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Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

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ClinicalTrials.gov Identifier: NCT03500549
Recruitment Status : Completed
First Posted : April 18, 2018
Results First Posted : March 25, 2022
Last Update Posted : March 25, 2022
Sponsor:
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Paroxysmal Nocturnal Hemoglobinuria
Interventions Drug: Pegcetacoplan
Drug: Soliris
Enrollment 80
Recruitment Details This Phase 3, randomized, multicenter, open-label, active-comparator controlled study evaluated the efficacy and safety of pegcetacoplan (APL-2) in subjects with paroxysmal nocturnal hemoglobinuria who had received treatment with eculizumab (Soliris®) in the past.
Pre-assignment Details The treatment period of the study consisted of 3 parts: a 4-week run-in period, a 16-week randomized controlled period (RCP), and a 32-week open-label period. Of the 102 subjects screened, 80 subjects met all the inclusion criteria and none of the exclusion criteria and entered the run-in period. Randomization was stratified by the number of packed red blood cell (PRBC) transfusions within the 12 months prior to Day -28 and platelet count at screening.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description 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). 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).
Period Title: Run-in Period (Day -28 to ≤Day 1)
Started 41 39
Completed 41 39
Not Completed 0 0
Period Title: RCP (Day 1 - Week 16)
Started 41 39
Completed [1] 38 39
Not Completed 3 0
Reason Not Completed
Adverse Event             3             0
[1]
Completed treatment at Week 16 analysis.
Period Title: Open-label Period (Week 17 to Week 48)
Started 38 39
Completed [1] 35 32
Not Completed 3 7
Reason Not Completed
Adverse Event             3             7
[1]
Completed treatment at Week 48 analysis.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan Total
Hide Arm/Group Description 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). 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). Total of all reporting groups
Overall Number of Baseline Participants 41 39 80
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) set included all randomized subjects.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 80 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
31
  75.6%
32
  82.1%
63
  78.8%
>=65 years
10
  24.4%
7
  17.9%
17
  21.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 80 participants
Female
27
  65.9%
22
  56.4%
49
  61.3%
Male
14
  34.1%
17
  43.6%
31
  38.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 80 participants
Hispanic or Latino
2
   4.9%
1
   2.6%
3
   3.8%
Not Hispanic or Latino
29
  70.7%
32
  82.1%
61
  76.3%
Unknown or Not Reported
10
  24.4%
6
  15.4%
16
  20.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 80 participants
Asian
5
  12.2%
7
  17.9%
12
  15.0%
Black or African American
2
   4.9%
0
   0.0%
2
   2.5%
White
24
  58.5%
25
  64.1%
49
  61.3%
Other
0
   0.0%
1
   2.6%
1
   1.3%
Not Reported
10
  24.4%
6
  15.4%
16
  20.0%
Number of transfusions in the last 12 months prior to Day -28  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 80 participants
< 4
20
  48.8%
16
  41.0%
36
  45.0%
≥ 4
21
  51.2%
23
  59.0%
44
  55.0%
Platelet count at screening  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 80 participants
<100,000 (count/mm^3)
12
  29.3%
9
  23.1%
21
  26.3%
≥100,000 (count/mm^3)
29
  70.7%
30
  76.9%
59
  73.8%
1.Primary Outcome
Title Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP
Hide Description 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Least Squares Mean (Standard Error)
Unit of Measure: Grams per deciliter (g/dL)
2.37  (0.363) -1.47  (0.666)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.0001
Comments 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.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 3.84
Confidence Interval (2-Sided) 95%
2.33 to 5.34
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP
Hide Description 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.
Time Frame Day 1 to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Measure Type: Number
Unit of Measure: Percentage of subjects
85.4 15.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Analysis was based on prespecified non-inferiority margins (NIM) and non-inferiority was achieved if the lower confidence limit or upper confidence limit of the 95% CI of the treatment difference met the prespecified NIM of -20%. Stratified Cochran-Mantel Haenszel (CMH) chi-square test was used for treatment comparison and the 95% CI for difference in percentage between treatments is constructed using the stratified (Miettinen-Nurminen) method.
Statistical Test of Hypothesis P-Value <0.0001
Comments Non-inferiority was tested at the 2.5% level.
Method Miettinen-Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.6253
Confidence Interval (2-Sided) 95%
0.4830 to 0.7677
Estimation Comments [Not Specified]
3.Secondary Outcome
Title LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP
Hide Description 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Least Squares Mean (Standard Error)
Unit of Measure: 10^9 cells/ liter (L)
-135.82  (6.543) 27.79  (11.859)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Analysis was based on prespecified NIM and non-inferiority was achieved if the lower confidence limit or upper confidence limit of the 95% CI of the treatment difference met the prespecified NIM of 10.
Statistical Test of Hypothesis P-Value <0.0001
Comments Non-inferiority was tested at the 2.5% level. MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -163.61
Confidence Interval (2-Sided) 95%
-189.91 to -137.30
Estimation Comments [Not Specified]
4.Secondary Outcome
Title LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP
Hide Description 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Least Squares Mean (Standard Error)
Unit of Measure: Units (U)/L
-14.76  (42.708) -10.12  (71.025)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Analysis was based on prespecified NIM and non-inferiority was achieved if the lower confidence limit or upper confidence limit of the 95% CI of the treatment difference met the prespecified NIM of 20.
Statistical Test of Hypothesis P-Value 0.9557
Comments Non-inferiority was tested at the 2.5% level. MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -4.63
Confidence Interval (2-Sided) 95%
-181.30 to 172.04
Estimation Comments [Not Specified]
5.Secondary Outcome
Title LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP
Hide Description 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
9.22  (1.607) -2.65  (2.821)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Other
Comments Non-inferiority was not assessed because of the prespecified hierarchical testing. Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.0005
Comments MRMM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 11.87
Confidence Interval (2-Sided) 95%
5.49 to 18.25
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16
Hide Description 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Measure Type: Number
Unit of Measure: Percentage of subjects
75.6 0.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Other
Comments Stratified CMH chi-square test was used for treatment comparison and the 95% CI for difference in percentage between treatments is constructed using the stratified Miettinen-Nurminen method.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.6745
Confidence Interval (2-Sided) 95%
0.5452 to 0.8039
Estimation Comments The difference in percentage and 95% CI is calculated based on stratified Miettinen-Nurminen method stratified by randomization factor so it it is not a direct difference of two reporting groups.
7.Secondary Outcome
Title Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16
Hide Description 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.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set includes all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Measure Type: Number
Unit of Measure: Percentage of subjects
78.0 2.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Other
Comments Stratified CMH chi-square test was used for treatment comparison and the 95% CI for difference in percentage between treatments is constructed using the stratified Miettinen-Nurminen method.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.6639
Confidence Interval (2-Sided) 95%
0.5309 to 0.7968
Estimation Comments The difference in percentage and 95% CI is calculated based on stratified Miettinen-Nurminen method stratified by randomization factor so it it is not a direct difference of two reporting groups.
8.Secondary Outcome
Title Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16
Hide Description 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.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Measure Type: Number
Unit of Measure: Percentage of subjects
34.1 0.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Other
Comments Stratified CMH chi-square test was used for treatment comparison and the 95% CI for difference in percentage between treatments is constructed using the stratified Miettinen-Nurminen method.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.3043
Confidence Interval (2-Sided) 95%
0.1493 to 0.4593
Estimation Comments The difference in percentage and 95% CI is calculated based on stratified Miettinen-Nurminen method stratified by randomization factor so it it is not a direct difference of two reporting groups.
9.Secondary Outcome
Title LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP
Hide Description 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Least Squares Mean (Standard Error)
Unit of Measure: Micromole (μmol)/L
-17.78  (2.727) 4.15  (4.477)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.0002
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -21.93
Confidence Interval (2-Sided) 95%
-32.49 to -11.36
Estimation Comments [Not Specified]
10.Secondary Outcome
Title LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP
Hide Description 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Least Squares Mean (Standard Error)
Unit of Measure: g/L
-0.02  (0.033) 0.12  (0.063)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.0369
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.28 to -0.01
Estimation Comments [Not Specified]
11.Secondary Outcome
Title LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP
Hide Description 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
49.38  (10.189) -9.72  (18.988)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.0069
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 59.10
Confidence Interval (2-Sided) 95%
16.88 to 101.32
Estimation Comments [Not Specified]
12.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Global Health Status/QoL 15.91  (3.635) -2.71  (8.515)
Functional Scales - Physical functioning 16.92  (2.081) 4.06  (3.605)
Functional Scales - Role functioning 15.39  (3.930) -9.04  (6.954)
Functional Scales - Emotional functioning 7.98  (3.366) 3.86  (7.237)
Functional Scales - Cognitive functioning 5.76  (3.258) -3.80  (6.420)
Functional Scales - Social functioning 15.08  (2.946) 3.82  (6.349)
Symptom Scales - Fatigue -22.93  (3.321) -2.18  (6.644)
Symptom Scales - Nausea and vomiting -0.34  (1.632) -0.33  (3.876)
Symptom Scales - Pain -0.74  (4.323) 2.01  (7.841)
Symptom Scales - Dyspnoea -20.12  (3.488) -5.55  (7.019)
Symptom Scales - Insomnia -9.18  (3.955) -9.50  (7.090)
Symptom Scales - Appetite loss -3.76  (3.357) 4.19  (7.009)
Symptom Scales - Constipation 2.98  (3.248) 1.19  (8.129)
Symptom Scales - Diarrhoea 0.31  (3.711) 1.68  (8.204)
Symptom Scales - Financial difficulties -6.82  (3.853) 0.58  (6.297)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Global Health Status/QoL: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.0486
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 18.62
Confidence Interval (2-Sided) 95%
0.12 to 37.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Functional Scales - Physical functioning: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.0023
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 12.86
Confidence Interval (2-Sided) 95%
4.86 to 20.86
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Functional Scales - Role functioning: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.0027
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 24.43
Confidence Interval (2-Sided) 95%
8.84 to 40.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Functional Scales - Emotional functioning: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.6013
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.11
Confidence Interval (2-Sided) 95%
-11.58 to 19.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Functional Scales - Cognitive functioning: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.1792
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 9.56
Confidence Interval (2-Sided) 95%
-4.52 to 23.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Functional Scales - Social functioning: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.1039
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 11.27
Confidence Interval (2-Sided) 95%
-2.38 to 24.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Symptom Scales - Fatigue: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.0062
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -20.74
Confidence Interval (2-Sided) 95%
-35.29 to -6.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Symptom Scales - Nausea and vomiting: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.9975
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-8.38 to 8.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Symptom Scales - Pain: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.7554
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -2.76
Confidence Interval (2-Sided) 95%
-20.36 to 14.85
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Symptom Scales - Dyspnoea: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.0620
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -14.57
Confidence Interval (2-Sided) 95%
-29.90 to 0.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Symptom Scales - Insomnia: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.9686
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
-15.67 to 16.30
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Symptom Scales - Appetite loss: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.3002
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -7.95
Confidence Interval (2-Sided) 95%
-23.23 to 7.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Symptom Scales - Constipation: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.8374
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.79
Confidence Interval (2-Sided) 95%
-15.70 to 19.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Symptom Scales - Diarrhoea: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.8775
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.38
Confidence Interval (2-Sided) 95%
-19.28 to 16.52
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments Symptom Scales - Financial difficulties: Difference in LS mean
Type of Statistical Test Other
Comments Analysis was a between-treatment-group comparison using an MMRM. The difference between pegcetacoplan and eculizumab LS mean changes from Baseline at Week 16 was calculated along with its 2-sided 95% CI and associated P-value from the MMRM model for the ITT set, censored for transfusions.
Statistical Test of Hypothesis P-Value 0.3066
Comments MMRM includes treatment + baseline value + analysis visit + strata + analysis visit × treatment, where strata is the combination of randomization stratification factors.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -7.40
Confidence Interval (2-Sided) 95%
-21.76 to 6.95
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Total Number of PRBC Units Transfused During the RCP
Hide Description 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.
Time Frame Day 1 to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 41 39
Measure Type: Number
Unit of Measure: PRBC units
26 198
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pegcetacoplan to Pegcetacoplan, Eculizumab to Pegcetacoplan
Comments [Not Specified]
Type of Statistical Test Other
Comments Wilcoxon rank-sum test P-value for the comparison between treatments is based on median using stratified non-parametric analysis. The 95% CI is constructed using Hodges-Lehmann Estimation of Location Shift.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon rank-sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
2.0 to 4.0
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period
Hide Description 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.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 33 30
Mean (Standard Deviation)
Unit of Measure: g/dL
2.47  (1.72) 2.93  (2.09)
15.Secondary Outcome
Title Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period
Hide Description 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.
Time Frame Week 17 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Open-label Period: Continue Pegcetacoplan Open-label Period: Crossover to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 33 29
Mean (Standard Deviation)
Unit of Measure: g/dL
-0.16  (1.154) 2.89  (2.078)
16.Secondary Outcome
Title Mean Change From Baseline to Week 48 in ARC During the Treatment Period
Hide Description 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.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 31 29
Mean (Standard Deviation)
Unit of Measure: 10^9 cells/L
-135.64  (67.90) -128.22  (59.60)
17.Secondary Outcome
Title Mean Change From Week 17 to Week 48 in ARC During the Open-label Period
Hide Description 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.
Time Frame Week 17 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Open-label Period: Continue Pegcetacoplan Open-label Period: Crossover to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 31 29
Mean (Standard Deviation)
Unit of Measure: 10^9 cells/L
-6.50  (26.471) -121.15  (70.969)
18.Secondary Outcome
Title Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period
Hide Description 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.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 33 30
Mean (Standard Deviation)
Unit of Measure: U/L
-41.53  (153.68) -105.27  (315.59)
19.Secondary Outcome
Title Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period
Hide Description 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.
Time Frame Week 17 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Open-label Period: Continue Pegcetacoplan Open-label Period: Crossover to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 33 28
Mean (Standard Deviation)
Unit of Measure: U/L
8.03  (129.285) -46.84  (292.607)
20.Secondary Outcome
Title Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period
Hide Description 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.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 30 29
Mean (Standard Deviation)
Unit of Measure: Score on a scale
10.14  (9.06) 9.62  (10.34)
21.Secondary Outcome
Title Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period
Hide Description 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.
Time Frame Week 17 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Open-label Period: Continue Pegcetacoplan Open-label Period: Crossover to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 30 26
Mean (Standard Deviation)
Unit of Measure: Score on a scale
1.28  (7.805) 10.19  (10.973)
22.Secondary Outcome
Title Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period
Hide Description 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.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 29 29
Mean (Standard Deviation)
Unit of Measure: Score on a scale
58.66  (51.16) 56.52  (65.55)
23.Secondary Outcome
Title Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period
Hide Description 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.
Time Frame Week 17 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Open-label Period: Continue Pegcetacoplan Open-label Period: Crossover to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 30 26
Mean (Standard Deviation)
Unit of Measure: Score on a scale
13.13  (46.296) 62.92  (60.053)
24.Secondary Outcome
Title Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period
Hide Description 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.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Pegcetacoplan to Pegcetacoplan Eculizumab to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 30 28
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Global Health Status/QoL 18.89  (17.635) 13.99  (22.912)
Functional Scales - Physical functioning 15.33  (15.278) 10.80  (17.765)
Functional Scales - Role functioning 16.67  (27.334) 20.11  (27.595)
Functional Scales - Emotional functioning 10.28  (18.657) 5.36  (17.005)
Functional Scales - Cognitive functioning 7.78  (23.462) 0.00  (18.703)
Functional Scales - Social functioning 16.11  (24.166) 14.88  (22.379)
Symptom Scales - Fatigue -21.48  (26.733) -23.75  (29.506)
Symptom Scales - Nausea and vomiting -2.22  (11.357) 0.00  (4.454)
Symptom Scales - Pain 0.56  (27.849) 3.45  (20.596)
Symptom Scales - Dyspnoea -17.78  (29.985) -27.59  (33.415)
Symptom Scales - Insomnia -6.67  (25.371) 0.00  (28.172)
Symptom Scales - Appetite loss -7.78  (14.339) -3.45  (22.440)
Symptom Scales - Constipation -1.11  (22.289) -2.38  (8.742)
Symptom Scales - Diarrhoea 1.11  (29.664) 5.95  (15.853)
Symptom Scales - Financial difficulties -15.56  (24.343) -8.33  (19.510)
25.Secondary Outcome
Title Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period
Hide Description 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.
Time Frame Week 17 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Open-label Period: Continue Pegcetacoplan Open-label Period: Crossover to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 30 26
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Global Health Status/QoL 7.22  (19.664) 23.08  (22.149)
Functional Scales - Physical functioning 0.89  (10.168) 11.03  (17.173)
Functional Scales - Role functioning 5.00  (20.599) 19.87  (22.617)
Functional Scales - Emotional functioning -2.22  (27.328) 1.92  (13.806)
Functional Scales - Cognitive functioning -2.78  (16.999) 2.56  (24.355)
Functional Scales - Social functioning 3.89  (18.919) 12.18  (23.361)
Symptom Scales - Fatigue -2.96  (20.824) -23.08  (28.790)
Symptom Scales - Nausea and vomiting -2.22  (5.762) -4.49  (12.072)
Symptom Scales - Pain -2.78  (23.195) -5.77  (21.051)
Symptom Scales - Dyspnoea 3.33  (25.295) -19.23  (28.555)
Symptom Scales - Insomnia 8.89  (23.050) -5.13  (27.797)
Symptom Scales - Appetite loss -8.89  (26.164) -5.13  (22.494)
Symptom Scales - Constipation -1.11  (20.498) -1.28  (11.473)
Symptom Scales - Diarrhoea -4.44  (28.679) 3.85  (27.206)
Symptom Scales - Financial difficulties -2.22  (12.172) -2.56  (16.119)
26.Secondary Outcome
Title Total Number of PRBC Units Transfused During the Open-Label Period
Hide Description Number of units of PRBC transfused to subjects in the open-label period are reported.
Time Frame Week 17 to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included all randomized subjects.
Arm/Group Title Open-label Period: Continue Pegcetacoplan Open-label Period: Crossover to Pegcetacoplan Open-label Run-in Period: Crossover to Pegcetacoplan
Hide Arm/Group Description:
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).
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).
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).
Overall Number of Participants Analyzed 38 39 38
Measure Type: Number
Unit of Measure: PRBC Units
68 110 14
Time Frame Day -28 to Week 54, a maximum of approximately 58 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Run-in Period: Pegcetacoplan + Eculizumab Open-label Period: Pegcetacoplan RCP: Eculizumab RCP: Pegcetacoplan
Hide Arm/Group Description 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. 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). Subjects randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks during the RCP. Subjects randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days during the RCP.
All-Cause Mortality
Run-in Period: Pegcetacoplan + Eculizumab Open-label Period: Pegcetacoplan RCP: Eculizumab RCP: Pegcetacoplan
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/80 (0.00%)      1/77 (1.30%)      0/39 (0.00%)      0/41 (0.00%)    
Hide Serious Adverse Events
Run-in Period: Pegcetacoplan + Eculizumab Open-label Period: Pegcetacoplan RCP: Eculizumab RCP: Pegcetacoplan
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/80 (5.00%)      18/77 (23.38%)      5/39 (12.82%)      7/41 (17.07%)    
Blood and lymphatic system disorders         
Haemolysis † 1  1/80 (1.25%)  1 5/77 (6.49%)  5 1/39 (2.56%)  1 2/41 (4.88%)  2
Cytopenia † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Haemolytic anaemia † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 1/39 (2.56%)  1 0/41 (0.00%)  0
Thrombocytopenia † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Anaemia † 1  0/80 (0.00%)  0 0/77 (0.00%)  0 2/39 (5.13%)  2 0/41 (0.00%)  0
Cardiac disorders         
Atrial fibrillation † 1  0/80 (0.00%)  0 0/77 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0
Gastrointestinal disorders         
Abdominal pain † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 1/39 (2.56%)  1 0/41 (0.00%)  0
Intestinal ischaemia † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Oedematous pancreatitis † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Small intestinal obstruction † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
General disorders         
Pyrexia † 1  0/80 (0.00%)  0 0/77 (0.00%)  0 0/39 (0.00%)  0 1/41 (2.44%)  1
Hyperthermia † 1  0/80 (0.00%)  0 0/77 (0.00%)  0 1/39 (2.56%)  1 0/41 (0.00%)  0
Hepatobiliary disorders         
Cholelithiasis † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Hepatocellular injury † 1  0/80 (0.00%)  0 0/77 (0.00%)  0 1/39 (2.56%)  1 0/41 (0.00%)  0
Hyperbilirubinaemia † 1  0/80 (0.00%)  0 0/77 (0.00%)  0 1/39 (2.56%)  1 0/41 (0.00%)  0
Jaundice † 1  0/80 (0.00%)  0 0/77 (0.00%)  0 1/39 (2.56%)  1 0/41 (0.00%)  0
Immune system disorders         
Allergy to immunoglobulin therapy † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Infections and infestations         
COVID-19 † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Gastroenteritis † 1  0/80 (0.00%)  0 2/77 (2.60%)  2 0/39 (0.00%)  0 1/41 (2.44%)  1
Bacterial infection † 1  0/80 (0.00%)  0 0/77 (0.00%)  0 0/39 (0.00%)  0 1/41 (2.44%)  1
Biliary sepsis † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Diverticulitis † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Post procedural sepsis † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Sepsis † 1  2/80 (2.50%)  2 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Upper respiratory tract infection † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Nasopharyngitis † 1  1/80 (1.25%)  1 0/77 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Haematoma muscle † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Acute myeloid leukaemia † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Diffuse large B-cell lymphoma † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Nervous system disorders         
Facial paralysis † 1  0/80 (0.00%)  0 0/77 (0.00%)  0 0/39 (0.00%)  0 1/41 (2.44%)  1
Renal and urinary disorders         
Acute kidney injury † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Reproductive system and breast disorders         
Ovarian cyst † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Dyspnoea † 1  0/80 (0.00%)  0 0/77 (0.00%)  0 0/39 (0.00%)  0 1/41 (2.44%)  1
Epistaxis † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Hypersensitivity pneumonitis † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
Vascular disorders         
Deep vein thrombosis † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0
1
Term from vocabulary, MedDRA (20.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Run-in Period: Pegcetacoplan + Eculizumab Open-label Period: Pegcetacoplan RCP: Eculizumab RCP: Pegcetacoplan
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   71/80 (88.75%)      71/77 (92.21%)      36/39 (92.31%)      36/41 (87.80%)    
Blood and lymphatic system disorders         
Haemolysis † 1  1/80 (1.25%)  1 13/77 (16.88%)  14 9/39 (23.08%)  14 4/41 (9.76%)  4
Thrombocytopenia † 1  2/80 (2.50%)  2 3/77 (3.90%)  5 0/39 (0.00%)  0 2/41 (4.88%)  2
Anaemia † 1  1/80 (1.25%)  1 2/77 (2.60%)  2 5/39 (12.82%)  5 0/41 (0.00%)  0
Cardiac disorders         
Palpitations † 1  1/80 (1.25%)  2 1/77 (1.30%)  1 2/39 (5.13%)  2 0/41 (0.00%)  0
Gastrointestinal disorders         
Diarrhoea † 1  10/80 (12.50%)  11 11/77 (14.29%)  15 2/39 (5.13%)  2 9/41 (21.95%)  9
Abdominal pain † 1  2/80 (2.50%)  2 3/77 (3.90%)  3 3/39 (7.69%)  3 4/41 (9.76%)  4
Abdominal distension † 1  1/80 (1.25%)  1 4/77 (5.19%)  4 1/39 (2.56%)  1 0/41 (0.00%)  0
Nausea † 1  7/80 (8.75%)  8 2/77 (2.60%)  4 2/39 (5.13%)  2 2/41 (4.88%)  2
Vomiting † 1  1/80 (1.25%)  1 3/77 (3.90%)  3 4/39 (10.26%)  4 0/41 (0.00%)  0
Abdominal discomfort † 1  2/80 (2.50%)  2 0/77 (0.00%)  0 2/39 (5.13%)  2 2/41 (4.88%)  2
Constipation † 1  1/80 (1.25%)  1 2/77 (2.60%)  2 3/39 (7.69%)  3 0/41 (0.00%)  0
General disorders         
Injection site erythema † 1  33/80 (41.25%)  75 9/77 (11.69%)  127 0/39 (0.00%)  0 7/41 (17.07%)  44
Fatigue † 1  5/80 (6.25%)  5 8/77 (10.39%)  11 6/39 (15.38%)  7 2/41 (4.88%)  2
Pyrexia † 1  6/80 (7.50%)  6 6/77 (7.79%)  9 1/39 (2.56%)  1 1/41 (2.44%)  1
Injection site pruritus † 1  12/80 (15.00%)  14 5/77 (6.49%)  7 0/39 (0.00%)  0 1/41 (2.44%)  1
Asthenia † 1  1/80 (1.25%)  1 4/77 (5.19%)  4 5/39 (12.82%)  7 3/41 (7.32%)  3
Injection site bruising † 1  2/80 (2.50%)  3 3/77 (3.90%)  7 0/39 (0.00%)  0 2/41 (4.88%)  2
Injection site induration † 1  5/80 (6.25%)  12 5/77 (6.49%)  27 0/39 (0.00%)  0 3/41 (7.32%)  8
Injection site reaction † 1  8/80 (10.00%)  26 2/77 (2.60%)  8 0/39 (0.00%)  0 4/41 (9.76%)  56
Injection site swelling † 1  10/80 (12.50%)  18 1/77 (1.30%)  4 0/39 (0.00%)  0 4/41 (9.76%)  6
Injection site pain † 1  6/80 (7.50%)  13 4/77 (5.19%)  68 0/39 (0.00%)  0 1/41 (2.44%)  9
Vaccination site pain † 1  3/80 (3.75%)  3 0/77 (0.00%)  0 2/39 (5.13%)  2 0/41 (0.00%)  0
Hepatobiliary disorders         
Hyperbilirubinaemia † 1  0/80 (0.00%)  0 3/77 (3.90%)  3 2/39 (5.13%)  2 1/41 (2.44%)  1
Infections and infestations         
Nasopharyngitis † 1  4/80 (5.00%)  5 12/77 (15.58%)  13 2/39 (5.13%)  2 3/41 (7.32%)  3
Upper respiratory tract infection † 1  0/80 (0.00%)  0 7/77 (9.09%)  8 1/39 (2.56%)  1 1/41 (2.44%)  1
Urinary tract infection † 1  1/80 (1.25%)  1 7/77 (9.09%)  7 2/39 (5.13%)  2 0/41 (0.00%)  0
Oral herpes † 1  1/80 (1.25%)  1 6/77 (7.79%)  7 0/39 (0.00%)  0 2/41 (4.88%)  2
Sinusitis † 1  1/80 (1.25%)  1 3/77 (3.90%)  3 2/39 (5.13%)  2 1/41 (2.44%)  1
Injury, poisoning and procedural complications         
Vaccination complication † 1  2/80 (2.50%)  3 2/77 (2.60%)  2 0/39 (0.00%)  0 2/41 (4.88%)  2
Contusion † 1  3/80 (3.75%)  3 4/77 (5.19%)  4 0/39 (0.00%)  0 1/41 (2.44%)  1
Metabolism and nutrition disorders         
Decreased appetite † 1  0/80 (0.00%)  0 2/77 (2.60%)  2 2/39 (5.13%)  2 0/41 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  2/80 (2.50%)  2 6/77 (7.79%)  7 2/39 (5.13%)  2 2/41 (4.88%)  2
Pain in extremity † 1  3/80 (3.75%)  3 5/77 (6.49%)  6 2/39 (5.13%)  2 2/41 (4.88%)  5
Back pain † 1  3/80 (3.75%)  3 2/77 (2.60%)  2 4/39 (10.26%)  4 3/41 (7.32%)  4
Myalgia † 1  3/80 (3.75%)  3 4/77 (5.19%)  4 1/39 (2.56%)  3 1/41 (2.44%)  1
Nervous system disorders         
Headache † 1  10/80 (12.50%)  12 8/77 (10.39%)  13 9/39 (23.08%)  10 2/41 (4.88%)  2
Dizziness † 1  3/80 (3.75%)  3 3/77 (3.90%)  3 5/39 (12.82%)  5 1/41 (2.44%)  1
Lethargy † 1  0/80 (0.00%)  0 0/77 (0.00%)  0 2/39 (5.13%)  2 0/41 (0.00%)  0
Psychiatric disorders         
Anxiety † 1  2/80 (2.50%)  2 4/77 (5.19%)  5 2/39 (5.13%)  2 1/41 (2.44%)  1
Insomnia † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 2/39 (5.13%)  2 0/41 (0.00%)  0
Renal and urinary disorders         
Acute kidney injury † 1  0/80 (0.00%)  0 4/77 (5.19%)  4 0/39 (0.00%)  0 0/41 (0.00%)  0
Chromaturia † 1  3/80 (3.75%)  3 2/77 (2.60%)  2 2/39 (5.13%)  3 0/41 (0.00%)  0
Haemoglobinuria † 1  0/80 (0.00%)  0 1/77 (1.30%)  1 2/39 (5.13%)  2 0/41 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Cough † 1  2/80 (2.50%)  2 9/77 (11.69%)  9 1/39 (2.56%)  1 1/41 (2.44%)  1
Oropharyngeal pain † 1  0/80 (0.00%)  0 6/77 (7.79%)  7 3/39 (7.69%)  3 0/41 (0.00%)  0
Dyspnoea † 1  4/80 (5.00%)  4 2/77 (2.60%)  2 3/39 (7.69%)  4 1/41 (2.44%)  1
Skin and subcutaneous tissue disorders         
Erythema † 1  0/80 (0.00%)  0 3/77 (3.90%)  3 0/39 (0.00%)  0 2/41 (4.88%)  2
Vascular disorders         
Hypertension † 1  0/80 (0.00%)  0 3/77 (3.90%)  4 1/39 (2.56%)  1 3/41 (7.32%)  3
1
Term from vocabulary, MedDRA (20.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
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Name/Title: Apellis Clinical Trial Information Line
Organization: Apellis Pharmaceuticals, Inc
Phone: 1-833-284-6361
EMail: clinicaltrials@apellis.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03500549    
Other Study ID Numbers: APL2-302
First Submitted: April 10, 2018
First Posted: April 18, 2018
Results First Submitted: October 27, 2021
Results First Posted: March 25, 2022
Last Update Posted: March 25, 2022