Cold Agglutinin Disease, Warm Autoimmune Hemolytic Anemia
Conditions
Brief summary
This study is to assess the safety, tolerability, preliminary efficacy, and pharmacokinetics of APL-2 in subjects with warm Autoimmune Hemolytic Anemia (wAIHA) or Cold Agglutinin Disease (CAD).
Interventions
DRUGAPL-2
Complement (C3) Inhibitor
Sponsors
Apellis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least 18 years of age. 2. Weight \< 125 Kg. 3. Subjects must have a primary diagnosis of wAIHA or CAD defined by the presence of hemolytic anemia and positive DAT for wAIHA (IgG) or CAD (C3). 4. Hemoglobin \<11 g/dL. 5. Signs of hemolysis with abnormal values by any of the hemolytic markers: 1. Increased absolute reticulocyte count (above ULN) 2. Reduced haptoglobin (below LLN) 3. Increased lactase dehydrogenase (LDH) (above ULN) 4. Increased indirect bilirubin (above ULN) 6. Women of child-bearing potential (WOCBP) (defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause) must have a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study and 60 days after their last dose of study drug. 7. Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 60 days after their last dose of study drug. 8. Able to provide documentary evidence of the following vaccinations within 2 years prior to screening: 1. Neisseria meningitides types A, C, W, Y and type B (administered as two separate vaccinations) 2. Streptococcus pneumoniae (Pneumococcal conjugate vaccine and Pneumococcal polysaccharide vaccine 23 \[PCV13 and/or PPSV23, respectively\]) 3. Haemophilus influenzae Type B (Hib) vaccine Subjects that do not have documentary evidence must be willing to receive any missing vaccinations as outlined below: 1. Neisseria meningitides types A, C, W, Y and type B must be administered prior to dosing on Day 1. A booster is administered after at least 8 weeks (Day 56; for both vaccinations). 2. Streptococcus pneumoniae PCV13 must be administered prior to dosing on Day 1 (see Section 12.2 for details). A PPSV23 booster is administered after at least 8 weeks (Day 56) 3. Haemophilus influenze Type B (Hib) must be administered prior to dosing on Day 1. 9. Willing and able to give informed consent. 10. Specific for wAIHA: Relapsed from, did not respond or relapsed, or did not tolerate, at least one prior wAIHA treatment regimen (such as prednisone, rituximab).
Exclusion criteria
1. Prior treatment with rituximab within 90 days. 2. Deficiency of iron, folic acid and vitamin B12 prior to treatment phase 3. Abnormal liver function as indicated by a direct bilirubin above normal level, and/or an AST or ALT level \> 2x upper limit of normal. Please note elevated indirect bilirubin due to hemolysis is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Part A:From first dose of study drug (Part A Day 1) up to 30days after last dose of study drug in Part A,approximately 366days Part B:From first dose of study drug (Part B Day 1) up to 56days after last dose of study drug in Part B,approximately 980days | TEAEs were defined as adverse events (AEs) that occurred after dosing on Day 1 and up to 56 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Received Red Blood Cell (RBC) Transfusions | From Day 1 up to Week 132 | The number of on-study RBC transfusions were monitored throughout the treatment period. |
| Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Weeks 48 and 132 | Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132 | 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. Mean change from baseline in ARC results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups. |
| Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 48 and 132 | Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132 | 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. Mean change from baseline in LDH results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups. |
| Mean Change From Baseline in Haptoglobin at Weeks 48 and 132 | Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132 | 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. Mean change from baseline in haptoglobin results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups. |
| Mean Change From Baseline in Hemoglobin at Weeks 48 and 132 | Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132 | 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. Mean change from baseline in hemoglobin results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups. |
| Maximum Observed Trough Serum Concentration (Ctrough,Max) of Pegcetacoplan | Pre-dose and 4 hours postdose on Day 1; pre-dose on Weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120 and 132 | Blood samples were collected for the assessment of Ctrough,max of pegcetacoplan. |
| Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 48 and 132 | Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132 | 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. Mean change from baseline in FACIT-Fatigue score results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups. |
| Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score at Weeks 48 and 132 | Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132 | The LASA consists of 5 single statements asking subjects to rate their perceived level of functioning. Specific domains include physical well-being (fatigue, activity level), emotional well-being (depression, anxiety, stress), spiritual well-being (sense of meaning), and intellectual well-being (ability to think clearly and concentrate). An item for overall quality of life is also included. Each domain scale range from 0 to 10. Where, 0 = as bad as it can be and 10 = as good as it can be. The total score ranging from 0 to 50 and higher scores indicating better quality of life. Mean change from baseline in LASA score results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups. |
| Mean Change From Baseline in Indirect Bilirubin at Weeks 48 and 132 | Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132 | Serum chemistry assessments of indirect bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Mean change from baseline in indirect bilirubin results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups. |
Countries
United States
Participant flow
Recruitment details
This Phase 2, prospective pilot study was conducted at 12 sites in Brazil and United States of America in subjects with primary diagnosis of warm antibody autoimmune hemolytic anemia (wAIHA) or cold agglutinin disease (CAD) in parallel between 27 March 2018 and 12 September 2022.
Pre-assignment details
The study consisted of 2 parts: Part A (core study phase; 12 months) and Part B (long-term extension phase; until the subject discontinued or the development program was terminated). Subjects were screened within 30 days prior to the start of dosing on day 1. A total of 24 subjects were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Cohort 1 wAIHA - 270 mg Subjects diagnosed with wAIHA received pegcetacoplan 270 mg per day SC infusion up to 12 months in Part A. | 5 |
| Part A: Cohort 1 wAIHA - 360 mg Subjects diagnosed with wAIHA received pegcetacoplan 360 mg per day SC infusion up to 12 months in Part A. | 6 |
| Part A: Cohort 2 CAD - 270 mg Subjects diagnosed with CAD received pegcetacoplan 270 per day SC infusion up to 12 months in Part A. | 7 |
| Part A: Cohort 2 CAD - 360 mg Subjects diagnosed with CAD received pegcetacoplan 360 mg per day SC infusion up to 12 months in Part A. | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Part A (Core Study Phase) | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
| Part A (Core Study Phase) | Death | 0 | 0 | 1 | 0 | 0 | 0 |
| Part A (Core Study Phase) | Lack of Efficacy | 0 | 1 | 0 | 0 | 0 | 0 |
| Part A (Core Study Phase) | Non-compliance with study drug | 0 | 0 | 1 | 0 | 0 | 0 |
| Part A (Core Study Phase) | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
| Part A (Core Study Phase) | Withdrew, per Investigator | 2 | 1 | 0 | 0 | 0 | 0 |
| Part B (Long-Term Extension Phase) | Adverse Event | 0 | 0 | 0 | 0 | 2 | 1 |
| Part B (Long-Term Extension Phase) | Death | 0 | 0 | 0 | 0 | 0 | 1 |
| Part B (Long-Term Extension Phase) | Non-Compliance With Study Drug | 0 | 0 | 0 | 0 | 0 | 1 |
| Part B (Long-Term Extension Phase) | Study Terminated By Sponsor | 0 | 0 | 0 | 0 | 3 | 5 |
| Part B (Long-Term Extension Phase) | Withdrew, Per Sponsor | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part A: Cohort 1 wAIHA - 270 mg | Part A: Cohort 1 wAIHA - 360 mg | Part A: Cohort 2 CAD - 270 mg | Part A: Cohort 2 CAD - 360 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 58.6 years STANDARD_DEVIATION 17.57 | 54.3 years STANDARD_DEVIATION 22.12 | 68.9 years STANDARD_DEVIATION 8.51 | 75.7 years STANDARD_DEVIATION 7.53 | 64.8 years STANDARD_DEVIATION 16.25 |
| Race/Ethnicity, Customized Black Or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic Or Latino | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Not Hispanic Or Latino | 2 Participants | 3 Participants | 6 Participants | 5 Participants | 16 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 6 Participants | 7 Participants | 5 Participants | 23 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 4 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 | 1 / 7 | 0 / 6 | 0 / 5 | 1 / 9 |
| other Total, other adverse events | 5 / 5 | 5 / 6 | 7 / 7 | 6 / 6 | 5 / 5 | 9 / 9 |
| serious Total, serious adverse events | 3 / 5 | 2 / 6 | 3 / 7 | 2 / 6 | 2 / 5 | 6 / 9 |
Outcome results
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 56 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: Part A:From first dose of study drug (Part A Day 1) up to 30days after last dose of study drug in Part A,approximately 366days Part B:From first dose of study drug (Part B Day 1) up to 56days after last dose of study drug in Part B,approximately 980days
Population: The Safety set included all subjects who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1 wAIHA - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Treatment related TEAEs | 4 Participants |
| Part A: Cohort 1 wAIHA - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with mild intensity | 2 Participants |
| Part A: Cohort 1 wAIHA - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with severe intensity | 3 Participants |
| Part A: Cohort 1 wAIHA - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | All TEAEs | 5 Participants |
| Part A: Cohort 1 wAIHA - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Serious AEs | 3 Participants |
| Part A: Cohort 1 wAIHA - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to study drug discontinuation | 1 Participants |
| Part A: Cohort 1 wAIHA - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to death | 0 Participants |
| Part A: Cohort 1 wAIHA - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with moderate intensity | 0 Participants |
| Part A: Cohort 1 wAIHA - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with life threatening intensity | 0 Participants |
| Part A: Cohort 1 wAIHA - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with mild intensity | 1 Participants |
| Part A: Cohort 1 wAIHA - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to study drug discontinuation | 2 Participants |
| Part A: Cohort 1 wAIHA - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with moderate intensity | 2 Participants |
| Part A: Cohort 1 wAIHA - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with life threatening intensity | 0 Participants |
| Part A: Cohort 1 wAIHA - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Serious AEs | 2 Participants |
| Part A: Cohort 1 wAIHA - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | All TEAEs | 5 Participants |
| Part A: Cohort 1 wAIHA - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with severe intensity | 2 Participants |
| Part A: Cohort 1 wAIHA - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Treatment related TEAEs | 4 Participants |
| Part A: Cohort 1 wAIHA - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to death | 0 Participants |
| Part A: Cohort 2 CAD - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with life threatening intensity | 0 Participants |
| Part A: Cohort 2 CAD - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to death | 1 Participants |
| Part A: Cohort 2 CAD - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to study drug discontinuation | 1 Participants |
| Part A: Cohort 2 CAD - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with moderate intensity | 3 Participants |
| Part A: Cohort 2 CAD - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Treatment related TEAEs | 5 Participants |
| Part A: Cohort 2 CAD - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with mild intensity | 0 Participants |
| Part A: Cohort 2 CAD - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with severe intensity | 3 Participants |
| Part A: Cohort 2 CAD - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | All TEAEs | 7 Participants |
| Part A: Cohort 2 CAD - 270 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Serious AEs | 3 Participants |
| Part A: Cohort 2 CAD - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with moderate intensity | 3 Participants |
| Part A: Cohort 2 CAD - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with severe intensity | 2 Participants |
| Part A: Cohort 2 CAD - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with life threatening intensity | 1 Participants |
| Part A: Cohort 2 CAD - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | All TEAEs | 6 Participants |
| Part A: Cohort 2 CAD - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Treatment related TEAEs | 4 Participants |
| Part A: Cohort 2 CAD - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Serious AEs | 2 Participants |
| Part A: Cohort 2 CAD - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to study drug discontinuation | 1 Participants |
| Part A: Cohort 2 CAD - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to death | 0 Participants |
| Part A: Cohort 2 CAD - 360 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with mild intensity | 0 Participants |
| Part B: Cohort 1 wAIHA - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to study drug discontinuation | 2 Participants |
| Part B: Cohort 1 wAIHA - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Treatment related TEAEs | 4 Participants |
| Part B: Cohort 1 wAIHA - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to death | 0 Participants |
| Part B: Cohort 1 wAIHA - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | All TEAEs | 5 Participants |
| Part B: Cohort 1 wAIHA - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with life threatening intensity | 0 Participants |
| Part B: Cohort 1 wAIHA - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with moderate intensity | 3 Participants |
| Part B: Cohort 1 wAIHA - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with mild intensity | 1 Participants |
| Part B: Cohort 1 wAIHA - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Serious AEs | 2 Participants |
| Part B: Cohort 1 wAIHA - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with severe intensity | 1 Participants |
| Part B: Cohort 2 CAD - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with life threatening intensity | 1 Participants |
| Part B: Cohort 2 CAD - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to study drug discontinuation | 2 Participants |
| Part B: Cohort 2 CAD - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Treatment related TEAEs | 5 Participants |
| Part B: Cohort 2 CAD - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with mild intensity | 1 Participants |
| Part B: Cohort 2 CAD - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | All TEAEs | 9 Participants |
| Part B: Cohort 2 CAD - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with moderate intensity | 2 Participants |
| Part B: Cohort 2 CAD - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs with severe intensity | 4 Participants |
| Part B: Cohort 2 CAD - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | TEAEs leading to death | 1 Participants |
| Part B: Cohort 2 CAD - 1080 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity | Serious AEs | 6 Participants |
Secondary
Maximum Observed Trough Serum Concentration (Ctrough,Max) of Pegcetacoplan
Blood samples were collected for the assessment of Ctrough,max of pegcetacoplan.
Time frame: Pre-dose and 4 hours postdose on Day 1; pre-dose on Weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120 and 132
Population: The Pharmacokinetic analysis set included all subjects in the Safety set who had at least 1 evaluable post-dose pharmacokinetic measurement that was not below the limit of quantification.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1 wAIHA - 270 mg | Maximum Observed Trough Serum Concentration (Ctrough,Max) of Pegcetacoplan | 629.6 microgram per milliliter | Standard Deviation 206.66 |
| Part A: Cohort 1 wAIHA - 360 mg | Maximum Observed Trough Serum Concentration (Ctrough,Max) of Pegcetacoplan | 679.7 microgram per milliliter | Standard Deviation 303.76 |
| Part A: Cohort 2 CAD - 270 mg | Maximum Observed Trough Serum Concentration (Ctrough,Max) of Pegcetacoplan | 661.6 microgram per milliliter | Standard Deviation 192.24 |
| Part A: Cohort 2 CAD - 360 mg | Maximum Observed Trough Serum Concentration (Ctrough,Max) of Pegcetacoplan | 807.8 microgram per milliliter | Standard Deviation 105.12 |
| Part B: Cohort 1 wAIHA - 1080 mg | Maximum Observed Trough Serum Concentration (Ctrough,Max) of Pegcetacoplan | 813.6 microgram per milliliter | Standard Deviation 260.08 |
| Part B: Cohort 2 CAD - 1080 mg | Maximum Observed Trough Serum Concentration (Ctrough,Max) of Pegcetacoplan | 795.6 microgram per milliliter | Standard Deviation 204.9 |
Secondary
Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Weeks 48 and 132
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. Mean change from baseline in ARC results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.
Time frame: Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Population: The ITT analysis set included all subjects who received at least 1 dose of study drug. Only subjects analyzed at specific timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 wAIHA - 270 mg | Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Weeks 48 and 132 | Week 48 | -145.050 10^9 cells/liter (L) | Standard Deviation 90.4181 |
| Part A: Cohort 1 wAIHA - 360 mg | Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Weeks 48 and 132 | Week 48 | -130.187 10^9 cells/liter (L) | Standard Deviation 70.4638 |
| Part A: Cohort 2 CAD - 270 mg | Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Weeks 48 and 132 | Week 48 | -73.515 10^9 cells/liter (L) | Standard Deviation 73.1983 |
| Part A: Cohort 2 CAD - 360 mg | Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Weeks 48 and 132 | Week 48 | -84.064 10^9 cells/liter (L) | Standard Deviation 46.0655 |
| Part B: Cohort 1 wAIHA - 1080 mg | Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Weeks 48 and 132 | Week 132 | 11.485 10^9 cells/liter (L) | Standard Deviation 4.9787 |
| Part B: Cohort 2 CAD - 1080 mg | Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Weeks 48 and 132 | Week 132 | 81.585 10^9 cells/liter (L) | Standard Deviation 83.479 |
Secondary
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 48 and 132
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. Mean change from baseline in FACIT-Fatigue score results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.
Time frame: Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Population: The ITT analysis set included all subjects who received at least 1 dose of study drug. Only subjects analyzed at specific timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 wAIHA - 270 mg | Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 48 and 132 | Week 48 | -3.8 score on a scale | Standard Deviation 8.38 |
| Part A: Cohort 1 wAIHA - 360 mg | Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 48 and 132 | Week 48 | 10.7 score on a scale | Standard Deviation 5.51 |
| Part A: Cohort 2 CAD - 270 mg | Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 48 and 132 | Week 48 | 0.5 score on a scale | Standard Deviation 16.33 |
| Part A: Cohort 2 CAD - 360 mg | Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 48 and 132 | Week 48 | 9.0 score on a scale | Standard Deviation 7.07 |
| Part B: Cohort 1 wAIHA - 1080 mg | Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 48 and 132 | Week 132 | -1.0 score on a scale | Standard Deviation 1.41 |
| Part B: Cohort 2 CAD - 1080 mg | Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 48 and 132 | Week 132 | 2.8 score on a scale | Standard Deviation 7.23 |
Secondary
Mean Change From Baseline in Haptoglobin at Weeks 48 and 132
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. Mean change from baseline in haptoglobin results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.
Time frame: Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Population: The ITT analysis set included all subjects who received at least 1 dose of study drug. Only subjects analyzed at specific timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 wAIHA - 270 mg | Mean Change From Baseline in Haptoglobin at Weeks 48 and 132 | Week 48 | 0.715 g/L | Standard Deviation 0.7622 |
| Part A: Cohort 1 wAIHA - 360 mg | Mean Change From Baseline in Haptoglobin at Weeks 48 and 132 | Week 48 | 0.747 g/L | Standard Deviation 0.7306 |
| Part A: Cohort 2 CAD - 270 mg | Mean Change From Baseline in Haptoglobin at Weeks 48 and 132 | Week 48 | 0.528 g/L | Standard Deviation 0.4961 |
| Part A: Cohort 2 CAD - 360 mg | Mean Change From Baseline in Haptoglobin at Weeks 48 and 132 | Week 48 | 0.172 g/L | Standard Deviation 0.3404 |
| Part B: Cohort 1 wAIHA - 1080 mg | Mean Change From Baseline in Haptoglobin at Weeks 48 and 132 | Week 132 | -0.270 g/L | Standard Deviation 0.6364 |
| Part B: Cohort 2 CAD - 1080 mg | Mean Change From Baseline in Haptoglobin at Weeks 48 and 132 | Week 132 | -0.335 g/L | Standard Deviation 0.1323 |
Secondary
Mean Change From Baseline in Hemoglobin at Weeks 48 and 132
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. Mean change from baseline in hemoglobin results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.
Time frame: Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Population: The intent-to-treat (ITT) analysis set included all subjects who received at least 1 dose of study drug. Only subjects analyzed at specific timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 wAIHA - 270 mg | Mean Change From Baseline in Hemoglobin at Weeks 48 and 132 | Week 48 | 0.38 gram per deciliter (g/dL) | Standard Deviation 2.347 |
| Part A: Cohort 1 wAIHA - 360 mg | Mean Change From Baseline in Hemoglobin at Weeks 48 and 132 | Week 48 | 1.93 gram per deciliter (g/dL) | Standard Deviation 0.874 |
| Part A: Cohort 2 CAD - 270 mg | Mean Change From Baseline in Hemoglobin at Weeks 48 and 132 | Week 48 | 1.62 gram per deciliter (g/dL) | Standard Deviation 1.522 |
| Part A: Cohort 2 CAD - 360 mg | Mean Change From Baseline in Hemoglobin at Weeks 48 and 132 | Week 48 | 2.63 gram per deciliter (g/dL) | Standard Deviation 1.694 |
| Part B: Cohort 1 wAIHA - 1080 mg | Mean Change From Baseline in Hemoglobin at Weeks 48 and 132 | Week 132 | 0.18 gram per deciliter (g/dL) | Standard Deviation 0.626 |
| Part B: Cohort 2 CAD - 1080 mg | Mean Change From Baseline in Hemoglobin at Weeks 48 and 132 | Week 132 | -0.20 gram per deciliter (g/dL) | Standard Deviation 2.029 |
Secondary
Mean Change From Baseline in Indirect Bilirubin at Weeks 48 and 132
Serum chemistry assessments of indirect bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Mean change from baseline in indirect bilirubin results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.
Time frame: Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Population: The ITT analysis set included all subjects who received at least 1 dose of study drug. Only subjects analyzed at specific timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 wAIHA - 270 mg | Mean Change From Baseline in Indirect Bilirubin at Weeks 48 and 132 | Week 48 | -10.723 micromole/L | Standard Deviation 4.2167 |
| Part A: Cohort 1 wAIHA - 360 mg | Mean Change From Baseline in Indirect Bilirubin at Weeks 48 and 132 | Week 48 | -9.697 micromole/L | Standard Deviation 5.222 |
| Part A: Cohort 2 CAD - 270 mg | Mean Change From Baseline in Indirect Bilirubin at Weeks 48 and 132 | Week 48 | -15.879 micromole/L | Standard Deviation 15.1038 |
| Part A: Cohort 2 CAD - 360 mg | Mean Change From Baseline in Indirect Bilirubin at Weeks 48 and 132 | Week 48 | -17.981 micromole/L | Standard Deviation 7.0978 |
| Part B: Cohort 1 wAIHA - 1080 mg | Mean Change From Baseline in Indirect Bilirubin at Weeks 48 and 132 | Week 132 | 0.195 micromole/L | Standard Deviation 0.2764 |
| Part B: Cohort 2 CAD - 1080 mg | Mean Change From Baseline in Indirect Bilirubin at Weeks 48 and 132 | Week 132 | 4.095 micromole/L | Standard Deviation 8.7678 |
Secondary
Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 48 and 132
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. Mean change from baseline in LDH results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.
Time frame: Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Population: The ITT analysis set included all subjects who received at least 1 dose of study drug. Only subjects analyzed at specific timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 wAIHA - 270 mg | Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 48 and 132 | Week 48 | -51.8 international units/L | Standard Deviation 39.08 |
| Part A: Cohort 1 wAIHA - 360 mg | Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 48 and 132 | Week 48 | -169.7 international units/L | Standard Deviation 212.89 |
| Part A: Cohort 2 CAD - 270 mg | Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 48 and 132 | Week 48 | -475.8 international units/L | Standard Deviation 842.43 |
| Part A: Cohort 2 CAD - 360 mg | Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 48 and 132 | Week 48 | -77.8 international units/L | Standard Deviation 73.3 |
| Part B: Cohort 1 wAIHA - 1080 mg | Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 48 and 132 | Week 132 | 1.78 international units/L | Standard Deviation 46.357 |
| Part B: Cohort 2 CAD - 1080 mg | Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 48 and 132 | Week 132 | 35.18 international units/L | Standard Deviation 82.727 |
Secondary
Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score at Weeks 48 and 132
The LASA consists of 5 single statements asking subjects to rate their perceived level of functioning. Specific domains include physical well-being (fatigue, activity level), emotional well-being (depression, anxiety, stress), spiritual well-being (sense of meaning), and intellectual well-being (ability to think clearly and concentrate). An item for overall quality of life is also included. Each domain scale range from 0 to 10. Where, 0 = as bad as it can be and 10 = as good as it can be. The total score ranging from 0 to 50 and higher scores indicating better quality of life. Mean change from baseline in LASA score results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.
Time frame: Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Population: The ITT analysis set included all subjects who received at least 1 dose of study drug. Only subjects analyzed at specific timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 wAIHA - 270 mg | Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score at Weeks 48 and 132 | Week 48 | 0.0 score on a scale | Standard Deviation 2.45 |
| Part A: Cohort 1 wAIHA - 360 mg | Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score at Weeks 48 and 132 | Week 48 | 1.3 score on a scale | Standard Deviation 4.04 |
| Part A: Cohort 2 CAD - 270 mg | Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score at Weeks 48 and 132 | Week 48 | 0.8 score on a scale | Standard Deviation 1.72 |
| Part A: Cohort 2 CAD - 360 mg | Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score at Weeks 48 and 132 | Week 48 | 1.0 score on a scale | Standard Deviation 1.15 |
| Part B: Cohort 1 wAIHA - 1080 mg | Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score at Weeks 48 and 132 | Week 132 | 0.0 score on a scale | Standard Deviation 0 |
| Part B: Cohort 2 CAD - 1080 mg | Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score at Weeks 48 and 132 | Week 132 | 0.5 score on a scale | Standard Deviation 1.73 |
Secondary
Number of Subjects Who Received 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 Week 132
Population: The ITT analysis set included all subjects who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 wAIHA - 270 mg | Number of Subjects Who Received Red Blood Cell (RBC) Transfusions | 2 Participants |
| Part A: Cohort 1 wAIHA - 360 mg | Number of Subjects Who Received Red Blood Cell (RBC) Transfusions | 2 Participants |
| Part A: Cohort 2 CAD - 270 mg | Number of Subjects Who Received Red Blood Cell (RBC) Transfusions | 2 Participants |
| Part A: Cohort 2 CAD - 360 mg | Number of Subjects Who Received Red Blood Cell (RBC) Transfusions | 1 Participants |
| Part B: Cohort 1 wAIHA - 1080 mg | Number of Subjects Who Received Red Blood Cell (RBC) Transfusions | 0 Participants |
| Part B: Cohort 2 CAD - 1080 mg | Number of Subjects Who Received Red Blood Cell (RBC) Transfusions | 3 Participants |