Study to Evaluate the Efficacy and Safety of APL-2 in Pat... | NCT03500549

Label	Type	Description	Intervention Names
Pegcetacoplan	Experimental	1080 mg pegcetacoplan administered subcutaneously twice-weekly or every three days.	Drug: Pegcetacoplan Drug: Soliris
Eculizumab	Active Comparator	Complement (C5) Inhibitor.	Drug: Pegcetacoplan Drug: Soliris

Name	Type	Description	Arm Group Labels	Other Names
Pegcetacoplan	Drug	Complement (C3) Inhibitor	Eculizumab Pegcetacoplan

Measure	Description	Time Frame
Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP	Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.	Baseline and Week 16

Measure	Description	Time Frame
Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP	Subjects who experienced more than 1 transfusion during the RCP are only counted once. Subjects who did not have a transfusion but withdrew before Week 16 were considered as having a transfusion in the analysis of transfusion avoidance.	Day 1 to Week 16

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

At least 18 years of age
Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry
On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3 months prior to the Screening Visit
Hb <10.5 g/dL at the Screening Visit
Absolute reticulocyte count > 1.0x ULN at the Screening Visit
Platelet count of >50,000/mm3 at the Screening Visit
Absolute neutrophil count >500/mm3 at the Screening Visit
Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with APL-2. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
Women of child-bearing potential (WOCBP) must have a negative pregnancy test at the Screening and Day -28 Visit (Run-in Period) and must agree to use protocol defined methods of contraception for the duration of the study and 90 days after their last dose of study drug
Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 90 days after their last dose of study drug
Willing and able to give informed consent
Willing and able to self-administer APL-2 (administration by caregiver will be allowed)
Have a body mass index (BMI) ≤35.0 kg/m2

Exclusion Criteria:

Active bacterial infection that has not resolved within 14 week of Day -28 (first dose of APL-2)
Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4 weeks prior to Screening
Hereditary complement deficiency
History of bone marrow transplantation
History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration
Participation in any other investigational drug trial or exposure to other investigational agent within 30 days or 5 half-lives (whichever is longer)
Currently breast-feeding women
Inability to cooperate or any condition that, in the opinion of the investigator, could increase the subject's risk of participating in the study or confound the outcome of the study

This study includes cardiac safety evaluations. The following cardiac eligibility criteria are necessary to avoid confounding the cardiac safety outcomes:

History or family history of Long QT Syndrome or torsade de pointes, unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden death
Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class >2
QTcF > 470 ms, PR > 280 ms
Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities
Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetron or pentamidine at screening
Receiving any other QTc-prolonging drugs (see Appendix 4 in Section 19.4), at a stable dose for less than 3 weeks prior to dosing
Receiving prophylactic ciprofloxacin, erythromycin or azithromycin for less than one week prior to the first dose of study medication (must have a repeat screening ECG after one week of prophylactic antibiotics with QTcF < 470 ms)

Facility	Status	City	State	ZIP	Country	Contacts
University of Southern California		Los Angeles	California	90033	United States
Sarcoma Oncology Research Center

PubMed Identifier	Type	Citation	Retractions
40720060	Derived	de Castro C, Kelly RJ, Griffin M, Patriquin CJ, Mulherin B, Hochsmann B, Selvaratnam V, Wong RSM, Hillmen P, Horneff R, Uchendu UO, Zhang Y, Surova E, Szamosi J, de Latour RP. Efficacy and Safety Maintained up to 3 Years in Adults with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan. Adv Ther. 2025 Sep;42(9):4641-4658. doi: 10.1007/s12325-025-03310-8. Epub 2025 Jul 28.
40285403

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly subcutaneous (SC) doses of pegcetacoplan 1080 milligrams (mg) in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

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	Aug 16, 2019	Oct 7, 2021

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

Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP

Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.

The ITT set included all randomized subjects.

Posted

Least Squares Mean

Standard Error

Grams per deciliter (g/dL)

Baseline and Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Units	Counts
Participants	OG00041 OG00139

Title

Denominators

Categories

Title	Measurements
	OG0002.37± 0.363 OG001-1.47± 0.666

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		MMRM		<0.0001	Superiority was tested at the 5% level. MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.	LS mean difference	3.84			2-Sided	95	2.33	5.34					Superiority	The primary endpoint analysis was a between-treatment-group comparison using a mixed effect model for repeated measures (MMRM). The difference between pegcetacoplan and eculizumab LS mean Hb changes from Baseline at Week 16 was calculated along with its 2-sided 95% confidence interval (CI) and associated P-value from the MMRM model for the ITT set, censored for transfusions.

Secondary

Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP

Subjects who experienced more than 1 transfusion during the RCP are only counted once. Subjects who did not have a transfusion but withdrew before Week 16 were considered as having a transfusion in the analysis of transfusion avoidance.

The ITT set included all randomized subjects.

Posted

Number

Percentage of subjects

Day 1 to Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP

Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.

The ITT set included all randomized subjects.

Posted

Least Squares Mean

Standard Error

10^9 cells/ liter (L)

Baseline and Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP

The ITT set included all randomized subjects.

Posted

Least Squares Mean

Standard Error

Units (U)/L

Baseline and Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP

The FACIT-fatigue scale version 4 is a 13-item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. A higher score corresponds to a higher quality of life (QoL). Baseline was the last available, nonmissing observation before taking the first dose of pegcetacoplan. Data collected after transfusion is excluded from analysis.

The ITT set included all randomized subjects.

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline and Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16

Hb response was defined as an increase of at least 1 g/dL in Hb from Baseline at Week 16. Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.

The ITT set included all randomized subjects.

Posted

Number

Percentage of subjects

Baseline and Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16

Reticulocyte normalization was defined as the ARC being below the upper limit of the gender-specific normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 were classified as nonresponders.

The ITT set includes all randomized subjects.

Posted

Number

Percentage of subjects

Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16

Hb normalization was defined as the Hb level being above the lower limit of the normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 are classified as nonnormalization.

The ITT set included all randomized subjects.

Posted

Number

Percentage of subjects

Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP

The ITT set included all randomized subjects.

Posted

Least Squares Mean

Standard Error

Micromole (μmol)/L

Baseline and Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP

The ITT set included all randomized subjects.

Posted

Least Squares Mean

Standard Error

g/L

Baseline and Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP

The LASA consists of 3 items, where the respondents were asked to rate their perceived level of functioning. Specific domains included activity level, ability to carry out daily activities, and an item for overall QoL. Their level of functioning was reported on a 0 to 100 scale with 0 indicates "As low as could be" and 100 indicates "As high as could be". The combined score ranged from 0 to 300, with higher scores corresponding to a higher QoL.

The ITT set included all randomized subjects.

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline and Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

LS Mean Change From Baseline to Week 16 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Scale (QLQ-C30) Scores During the RCP

The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are designated by functional scales, symptom scales, and global subject QoL/overall perceived health status. For the first 28 questions the 4 possible responses are "Not at all' (1), 'A little' (2), 'Quite a bit' (3) and 'Very much' (4). For the remaining 2 questions the response is requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.

The ITT set included all randomized subjects.

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline and Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001

Secondary

Total Number of PRBC Units Transfused During the RCP

Subjects who withdrew during the RCP before Week 16 will have their number of units of PRBC estimated from the duration they were in the study.

The ITT set included all randomized subjects.

Posted

Number

PRBC units

Day 1 to Week 16

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

g/dL

Baseline and Week 48

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

g/dL

Week 17 and Week 48

ID	Title	Description
OG000	Open-label Period: Continue Pegcetacoplan	On Day 1 of the RCP, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Open-label Period: Crossover to Pegcetacoplan	Subjects entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before receiving monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Units	Counts
Participants

Secondary

Mean Change From Baseline to Week 48 in ARC During the Treatment Period

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

10^9 cells/L

Baseline and Week 48

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Mean Change From Week 17 to Week 48 in ARC During the Open-label Period

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

10^9 cells/L

Week 17 and Week 48

ID	Title	Description
OG000	Open-label Period: Continue Pegcetacoplan	On Day 1 of the RCP, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Open-label Period: Crossover to Pegcetacoplan	Subjects entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before receiving monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Units	Counts
Participants

Secondary

Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

U/L

Baseline and Week 48

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

U/L

Week 17 and Week 48

ID	Title	Description
OG000	Open-label Period: Continue Pegcetacoplan	On Day 1 of the RCP, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Open-label Period: Crossover to Pegcetacoplan	Subjects entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before receiving monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Units	Counts
Participants

Secondary

Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period

The FACIT-fatigue scale version 4 is a 13-item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. A higher score corresponds to a higher QoL. Baseline was the last available, nonmissing observation before taking the first dose of pegcetacoplan. Data collected after transfusion is excluded from analysis.

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

Score on a scale

Baseline and Week 48

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period

The FACIT-fatigue scale is a 13 item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. Higher score corresponds to a higher QoL.

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

Score on a scale

Week 17 and Week 48

ID	Title	Description
OG000	Open-label Period: Continue Pegcetacoplan	On Day 1 of the RCP, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Open-label Period: Crossover to Pegcetacoplan	Subjects entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before receiving monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

Score on a scale

Baseline and Week 48

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

Score on a scale

Week 17 and Week 48

ID	Title	Description
OG000	Open-label Period: Continue Pegcetacoplan	On Day 1 of the RCP, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Open-label Period: Crossover to Pegcetacoplan	Subjects entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before receiving monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period

The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are designated by functional scales, symptom scales, and global subject QoL/overall perceived health status. For the first 28 questions the 4 possible responses are 'Not at all' (1), 'A little' (2), 'Quite a bit' (3) and 'Very much' (4). For the remaining 2 questions the response is requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

Score on a scale

Baseline and Week 48

ID	Title	Description
OG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Eculizumab to Pegcetacoplan

Secondary

Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period

The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are designated by functional scales, symptom scales, and global subject QoL/overall perceived health status. For the first 28 questions the 4 possible responses are 'Not at all' (1), 'A little' (2), 'Quite a bit' (3) and 'Very much' (4). For the remaining 2 questions the response is requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.

The ITT set included all randomized subjects.

Posted

Mean

Standard Deviation

Score on a scale

Week 17 and Week 48

ID	Title	Description
OG000	Open-label Period: Continue Pegcetacoplan	On Day 1 of the RCP, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Open-label Period: Crossover to Pegcetacoplan	Subjects entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before receiving monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).

Secondary

Total Number of PRBC Units Transfused During the Open-Label Period

Number of units of PRBC transfused to subjects in the open-label period are reported.

The ITT set included all randomized subjects.

Posted

Number

PRBC Units

Week 17 to Week 48

ID	Title	Description
OG000	Open-label Period: Continue Pegcetacoplan	On Day 1 of the RCP, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG001	Open-label Period: Crossover to Pegcetacoplan	Subjects entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before receiving monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
OG002	Open-label Run-in Period: Crossover to Pegcetacoplan	Subjects in the open-label run-in period received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20).

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	Run-in Period: Pegcetacoplan + Eculizumab	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. During the 4-week open-label run-in period (Week 17 to Week 20) subjects randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks during the RCP also received twice-weekly SC doses of pegcetacoplan 1080 mg.	0	80	4	80	71	80
EG001	Open-label Period: Pegcetacoplan	The subjects who were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days during the RCP continued to receive monotherapy with pegcetacoplan until the end of the open-label period (Week 17 to Week 48). Subjects randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks during the RCP received monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days after the open-label run-in period, up to the end of the open-label period (Week 20 to Week 48).	1	77	18	77	71	77
EG002	RCP: Eculizumab	Subjects randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks during the RCP.	0	39	5	39	36	39
EG003	RCP: Pegcetacoplan	Subjects randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days during the RCP.	0	41	7	41	36	41

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Deep vein thrombosis	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG0030 events0 affected41 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Diffuse large B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Allergy to immunoglobulin therapy	Immune system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Pyrexia	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0010 events0 affected77 at risk EG0020 events0 affected39 at risk EG003
Hyperthermia	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0010 events0 affected77 at risk EG0021 events1 affected39 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0010 events0 affected77 at risk EG0020 events0 affected39 at risk EG003
Haemolysis	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected80 at risk EG0015 events5 affected77 at risk EG0021 events1 affected39 at risk EG003
Cytopenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Haemolytic anaemia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0021 events1 affected39 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0010 events0 affected77 at risk EG0022 events2 affected39 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0010 events0 affected77 at risk EG0020 events0 affected39 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Hypersensitivity pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Facial paralysis	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0010 events0 affected77 at risk EG0020 events0 affected39 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0021 events1 affected39 at risk EG003
Intestinal ischaemia	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Oedematous pancreatitis	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Hepatocellular injury	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0010 events0 affected77 at risk EG0021 events1 affected39 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0010 events0 affected77 at risk EG0021 events1 affected39 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0010 events0 affected77 at risk EG0021 events1 affected39 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Haematoma muscle	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
COVID-19	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected77 at risk EG0020 events0 affected39 at risk EG003
Bacterial infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0010 events0 affected77 at risk EG0020 events0 affected39 at risk EG003
Biliary sepsis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Diverticulitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Post procedural sepsis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Sepsis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected77 at risk EG0020 events0 affected39 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertension	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0014 events3 affected77 at risk EG0021 events1 affected39 at risk EG0033 events3 affected41 at risk
Injection site erythema	General disorders	MedDRA (20.0)	Systematic Assessment	EG00075 events33 affected80 at risk EG001127 events9 affected77 at risk EG0020 events0 affected39 at risk EG003
Fatigue	General disorders	MedDRA (20.0)	Systematic Assessment	EG0005 events5 affected80 at risk EG00111 events8 affected77 at risk EG0027 events6 affected39 at risk EG003
Pyrexia	General disorders	MedDRA (20.0)	Systematic Assessment	EG0006 events6 affected80 at risk EG0019 events6 affected77 at risk EG0021 events1 affected39 at risk EG003
Injection site pruritus	General disorders	MedDRA (20.0)	Systematic Assessment	EG00014 events12 affected80 at risk EG0017 events5 affected77 at risk EG0020 events0 affected39 at risk EG003
Asthenia	General disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected80 at risk EG0014 events4 affected77 at risk EG0027 events5 affected39 at risk EG003
Injection site bruising	General disorders	MedDRA (20.0)	Systematic Assessment	EG0003 events2 affected80 at risk EG0017 events3 affected77 at risk EG0020 events0 affected39 at risk EG003
Injection site induration	General disorders	MedDRA (20.0)	Systematic Assessment	EG00012 events5 affected80 at risk EG00127 events5 affected77 at risk EG0020 events0 affected39 at risk EG003
Injection site reaction	General disorders	MedDRA (20.0)	Systematic Assessment	EG00026 events8 affected80 at risk EG0018 events2 affected77 at risk EG0020 events0 affected39 at risk EG003
Injection site swelling	General disorders	MedDRA (20.0)	Systematic Assessment	EG00018 events10 affected80 at risk EG0014 events1 affected77 at risk EG0020 events0 affected39 at risk EG003
Injection site pain	General disorders	MedDRA (20.0)	Systematic Assessment	EG00013 events6 affected80 at risk EG00168 events4 affected77 at risk EG0020 events0 affected39 at risk EG003
Vaccination site pain	General disorders	MedDRA (20.0)	Systematic Assessment	EG0003 events3 affected80 at risk EG0010 events0 affected77 at risk EG0022 events2 affected39 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected80 at risk EG0015 events4 affected77 at risk EG0022 events2 affected39 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0022 events2 affected39 at risk EG003
Vaccination complication	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0003 events2 affected80 at risk EG0012 events2 affected77 at risk EG0020 events0 affected39 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0003 events3 affected80 at risk EG0014 events4 affected77 at risk EG0020 events0 affected39 at risk EG003
Palpitations	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events1 affected80 at risk EG0011 events1 affected77 at risk EG0022 events2 affected39 at risk EG003
Haemolysis	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected80 at risk EG00114 events13 affected77 at risk EG00214 events9 affected39 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected80 at risk EG0015 events3 affected77 at risk EG0020 events0 affected39 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events2 affected77 at risk EG0025 events5 affected39 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected80 at risk EG0019 events9 affected77 at risk EG0021 events1 affected39 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0017 events6 affected77 at risk EG0023 events3 affected39 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0004 events4 affected80 at risk EG0012 events2 affected77 at risk EG0024 events3 affected39 at risk EG003
Headache	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG00012 events10 affected80 at risk EG00113 events8 affected77 at risk EG00210 events9 affected39 at risk EG003
Dizziness	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0003 events3 affected80 at risk EG0013 events3 affected77 at risk EG0025 events5 affected39 at risk EG003
Lethargy	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0010 events0 affected77 at risk EG0022 events2 affected39 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG00011 events10 affected80 at risk EG00115 events11 affected77 at risk EG0022 events2 affected39 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected80 at risk EG0013 events3 affected77 at risk EG0023 events3 affected39 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected80 at risk EG0014 events4 affected77 at risk EG0021 events1 affected39 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0008 events7 affected80 at risk EG0014 events2 affected77 at risk EG0022 events2 affected39 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected80 at risk EG0013 events3 affected77 at risk EG0024 events4 affected39 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected77 at risk EG0022 events2 affected39 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events2 affected77 at risk EG0023 events3 affected39 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0014 events4 affected77 at risk EG0020 events0 affected39 at risk EG003
Chromaturia	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0003 events3 affected80 at risk EG0012 events2 affected77 at risk EG0023 events2 affected39 at risk EG003
Haemoglobinuria	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected77 at risk EG0022 events2 affected39 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0013 events3 affected77 at risk EG0022 events2 affected39 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0013 events3 affected77 at risk EG0020 events0 affected39 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected80 at risk EG0017 events6 affected77 at risk EG0022 events2 affected39 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0003 events3 affected80 at risk EG0016 events5 affected77 at risk EG0022 events2 affected39 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0003 events3 affected80 at risk EG0012 events2 affected77 at risk EG0024 events4 affected39 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0003 events3 affected80 at risk EG0014 events4 affected77 at risk EG0023 events1 affected39 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected77 at risk EG0022 events2 affected39 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0005 events4 affected80 at risk EG00113 events12 affected77 at risk EG0022 events2 affected39 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected80 at risk EG0018 events7 affected77 at risk EG0021 events1 affected39 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected80 at risk EG0017 events7 affected77 at risk EG0022 events2 affected39 at risk EG003
Oral herpes	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected80 at risk EG0017 events6 affected77 at risk EG0020 events0 affected39 at risk EG003
Sinusitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected80 at risk EG0013 events3 affected77 at risk EG0022 events2 affected39 at risk EG003

ID	Term
D000743	Anemia, Hemolytic
D000740	Anemia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D009190	Myelodysplastic Syndromes
D001855	Bone Marrow Diseases

ID	Title	Description
BG000	Pegcetacoplan to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
BG001	Eculizumab to Pegcetacoplan	During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48).
BG002	Total	Total of all reporting groups