Paroxysmal Nocturnal Hemoglobinuria
Conditions
Keywords
PNH, Paroxysmal Nocturnal Hemoglobinuria, Complement inhibitor, Anemia, Hemoglobinuria, Hemolysis, Hematologic diseases, Extravascular hemolysis (EVH), Intravascular hemolysis (IVH), C3 inhibitor
Brief summary
The objectives of the study are to assess the safety, tolerability, preliminary efficacy and PK of multiple subcutaneous (SC) doses of pegcetacoplan in subjects with paroxysmal nocturnal hemoglobinuria (PNH) who have not received treatment with eculizumab in the past. An exploratory objective of the study is to assess the pharmacodynamics (PD) of multiple SC doses of pegcetacoplan when administered to PNH patients.
Detailed description
This is a Phase Ib, open-label, multiple ascending dose, pilot study in patients with PNH who have not received eculizumab (Soliris)® in the past. Two cohorts of 3 subjects are planned for evaluation. Safety will be assessed throughout the study; serial blood and urine samples will be collected for these assessments. Blood samples will be collected for the assessment of pegcetacoplan PK. Additional samples for assessment of PD will also be collected. The study will consist of four parts; * Part 1: subjects will receive pegcetacoplan for 28 days. * Part 2A: subjects may continue to receive pegcetacoplan for a further 56 days if there is evidence of perceived clinical benefit following review of available safety, PK and PD data by the investigator and sponsor * Part 2B/Part 2C: subjects may continue to receive daily pegcetacoplan treatment for up to 364 days if there is ongoing evidence of clinical benefit following review of the available safety, PK and PD data. After completion of Part 2B, subjects could continue treatment with pegcetacoplan by transitioning to an open-label extension study or Part 2C, if enrollment into the extension study was not yet available. Subjects entering Part 2C continued their pegcetacoplan dose and regimen until enrollment in the open-label extension study was available. * Part 3: Safety follow up Screening will take place within 30 days prior to the start of dosing on Day 1. If needed (see inclusion criteria), Neisseria menigitides types A, C, W, Y and B (administered as two separate vaccinations), Pneumococcal conjugate vaccine or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23, respectively), and Haemophilus influenzae Type B (Hib) vaccinations will be administered at least 14 days prior to dosing on Day 1. Subjects will be entered into Part 1 of the study on Day 1 at a time designated by the PI. During Part 1, the first 3 daily SC doses of pegcetacoplan (Day 1 to 3) as well as doses on Day 8, 15 and 22 will be administered at the clinical site. From Day 4 to Day 28 daily doses of pegcetacoplan will be administered off-site by a trained study nurse at the subject's home, workplace, or other location convenient to the subject with the exception of those days where dosing is at the clinical site. Following ongoing review of available safety, PK and PD data by the investigator and sponsor, subjects showing evidence of perceived clinical benefit may progress to Part 2A and then to Part 2B of the study and continue to receive daily doses of pegcetacoplan until Day 84 and then until Day 364. Cohort 2 will not be initiated until all subjects in Cohort 1 have reached the Day 29 visit and the SMC has reviewed emerging safety and efficacy data and determined that, at the initial dose, pegcetacoplan has an acceptable safety and tolerability profile. The planned length of participation in the study for each subject in Cohort 2 is approximately 444 days (14.5 months) from Day 30 through completion of the Day 414 Exit visit procedures). The study is planned to take place over approximately 24 months (from screening of Cohort 1 through completion of Cohort 2). This time period may change in the event that the study is terminated early, additional cohorts are enrolled, additional time is required to review safety between cohorts, or extended safety and PK sampling is added for a cohort.
Interventions
DRUGPegcetacoplan
Complement (C3) Inhibitor
Sponsors
Apellis Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female * At least 18 years old (inclusive) * Weigh \>55 kg and have a body mass index (BMI) ≤38.0 kg/m2 * Diagnosed with PNH (white blood cell (WBC) clone \>10%) * Lactose dehydrogenase (LD) ≥2 times the upper limit of normal * Last transfusion within 12 months prior to screening * Platelet count of \>30,000/mm3 * Absolute neutrophil count \>cells/500 µL * Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study * Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study * Able to provide documentary evidence of Neisseria meningitidis, Pneumococcal conjugate vaccine (multivalent) or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23) and Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day 1 dosing, OR willing to receive vaccinations against Neisseria meningitidis at least two weeks prior to dosing on Day 1 with a booster on Day 57, and PCV13 and Hib vaccines at least two weeks prior to dosing on Day 1. * Willing and able to give informed consent
Exclusion criteria
* Prior eculizumab (Soliris)® treatment * Active bacterial infection * Known infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV) * Hereditary complement deficiency * History of bone marrow transplantation * Concurrent severe aplastic anemia (SAA), defined as currently receiving immunosuppressive therapy for SAA including but not limited to cyclosporin A, tacrolimus, mycophenolate mofetil or anti-thymocyte globulin. * Participation in any other investigational drug trial or exposure to another investigational agent, device or procedure within 30 days * Evidence of QTcF prolongation defined as \>450 ms for males and \>470 ms for females at screening * Creatinine clearance (CrCl) \<50 mL/min (Cockcroft-Gault formula) at screening * Breast-feeding women * History of meningococcal disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percentage Change From Baseline in Hemoglobin at Day 365 | Baseline (Day 1) and Day 365. | Hematology assessments of hemoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Hemoglobin results were summarized for Cohort 2 only. |
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | From first dose of study drug (Day 1) up to 30 days after the last dose of study drug, up to approximately 563 days. | TEAEs were defined as adverse events (AEs) that occurred after dosing on Day 1 and up to 30 days after the last dose of study drug. A treatment-related TEAE is defined as a TEAE with a relationship to study drug of probably, possibly, unlikely, or unrelated. A serious adverse event (SAE) is defined as any AE that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; was a congenital anomaly or birth defect. TEAEs were graded according to Common Terminology Criteria for Adverse Events v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE. |
| Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Day 365 | Baseline (Day 1) and Day 365. | Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. LDH results were summarized for Cohort 2 only. |
| Mean Percentage Change From Baseline in LDH at Day 365 | Baseline (Day 1) and Day 365. | Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. LDH results were summarized for Cohort 2 only. |
| Mean Change From Baseline in Haptoglobin at Day 365 | Baseline (Day 1) and Day 365. | Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Haptoglobin results were summarized for Cohort 2 only. |
| Mean Percentage Change From Baseline in Haptoglobin at Day 365 | Baseline (Day 1) and Day 365. | Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Haptoglobin results were summarized for Cohort 2 only. |
| Mean Change From Baseline in Hemoglobin at Day 365 | Baseline (Day 1) and Day 365. | Hematology assessments of hemoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Hemoglobin results were summarized for Cohort 2 only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Day 365 | Baseline (Day 1) and Day 365. | Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. ARC results were summarized for Cohort 2 only. |
| Mean Percentage Change From Baseline in ARC at Day 365 | Baseline (Day 1) and Day 365. | Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. ARC results were summarized for Cohort 2 only. |
| Mean Change From Baseline in Total Bilirubin at Day 365 | Baseline (Day 1) and Day 365. | Serum chemistry assessments of total bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the 3 parts of the treatment period. Total bilirubin results were summarized for Cohort 2 only. |
| Mean Percentage Change From Baseline in Total Bilirubin at Day 365 | Baseline (Day 1) and Day 365. | Serum chemistry assessments of total bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the 3 parts of the treatment period. Total bilirubin results were summarized for Cohort 2 only. |
| Number of Subjects Receiving Red Blood Cell (RBC) Transfusions | From Day 1 up to Day 533. | The number of on-study RBC transfusions were monitored throughout the treatment period. |
| Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 365 | Baseline (Day 1) and Day 365. | 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). There are 13 statements with the total score ranging from 0 to 52 and higher scores indicating better quality of life. The FACIT-Fatigue Scale results were summarized for Cohort 2 only. |
Countries
Hong Kong, Malaysia, New Zealand, Thailand
Participant flow
Recruitment details
This Phase 1b, pilot study was conducted at 9 sites in 5 countries (Hong Kong, Malaysia, New Zealand, Thailand and United States) in subjects with paroxysmal nocturnal hemoglobinuria (PNH) who had not received treatment with eculizumab (Soliris®) in the past, between 01 December 2015 and 26 August 2019. A total of 22 subjects were enrolled.
Pre-assignment details
Subjects could participate in more than 1 cohort. The study consisted of 3 parts: Part 1 for Cohorts 1 and 2, Part 2 (Part 2A, Part 2B and Part 2C) for Cohort 2 only and Part 3 (safety follow-up). Cohort 2 dosing was not initiated until all subjects in Cohort 1 had completed Part 1 and review of emerging safety and efficacy data. Overall, 2 cohorts of 22 unique subjects were evaluated.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Subjects received SC injections of pegcetacoplan 180 mg/day for up to 28 days. | 3 |
| Cohort 2 Subjects received SC injections or infusions of pegcetacoplan 270 mg/day for up to 364 days if entering the open-label extension study or, if entering Part 2C, until enrollment in the open-label extension study became available. If clinically indicated on the basis of response, the pegcetacoplan dosage could be increased up to 360 mg/day. | 20 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part 1 | Withdrawal by Subject | 1 | 0 |
| Part 2A | Physician Decision | 0 | 1 |
| Part 2A | Withdrawal by Subject | 0 | 1 |
| Part 2B | Adverse Event | 0 | 1 |
| Part 2C | Adverse Event | 0 | 1 |
| Part 2C | Withdrawal by Subject | 0 | 1 |
| Part 3 (Safety Follow-up) | Other | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Cohort 1 | Cohort 2 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 3 Participants | 19 Participants |
| Race/Ethnicity, Customized Asian | 15 Participants | 0 Participants | 15 Participants |
| Race/Ethnicity, Customized Maori | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 22 Participants | 3 Participants | 19 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Female | 10 Participants | 1 Participants | 9 Participants |
| Sex: Female, Male Male | 13 Participants | 2 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 20 |
| other Total, other adverse events | 2 / 3 | 17 / 20 |
| serious Total, serious adverse events | 1 / 3 | 6 / 20 |
Outcome results
Primary
Mean Change From Baseline in Haptoglobin at Day 365
Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Haptoglobin results were summarized for Cohort 2 only.
Time frame: Baseline (Day 1) and Day 365.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug. Only subjects analyzed at Day 365 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Change From Baseline in Haptoglobin at Day 365 | 0.066 gram per liter (g/L) | Standard Deviation 0.1245 |
Primary
Mean Change From Baseline in Hemoglobin at Day 365
Hematology assessments of hemoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Hemoglobin results were summarized for Cohort 2 only.
Time frame: Baseline (Day 1) and Day 365.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug. Only subjects analyzed at Day 365 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Change From Baseline in Hemoglobin at Day 365 | 3.68 g/L | Standard Deviation 2.69 |
Primary
Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Day 365
Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. LDH results were summarized for Cohort 2 only.
Time frame: Baseline (Day 1) and Day 365.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug. Only subjects analyzed at Day 365 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Day 365 | -2105.2 units per liter (U/L) | Standard Deviation 1078.79 |
Primary
Mean Percentage Change From Baseline in Haptoglobin at Day 365
Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Haptoglobin results were summarized for Cohort 2 only.
Time frame: Baseline (Day 1) and Day 365.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug. Only subjects analyzed at Day 365 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Percentage Change From Baseline in Haptoglobin at Day 365 | 166.176 percent change | Standard Deviation 311.3656 |
Primary
Mean Percentage Change From Baseline in Hemoglobin at Day 365
Hematology assessments of hemoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Hemoglobin results were summarized for Cohort 2 only.
Time frame: Baseline (Day 1) and Day 365.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug. Only subjects analyzed at Day 365 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Percentage Change From Baseline in Hemoglobin at Day 365 | 49.86 percent change | Standard Deviation 43.254 |
Primary
Mean Percentage Change From Baseline in LDH at Day 365
Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. LDH results were summarized for Cohort 2 only.
Time frame: Baseline (Day 1) and Day 365.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug. Only subjects analyzed at Day 365 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Percentage Change From Baseline in LDH at Day 365 | -84.8 percent change | Standard Deviation 14.04 |
Primary
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity
TEAEs were defined as adverse events (AEs) that occurred after dosing on Day 1 and up to 30 days after the last dose of study drug. A treatment-related TEAE is defined as a TEAE with a relationship to study drug of probably, possibly, unlikely, or unrelated. A serious adverse event (SAE) is defined as any AE that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; was a congenital anomaly or birth defect. TEAEs were graded according to Common Terminology Criteria for Adverse Events v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.
Time frame: From first dose of study drug (Day 1) up to 30 days after the last dose of study drug, up to approximately 563 days.
Population: The safety population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Serious AEs | 1 Participants |
| Cohort 1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Treatment related TEAEs | 2 Participants |
| Cohort 1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with moderate intensity | 2 Participants |
| Cohort 1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to study drug discontinuation | 1 Participants |
| Cohort 1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to death | 0 Participants |
| Cohort 1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with life threatening intensity | 0 Participants |
| Cohort 1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with mild intensity | 0 Participants |
| Cohort 1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with severe intensity | 0 Participants |
| Cohort 1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | All TEAEs | 2 Participants |
| Cohort 2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with life threatening intensity | 1 Participants |
| Cohort 2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Serious AEs | 6 Participants |
| Cohort 2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to study drug discontinuation | 2 Participants |
| Cohort 2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with mild intensity | 3 Participants |
| Cohort 2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with moderate intensity | 8 Participants |
| Cohort 2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with severe intensity | 5 Participants |
| Cohort 2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | All TEAEs | 18 Participants |
| Cohort 2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Treatment related TEAEs | 9 Participants |
| Cohort 2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to death | 1 Participants |
Secondary
Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Day 365
Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. ARC results were summarized for Cohort 2 only.
Time frame: Baseline (Day 1) and Day 365.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug. Only subjects analyzed at Day 365 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Day 365 | -105.9 10^9 cells/L | Standard Deviation 70.28 |
Secondary
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 365
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). There are 13 statements with the total score ranging from 0 to 52 and higher scores indicating better quality of life. The FACIT-Fatigue Scale results were summarized for Cohort 2 only.
Time frame: Baseline (Day 1) and Day 365.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug. Only subjects analyzed at Day 365 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 365 | 7.1 score on a scale | Standard Deviation 11.09 |
Secondary
Mean Change From Baseline in Total Bilirubin at Day 365
Serum chemistry assessments of total bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the 3 parts of the treatment period. Total bilirubin results were summarized for Cohort 2 only.
Time frame: Baseline (Day 1) and Day 365.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug. Only subjects analyzed at Day 365 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Change From Baseline in Total Bilirubin at Day 365 | -29.9 micromole per liter (umol/L) | Standard Deviation 24.34 |
Secondary
Mean Percentage Change From Baseline in ARC at Day 365
Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. ARC results were summarized for Cohort 2 only.
Time frame: Baseline (Day 1) and Day 365.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug. Only subjects analyzed at Day 365 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Percentage Change From Baseline in ARC at Day 365 | -47.5 percent change | Standard Deviation 26.86 |
Secondary
Mean Percentage Change From Baseline in Total Bilirubin at Day 365
Serum chemistry assessments of total bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the 3 parts of the treatment period. Total bilirubin results were summarized for Cohort 2 only.
Time frame: Baseline (Day 1) and Day 365.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug. Only subjects analyzed at Day 365 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Percentage Change From Baseline in Total Bilirubin at Day 365 | -60.9 percent change | Standard Deviation 19 |
Secondary
Number of Subjects Receiving Red Blood Cell (RBC) Transfusions
The number of on-study RBC transfusions were monitored throughout the treatment period.
Time frame: From Day 1 up to Day 533.
Population: The ITT population set included all subjects eligible to receive study drug and who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Number of Subjects Receiving Red Blood Cell (RBC) Transfusions | 1 Participants |
| Cohort 2 | Number of Subjects Receiving Red Blood Cell (RBC) Transfusions | 7 Participants |