and nutrition disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Myocardial necrosis marker increased	Investigations	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Weight decreased	Investigations	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
SARS-CoV-2 test positive	Investigations	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Cardio-respiratory arrest	Cardiac disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Feeding tube user	Social circumstances	MedDRA v24.1	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Infusion related hypersensitivity reaction	Immune system disorders	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Euthanasia	Surgical and medical procedures	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected127 at risk EG0020 events0 affected14 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0010 events0 affected127 at risk EG0021 events1 affected14 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fall	Injury, poisoning and procedural complications	MedDRA v24.1	Non-systematic Assessment	EG00081 events54 affected255 at risk EG00165 events36 affected127 at risk EG0021 events1 affected14 at risk EG0031 events1 affected5 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA v24.1	Non-systematic Assessment	EG00013 events11 affected255 at risk EG00113 events8 affected127 at risk EG0020 events0 affected14 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA v24.1	Non-systematic Assessment	EG00029 events26 affected255 at risk EG0015 events5 affected127 at risk EG0020 events0 affected14 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA v24.1	Non-systematic Assessment	EG00028 events23 affected255 at risk EG00110 events10 affected127 at risk EG0020 events0 affected14 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA v24.1	Non-systematic Assessment	EG0006 events4 affected255 at risk EG00110 events9 affected127 at risk EG0020 events0 affected14 at risk EG003
Headache	Nervous system disorders	MedDRA v24.1	Non-systematic Assessment	EG00062 events42 affected255 at risk EG00129 events22 affected127 at risk EG0021 events1 affected14 at risk EG003
Fatigue	General disorders	MedDRA v24.1	Non-systematic Assessment	EG00040 events22 affected255 at risk EG00111 events11 affected127 at risk EG0020 events0 affected14 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA v24.1	Non-systematic Assessment	EG00031 events21 affected255 at risk EG0017 events5 affected127 at risk EG0020 events0 affected14 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA v24.1	Non-systematic Assessment	EG00023 events18 affected255 at risk EG0015 events4 affected127 at risk EG0020 events0 affected14 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA v24.1	Non-systematic Assessment	EG00012 events12 affected255 at risk EG00112 events11 affected127 at risk EG0020 events0 affected14 at risk EG003
Insomnia	Psychiatric disorders	MedDRA v24.1	Non-systematic Assessment	EG00014 events13 affected255 at risk EG0018 events8 affected127 at risk EG0020 events0 affected14 at risk EG003
Hordeolum	Infections and infestations	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0010 events0 affected127 at risk EG0020 events0 affected14 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0010 events0 affected127 at risk EG0021 events1 affected14 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA v24.1	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0010 events0 affected127 at risk EG0021 events1 affected14 at risk EG003

Participants received a weight-based loading dose of placebo matched to ravulizumab on Day 1, followed by a weight-based maintenance dose on Day 15, then q8w up to Week 42 (inclusive) during the Randomized Controlled Period. Then during the Open Label Extension Period, participants received ravulizumab, with a blinded loading dose at Week 50, followed by an open-label ravulizumab maintenance dose at Week 52, then q8w for up to 106 weeks of treatment.

ID	Term
D013118	Spinal Cord Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D019636	Neurodegenerative Diseases
D057177	TDP-43 Proteinopathies
D009468	Neuromuscular Diseases
D057165	Proteostasis Deficiencies
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
D000690	Amyotrophic Lateral Sclerosis
D016472	Motor Neuron Disease