Paroxysmal Nocturnal Hemoglobinuria
Conditions
Brief summary
Evaluation of the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria
Interventions
DRUGPegcetacoplan
Complement (C3) Inhibitor
DRUGSoliris
Complement (C5) Inhibitor
Sponsors
Apellis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age * Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry * On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3 months prior to the Screening Visit * Hb \<10.5 g/dL at the Screening Visit * Absolute reticulocyte count \> 1.0x ULN at the Screening Visit * Platelet count of \>50,000/mm3 at the Screening Visit * Absolute neutrophil count \>500/mm3 at the Screening Visit * Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with APL-2. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits * Women of child-bearing potential (WOCBP) must have a negative pregnancy test at the Screening and Day -28 Visit (Run-in Period) and must agree to use protocol defined methods of contraception for the duration of the study and 90 days after their last dose of study drug * Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 90 days after their last dose of study drug * Willing and able to give informed consent * Willing and able to self-administer APL-2 (administration by caregiver will be allowed) * Have a body mass index (BMI) ≤35.0 kg/m2
Exclusion criteria
* Active bacterial infection that has not resolved within 14 week of Day -28 (first dose of APL-2) * Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4 weeks prior to Screening * Hereditary complement deficiency * History of bone marrow transplantation * History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration * Participation in any other investigational drug trial or exposure to other investigational agent within 30 days or 5 half-lives (whichever is longer) * Currently breast-feeding women * Inability to cooperate or any condition that, in the opinion of the investigator, could increase the subject's risk of participating in the study or confound the outcome of the study This study includes cardiac safety evaluations. The following cardiac eligibility criteria are necessary to avoid confounding the cardiac safety outcomes: * History or family history of Long QT Syndrome or torsade de pointes, unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden death * Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class \>2 * QTcF \> 470 ms, PR \> 280 ms * Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities * Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetron or pentamidine at screening * Receiving any other QTc-prolonging drugs (see Appendix 4 in Section 19.4), at a stable dose for less than 3 weeks prior to dosing * Receiving prophylactic ciprofloxacin, erythromycin or azithromycin for less than one week prior to the first dose of study medication (must have a repeat screening ECG after one week of prophylactic antibiotics with QTcF \< 470 ms)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP | Baseline and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP | Baseline and Week 16 | 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. |
| LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP | Baseline and Week 16 | 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. |
| LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP | Baseline and Week 16 | 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. |
| Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16 | Baseline and Week 16 | Hb response was defined as an increase of at least 1 g/dL in Hb from Baseline at Week 16. Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions. |
| Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16 | Week 16 | Reticulocyte normalization was defined as the ARC being below the upper limit of the gender-specific normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 were classified as nonresponders. |
| Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16 | Week 16 | Hb normalization was defined as the Hb level being above the lower limit of the normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 are classified as nonnormalization. |
| LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP | Baseline and Week 16 | 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. |
| LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP | Baseline and Week 16 | 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. |
| LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP | Baseline and Week 16 | 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. |
| 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 | Baseline and Week 16 | 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. |
| Total Number of PRBC Units Transfused During the RCP | Day 1 to Week 16 | 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. |
| Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period | Baseline and Week 48 | 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. |
| Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP | Day 1 to Week 16 | 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. |
| Mean Change From Baseline to Week 48 in ARC During the Treatment Period | Baseline and Week 48 | 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. |
| Mean Change From Week 17 to Week 48 in ARC During the Open-label Period | Week 17 and Week 48 | 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. |
| Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period | Baseline and Week 48 | 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. |
| Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period | Week 17 and Week 48 | 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. |
| Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period | Baseline and Week 48 | 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. |
| Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period | Week 17 and Week 48 | 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. |
| Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period | Baseline and Week 48 | 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. |
| Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period | Week 17 and Week 48 | 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. |
| Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Baseline and Week 48 | 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. |
| Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Week 17 and Week 48 | 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. |
| Total Number of PRBC Units Transfused During the Open-Label Period | Week 17 to Week 48 | Number of units of PRBC transfused to subjects in the open-label period are reported. |
| Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period | Week 17 and Week 48 | 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. |
Countries
Australia, Belgium, Canada, France, Germany, Japan, Russia, South Korea, Spain, United Kingdom, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Pegcetacoplan to Pegcetacoplan During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48). | 41 |
| Eculizumab to Pegcetacoplan During the 4-week run-in period (Day -28 to ≤Day 1) all subjects received twice-weekly SC doses of pegcetacoplan 1080 mg in addition to their current dosage of eculizumab treatment. On Day 1, the subjects were randomized to receive monotherapy with their pre-screening stable dose of eculizumab via intravenous infusion every 2 weeks up to the end of the RCP (Week 16). Subjects then entered the open-label run-in period where they received pegcetacoplan 1080 mg twice-weekly in addition to eculizumab for 4 weeks (Week 17 to Week 20) before crossing over to monotherapy with SC infusions of pegcetacoplan 1080 mg twice-weekly or every 3 days up to the end of the open-label period (Week 48). | 39 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Open-label Period (Week 17 to Week 48) | Adverse Event | 3 | 7 |
| RCP (Day 1 - Week 16) | Adverse Event | 3 | 0 |
Baseline characteristics
| Characteristic | Pegcetacoplan to Pegcetacoplan | Eculizumab to Pegcetacoplan | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 7 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 32 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 32 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 6 Participants | 16 Participants |
| Number of transfusions in the last 12 months prior to Day -28 < 4 | 20 Participants | 16 Participants | 36 Participants |
| Number of transfusions in the last 12 months prior to Day -28 ≥ 4 | 21 Participants | 23 Participants | 44 Participants |
| Platelet count at screening <100,000 (count/mm^3) | 12 Participants | 9 Participants | 21 Participants |
| Platelet count at screening ≥100,000 (count/mm^3) | 29 Participants | 30 Participants | 59 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 7 Participants | 12 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Reported | 10 Participants | 6 Participants | 16 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 24 Participants | 25 Participants | 49 Participants |
| Sex: Female, Male Female | 27 Participants | 22 Participants | 49 Participants |
| Sex: Female, Male Male | 14 Participants | 17 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 80 | 1 / 77 | 0 / 39 | 0 / 41 |
| other Total, other adverse events | 71 / 80 | 71 / 77 | 36 / 39 | 36 / 41 |
| serious Total, serious adverse events | 4 / 80 | 18 / 77 | 5 / 39 | 7 / 41 |
Outcome results
Primary
Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP
Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Time frame: Baseline and Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP | 2.37 Grams per deciliter (g/dL) | Standard Error 0.363 |
| Eculizumab to Pegcetacoplan | Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP | -1.47 Grams per deciliter (g/dL) | Standard Error 0.666 |
p-value: <0.000195% CI: [2.33, 5.34]MMRM
Secondary
LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time frame: Baseline and Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP | -135.82 10^9 cells/ liter (L) | Standard Error 6.543 |
| Eculizumab to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP | 27.79 10^9 cells/ liter (L) | Standard Error 11.859 |
p-value: <0.000195% CI: [-189.91, -137.3]MMRM
Secondary
LS Mean Change From Baseline to Week 16 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Scale (QLQ-C30) Scores During the RCP
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are designated by functional scales, symptom scales, and global subject QoL/overall perceived health status. For the first 28 questions the 4 possible responses are Not at all' (1), 'A little' (2), 'Quite a bit' (3) and 'Very much' (4). For the remaining 2 questions the response is requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Time frame: Baseline and Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | 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 | Symptom Scales - Nausea and vomiting | -0.34 Score on a scale | Standard Error 1.632 |
| Pegcetacoplan to Pegcetacoplan | 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 | Global Health Status/QoL | 15.91 Score on a scale | Standard Error 3.635 |
| Pegcetacoplan to Pegcetacoplan | 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 | Symptom Scales - Pain | -0.74 Score on a scale | Standard Error 4.323 |
| Pegcetacoplan to Pegcetacoplan | 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 | Symptom Scales - Dyspnoea | -20.12 Score on a scale | Standard Error 3.488 |
| Pegcetacoplan to Pegcetacoplan | 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 | Functional Scales - Cognitive functioning | 5.76 Score on a scale | Standard Error 3.258 |
| Pegcetacoplan to Pegcetacoplan | 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 | Symptom Scales - Insomnia | -9.18 Score on a scale | Standard Error 3.955 |
| Pegcetacoplan to Pegcetacoplan | 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 | Functional Scales - Role functioning | 15.39 Score on a scale | Standard Error 3.93 |
| Pegcetacoplan to Pegcetacoplan | 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 | Symptom Scales - Appetite loss | -3.76 Score on a scale | Standard Error 3.357 |
| Pegcetacoplan to Pegcetacoplan | 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 | Functional Scales - Social functioning | 15.08 Score on a scale | Standard Error 2.946 |
| Pegcetacoplan to Pegcetacoplan | 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 | Symptom Scales - Constipation | 2.98 Score on a scale | Standard Error 3.248 |
| Pegcetacoplan to Pegcetacoplan | 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 | Functional Scales - Physical functioning | 16.92 Score on a scale | Standard Error 2.081 |
| Pegcetacoplan to Pegcetacoplan | 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 | Symptom Scales - Diarrhoea | 0.31 Score on a scale | Standard Error 3.711 |
| Pegcetacoplan to Pegcetacoplan | 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 | Symptom Scales - Fatigue | -22.93 Score on a scale | Standard Error 3.321 |
| Pegcetacoplan to Pegcetacoplan | 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 | Symptom Scales - Financial difficulties | -6.82 Score on a scale | Standard Error 3.853 |
| Pegcetacoplan to Pegcetacoplan | 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 | Functional Scales - Emotional functioning | 7.98 Score on a scale | Standard Error 3.366 |
| Eculizumab to Pegcetacoplan | 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 | Symptom Scales - Financial difficulties | 0.58 Score on a scale | Standard Error 6.297 |
| Eculizumab to Pegcetacoplan | 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 | Global Health Status/QoL | -2.71 Score on a scale | Standard Error 8.515 |
| Eculizumab to Pegcetacoplan | 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 | Functional Scales - Physical functioning | 4.06 Score on a scale | Standard Error 3.605 |
| Eculizumab to Pegcetacoplan | 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 | Functional Scales - Role functioning | -9.04 Score on a scale | Standard Error 6.954 |
| Eculizumab to Pegcetacoplan | 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 | Functional Scales - Emotional functioning | 3.86 Score on a scale | Standard Error 7.237 |
| Eculizumab to Pegcetacoplan | 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 | Functional Scales - Cognitive functioning | -3.80 Score on a scale | Standard Error 6.42 |
| Eculizumab to Pegcetacoplan | 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 | Functional Scales - Social functioning | 3.82 Score on a scale | Standard Error 6.349 |
| Eculizumab to Pegcetacoplan | 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 | Symptom Scales - Fatigue | -2.18 Score on a scale | Standard Error 6.644 |
| Eculizumab to Pegcetacoplan | 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 | Symptom Scales - Nausea and vomiting | -0.33 Score on a scale | Standard Error 3.876 |
| Eculizumab to Pegcetacoplan | 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 | Symptom Scales - Dyspnoea | -5.55 Score on a scale | Standard Error 7.019 |
| Eculizumab to Pegcetacoplan | 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 | Symptom Scales - Insomnia | -9.50 Score on a scale | Standard Error 7.09 |
| Eculizumab to Pegcetacoplan | 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 | Symptom Scales - Appetite loss | 4.19 Score on a scale | Standard Error 7.009 |
| Eculizumab to Pegcetacoplan | 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 | Symptom Scales - Constipation | 1.19 Score on a scale | Standard Error 8.129 |
| Eculizumab to Pegcetacoplan | 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 | Symptom Scales - Diarrhoea | 1.68 Score on a scale | Standard Error 8.204 |
| Eculizumab to Pegcetacoplan | 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 | Symptom Scales - Pain | 2.01 Score on a scale | Standard Error 7.841 |
Comparison: Global Health Status/QoL: Difference in LS meanp-value: 0.048695% CI: [0.12, 37.13]MMRM
Comparison: Functional Scales - Physical functioning: Difference in LS meanp-value: 0.002395% CI: [4.86, 20.86]MMRM
Comparison: Functional Scales - Role functioning: Difference in LS meanp-value: 0.002795% CI: [8.84, 40.01]MMRM
Comparison: Functional Scales - Emotional functioning: Difference in LS meanp-value: 0.601395% CI: [-11.58, 19.8]MMRM
Comparison: Functional Scales - Cognitive functioning: Difference in LS meanp-value: 0.179295% CI: [-4.52, 23.64]MMRM
Comparison: Functional Scales - Social functioning: Difference in LS meanp-value: 0.103995% CI: [-2.38, 24.92]MMRM
Comparison: Symptom Scales - Fatigue: Difference in LS meanp-value: 0.006295% CI: [-35.29, -6.19]MMRM
Comparison: Symptom Scales - Nausea and vomiting: Difference in LS meanp-value: 0.997595% CI: [-8.38, 8.35]MMRM
Comparison: Symptom Scales - Pain: Difference in LS meanp-value: 0.755495% CI: [-20.36, 14.85]MMRM
Comparison: Symptom Scales - Dyspnoea: Difference in LS meanp-value: 0.06295% CI: [-29.9, 0.76]MMRM
Comparison: Symptom Scales - Insomnia: Difference in LS meanp-value: 0.968695% CI: [-15.67, 16.3]MMRM
Comparison: Symptom Scales - Appetite loss: Difference in LS meanp-value: 0.300295% CI: [-23.23, 7.33]MMRM
Comparison: Symptom Scales - Constipation: Difference in LS meanp-value: 0.837495% CI: [-15.7, 19.29]MMRM
Comparison: Symptom Scales - Diarrhoea: Difference in LS meanp-value: 0.877595% CI: [-19.28, 16.52]MMRM
Comparison: Symptom Scales - Financial difficulties: Difference in LS meanp-value: 0.306695% CI: [-21.76, 6.95]MMRM
Secondary
LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP
The FACIT-fatigue scale version 4 is a 13-item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. A higher score corresponds to a higher quality of life (QoL). Baseline was the last available, nonmissing observation before taking the first dose of pegcetacoplan. Data collected after transfusion is excluded from analysis.
Time frame: Baseline and Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP | 9.22 Score on a scale | Standard Error 1.607 |
| Eculizumab to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP | -2.65 Score on a scale | Standard Error 2.821 |
p-value: 0.000595% CI: [5.49, 18.25]MMRM
Secondary
LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time frame: Baseline and Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP | -0.02 g/L | Standard Error 0.033 |
| Eculizumab to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP | 0.12 g/L | Standard Error 0.063 |
p-value: 0.036995% CI: [-0.28, -0.01]MMRM
Secondary
LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time frame: Baseline and Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP | -17.78 Micromole (μmol)/L | Standard Error 2.727 |
| Eculizumab to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP | 4.15 Micromole (μmol)/L | Standard Error 4.477 |
p-value: 0.000295% CI: [-32.49, -11.36]MMRM
Secondary
LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time frame: Baseline and Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP | -14.76 Units (U)/L | Standard Error 42.708 |
| Eculizumab to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP | -10.12 Units (U)/L | Standard Error 71.025 |
p-value: 0.955795% CI: [-181.3, 172.04]MMRM
Secondary
LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP
The LASA consists of 3 items, where the respondents were asked to rate their perceived level of functioning. Specific domains included activity level, ability to carry out daily activities, and an item for overall QoL. Their level of functioning was reported on a 0 to 100 scale with 0 indicates As low as could be and 100 indicates As high as could be. The combined score ranged from 0 to 300, with higher scores corresponding to a higher QoL.
Time frame: Baseline and Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP | 49.38 Score on a scale | Standard Error 10.189 |
| Eculizumab to Pegcetacoplan | LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP | -9.72 Score on a scale | Standard Error 18.988 |
p-value: 0.006995% CI: [16.88, 101.32]MMRM
Secondary
Mean Change From Baseline to Week 48 in ARC During the Treatment Period
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
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in ARC During the Treatment Period | -135.64 10^9 cells/L | Standard Deviation 67.9 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in ARC During the Treatment Period | -128.22 10^9 cells/L | Standard Deviation 59.6 |
Secondary
Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period
The FACIT-fatigue scale version 4 is a 13-item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. A higher score corresponds to a higher QoL. Baseline was the last available, nonmissing observation before taking the first dose of pegcetacoplan. Data collected after transfusion is excluded from analysis.
Time frame: Baseline and Week 48
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period | 10.14 Score on a scale | Standard Deviation 9.06 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period | 9.62 Score on a scale | Standard Deviation 10.34 |
Secondary
Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period
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
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period | 2.47 g/dL | Standard Deviation 1.72 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period | 2.93 g/dL | Standard Deviation 2.09 |
Secondary
Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period
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
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period | 58.66 Score on a scale | Standard Deviation 51.16 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period | 56.52 Score on a scale | Standard Deviation 65.55 |
Secondary
Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period
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
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period | -41.53 U/L | Standard Deviation 153.68 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period | -105.27 U/L | Standard Deviation 315.59 |
Secondary
Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are designated by functional scales, symptom scales, and global subject QoL/overall perceived health status. For the first 28 questions the 4 possible responses are 'Not at all' (1), 'A little' (2), 'Quite a bit' (3) and 'Very much' (4). For the remaining 2 questions the response is requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Time frame: Baseline and Week 48
Population: The ITT set included all randomized subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Functional Scales - Cognitive functioning | 7.78 Score on a scale | Standard Deviation 23.462 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Pain | 0.56 Score on a scale | Standard Deviation 27.849 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Functional Scales - Physical functioning | 15.33 Score on a scale | Standard Deviation 15.278 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Dyspnoea | -17.78 Score on a scale | Standard Deviation 29.985 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Functional Scales - Social functioning | 16.11 Score on a scale | Standard Deviation 24.166 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Insomnia | -6.67 Score on a scale | Standard Deviation 25.371 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Functional Scales - Emotional functioning | 10.28 Score on a scale | Standard Deviation 18.657 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Appetite loss | -7.78 Score on a scale | Standard Deviation 14.339 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Fatigue | -21.48 Score on a scale | Standard Deviation 26.733 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Constipation | -1.11 Score on a scale | Standard Deviation 22.289 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Functional Scales - Role functioning | 16.67 Score on a scale | Standard Deviation 27.334 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Diarrhoea | 1.11 Score on a scale | Standard Deviation 29.664 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Nausea and vomiting | -2.22 Score on a scale | Standard Deviation 11.357 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Financial difficulties | -15.56 Score on a scale | Standard Deviation 24.343 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Global Health Status/QoL | 18.89 Score on a scale | Standard Deviation 17.635 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Financial difficulties | -8.33 Score on a scale | Standard Deviation 19.51 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Global Health Status/QoL | 13.99 Score on a scale | Standard Deviation 22.912 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Functional Scales - Physical functioning | 10.80 Score on a scale | Standard Deviation 17.765 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Functional Scales - Role functioning | 20.11 Score on a scale | Standard Deviation 27.595 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Functional Scales - Emotional functioning | 5.36 Score on a scale | Standard Deviation 17.005 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Functional Scales - Cognitive functioning | 0.00 Score on a scale | Standard Deviation 18.703 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Functional Scales - Social functioning | 14.88 Score on a scale | Standard Deviation 22.379 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Fatigue | -23.75 Score on a scale | Standard Deviation 29.506 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Nausea and vomiting | 0.00 Score on a scale | Standard Deviation 4.454 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Pain | 3.45 Score on a scale | Standard Deviation 20.596 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Dyspnoea | -27.59 Score on a scale | Standard Deviation 33.415 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Insomnia | 0.00 Score on a scale | Standard Deviation 28.172 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Appetite loss | -3.45 Score on a scale | Standard Deviation 22.44 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Constipation | -2.38 Score on a scale | Standard Deviation 8.742 |
| Eculizumab to Pegcetacoplan | Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period | Symptom Scales - Diarrhoea | 5.95 Score on a scale | Standard Deviation 15.853 |
Secondary
Mean Change From Week 17 to Week 48 in ARC During the Open-label Period
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
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in ARC During the Open-label Period | -6.50 10^9 cells/L | Standard Deviation 26.471 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in ARC During the Open-label Period | -121.15 10^9 cells/L | Standard Deviation 70.969 |
Secondary
Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period
The FACIT-fatigue scale is a 13 item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. Higher score corresponds to a higher QoL.
Time frame: Week 17 and Week 48
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period | 1.28 Score on a scale | Standard Deviation 7.805 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period | 10.19 Score on a scale | Standard Deviation 10.973 |
Secondary
Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period
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
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period | -0.16 g/dL | Standard Deviation 1.154 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period | 2.89 g/dL | Standard Deviation 2.078 |
Secondary
Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period
The FACIT-fatigue scale is a 13 item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. Higher score corresponds to a higher QoL.
Time frame: Week 17 and Week 48
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period | 13.13 Score on a scale | Standard Deviation 46.296 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period | 62.92 Score on a scale | Standard Deviation 60.053 |
Secondary
Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period
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
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period | 8.03 U/L | Standard Deviation 129.285 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period | -46.84 U/L | Standard Deviation 292.607 |
Secondary
Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are designated by functional scales, symptom scales, and global subject QoL/overall perceived health status. For the first 28 questions the 4 possible responses are 'Not at all' (1), 'A little' (2), 'Quite a bit' (3) and 'Very much' (4). For the remaining 2 questions the response is requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Time frame: Week 17 and Week 48
Population: The ITT set included all randomized subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Functional Scales - Cognitive functioning | -2.78 Score on a scale | Standard Deviation 16.999 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Pain | -2.78 Score on a scale | Standard Deviation 23.195 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Functional Scales - Physical functioning | 0.89 Score on a scale | Standard Deviation 10.168 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Dyspnoea | 3.33 Score on a scale | Standard Deviation 25.295 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Functional Scales - Social functioning | 3.89 Score on a scale | Standard Deviation 18.919 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Insomnia | 8.89 Score on a scale | Standard Deviation 23.05 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Functional Scales - Emotional functioning | -2.22 Score on a scale | Standard Deviation 27.328 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Appetite loss | -8.89 Score on a scale | Standard Deviation 26.164 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Fatigue | -2.96 Score on a scale | Standard Deviation 20.824 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Constipation | -1.11 Score on a scale | Standard Deviation 20.498 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Functional Scales - Role functioning | 5.00 Score on a scale | Standard Deviation 20.599 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Diarrhoea | -4.44 Score on a scale | Standard Deviation 28.679 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Nausea and vomiting | -2.22 Score on a scale | Standard Deviation 5.762 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Financial difficulties | -2.22 Score on a scale | Standard Deviation 12.172 |
| Pegcetacoplan to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Global Health Status/QoL | 7.22 Score on a scale | Standard Deviation 19.664 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Financial difficulties | -2.56 Score on a scale | Standard Deviation 16.119 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Global Health Status/QoL | 23.08 Score on a scale | Standard Deviation 22.149 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Functional Scales - Physical functioning | 11.03 Score on a scale | Standard Deviation 17.173 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Functional Scales - Role functioning | 19.87 Score on a scale | Standard Deviation 22.617 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Functional Scales - Emotional functioning | 1.92 Score on a scale | Standard Deviation 13.806 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Functional Scales - Cognitive functioning | 2.56 Score on a scale | Standard Deviation 24.355 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Functional Scales - Social functioning | 12.18 Score on a scale | Standard Deviation 23.361 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Fatigue | -23.08 Score on a scale | Standard Deviation 28.79 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Nausea and vomiting | -4.49 Score on a scale | Standard Deviation 12.072 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Pain | -5.77 Score on a scale | Standard Deviation 21.051 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Dyspnoea | -19.23 Score on a scale | Standard Deviation 28.555 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Insomnia | -5.13 Score on a scale | Standard Deviation 27.797 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Appetite loss | -5.13 Score on a scale | Standard Deviation 22.494 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Constipation | -1.28 Score on a scale | Standard Deviation 11.473 |
| Eculizumab to Pegcetacoplan | Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period | Symptom Scales - Diarrhoea | 3.85 Score on a scale | Standard Deviation 27.206 |
Secondary
Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16
Hb response was defined as an increase of at least 1 g/dL in Hb from Baseline at Week 16. Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Time frame: Baseline and Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16 | 75.6 Percentage of subjects |
| Eculizumab to Pegcetacoplan | Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16 | 0.0 Percentage of subjects |
95% CI: [0.5452, 0.8039]
Secondary
Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16
Hb normalization was defined as the Hb level being above the lower limit of the normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 are classified as nonnormalization.
Time frame: Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16 | 34.1 Percentage of subjects |
| Eculizumab to Pegcetacoplan | Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16 | 0.0 Percentage of subjects |
95% CI: [0.1493, 0.4593]
Secondary
Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16
Reticulocyte normalization was defined as the ARC being below the upper limit of the gender-specific normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 were classified as nonresponders.
Time frame: Week 16
Population: The ITT set includes all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16 | 78.0 Percentage of subjects |
| Eculizumab to Pegcetacoplan | Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16 | 2.6 Percentage of subjects |
95% CI: [0.5309, 0.7968]
Secondary
Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP
Subjects who experienced more than 1 transfusion during the RCP are only counted once. Subjects who did not have a transfusion but withdrew before Week 16 were considered as having a transfusion in the analysis of transfusion avoidance.
Time frame: Day 1 to Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP | 85.4 Percentage of subjects |
| Eculizumab to Pegcetacoplan | Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP | 15.4 Percentage of subjects |
p-value: <0.000195% CI: [0.483, 0.7677]Miettinen-Nurminen
Secondary
Total Number of PRBC Units Transfused During the Open-Label Period
Number of units of PRBC transfused to subjects in the open-label period are reported.
Time frame: Week 17 to Week 48
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Total Number of PRBC Units Transfused During the Open-Label Period | 68 PRBC Units |
| Eculizumab to Pegcetacoplan | Total Number of PRBC Units Transfused During the Open-Label Period | 110 PRBC Units |
| Open-label Run-in Period: Crossover to Pegcetacoplan | Total Number of PRBC Units Transfused During the Open-Label Period | 14 PRBC Units |
Secondary
Total Number of PRBC Units Transfused During the RCP
Subjects who withdrew during the RCP before Week 16 will have their number of units of PRBC estimated from the duration they were in the study.
Time frame: Day 1 to Week 16
Population: The ITT set included all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegcetacoplan to Pegcetacoplan | Total Number of PRBC Units Transfused During the RCP | 26 PRBC units |
| Eculizumab to Pegcetacoplan | Total Number of PRBC Units Transfused During the RCP | 198 PRBC units |
p-value: <0.000195% CI: [2, 4]Wilcoxon rank-sum test