Paroxysmal Nocturnal Hemoglobinuria (PNH)
Conditions
Brief summary
The purpose of this study is to enable continued access to zilucoplan (RA101495) for patients with paroxysmal nocturnal hemoglobinuria (PNH) after they complete a zilucoplan clinical study.
Interventions
Subjects will continue to receive the final maintenance dose they were receiving in the qualifying study.
Sponsors
Ra Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completion of a qualifying Ra Pharmaceuticals sponsored zilucoplan (RA101495) PNH study * Evidence of ongoing clinical benefit in the opinion of the Investigator
Exclusion criteria
* History of meningococcal disease * Current systemic infection or suspicion of active bacterial infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | From Day 1 until the Final Study Visit (up to Month 49) | TEAEs were defined as an AE that occurs after a participant's initial treatment zilucoplan start for this study (RA101495-01.202) that was not present at the time of treatment start, or an AE that increases in severity after treatment start in this study, if the event was present at the time of treatment start. |
| Percentage of Participants With Serious TEAEs | From Day 1 until the Final Study Visit (up to Month 49) | Serious Adverse event (SAE) was defined as any untoward medical occurrence that:• results in death, • is life-threatening threatening (note that this refers to an event in which the participant was at risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death if it were more severe), • requires hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, and • results in a congenital anomaly/birth defect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49) | Serum LDH levels were measure of intravascular hemolysis. As high level of LDH in the blood was indicative of hemolysis in participants with PNH. |
| Change From Baseline in Total Bilirubin Values at Each Time Point | Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49) | Total Bilirubin was monitored for signs and symptoms of hepatic or biliary dysfunction. |
| Change From Baseline in Total Hemoglobin Values at Each Time Point | Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49) | Total Hemoglobin Values were analyzed for hematology assessments. |
| Change From Baseline in Free Hemoglobin Values at Each Time Point | Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49) | Free Hemoglobin Values were analyzed for hematology assessments. |
| Change From Baseline in Haptoglobin Values at Each Time Point | Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49) | Haptoglobin values were analyzed for hematology assessments. |
| Change From Baseline in Reticulocytes at Each Time Point | Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49) | Reticulocytes values were analyzed for hematology assessments. |
| Plasma Concentrations of RA101495 and Its Major Metabolite(s) | Predose: At Day 1 (Screening), Month 1, 2, 3, 6, 9, 12, and Final Study Visit (Month 49) | Blood samples of RA101495 (zilucoplan) and its metabolites (RA102758 and RA103488) were collected for Plasma concentration analysis. |
| Change From Baseline in Hemoglobinuria Values at Each Time Point | Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and Final Study Visit (Month 49) | Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10 where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria. |
| Time Corresponding to Cmax (Tmax) of RA101495 | At Day 1, Month 1, 2, 3, 6, 9, and 12 | tmax is the time to corresponding Cmax. |
| Area Under the Drug Concentration-time Curve (AUC0-t) of RA101495 | At Day 1, Month 1, 2, 3, 6, 9, and 12 | AUC0-t is area under the drug concentration-time curves. |
| Total Complement (CH50) Levels | At Day 1, Month 1, 2, 3, 6, 9, and 12 | Blood samples collection were planned to assess complement (CH50) levels. The planned analysis of CH50 was not performed because the CH50 assay was not able to be validated due to lack of reproducibility of the manufacturer's kits. |
| Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49) | Blood samples were collected for measurement of sRBC lysis for the Classical Complement Pathways. |
| Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49) | Blood samples were collected for measurement of membrane attack complex (MAC) by Wieslab ELISA for alternative complement pathway. |
| Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49) | Blood samples were collected for measurement of Complement component 5 (C5) levels. |
| Maximum Plasma Concentration (Cmax) of RA101495 | At Day 1, Month 1, 2, 3, 6, 9, and 12 | Cmax is the maximum plasma concentration. |
| Number of Participants With Anti-drug Antibodies (ADA) | At Day 1, Month 1, 2, 3, 6, 9, and 12 | Blood samples collection were planned to analyze for the presence/absence of ADAs to zilucoplan for immunogenicity assessments. |
Countries
Australia, Canada, Finland, Germany, Hungary, New Zealand, United Kingdom, United States
Participant flow
Recruitment details
The study started to enroll participants in July 2017 and concluded in October 2021.
Pre-assignment details
The Participant Flow refers to the All Enrolled Subjects.
Participants by arm
| Arm | Count |
|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) Cohort A (Eculizumab Naive) included all participants from study RA101495-01.201 (NCT03078582) who had not received eculizumab for treatment of paroxysmal nocturnal hemoglobinuria (PNH). Participants received a loading dose of 0.3 milligram/kilogram (mg/kg) zilucoplan administered by subcutaneous (SC) injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily. | 10 |
| Zilucoplan-Cohort B (Eculizumab Switch) Cohort B (Eculizumab Switch) included all participants from study RA101495-01.201 (NCT03078582) who had received eculizumab for treatment of PNH. Participants received a loading dose of 0.3 mg/kg zilucoplan administered by SC injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily. | 6 |
| Zilucoplan (Inadequate Responder to Eculizumab) Inadequate Responder cohort included participants from qualifying study RA101495-01.203 (NCT03030183) who had an inadequate response to eculizumab treatment for PNH. Participants received a loading dose of 0.3 mg/kg zilucoplan administered by SC injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily. | 3 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Need of transfusions and signs of hemolysis | 0 | 1 | 0 |
| Overall Study | Protocol non-compliance | 0 | 0 | 1 |
| Overall Study | Sponsor, regulatory, or EC/IRB request | 7 | 3 | 1 |
| Overall Study | Stem cell transplantation | 0 | 1 | 0 |
| Overall Study | Subject withdraws consent | 3 | 0 | 0 |
| Overall Study | Trial drug not effective | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Zilucoplan-Cohort A (Eculizumab Naïve) | Zilucoplan-Cohort B (Eculizumab Switch) | Zilucoplan (Inadequate Responder to Eculizumab) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 0 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 4 Participants | 3 Participants | 13 Participants |
| Age, Continuous | 59.6 years STANDARD_DEVIATION 14.5 | 45.0 years STANDARD_DEVIATION 23 | 35.3 years STANDARD_DEVIATION 16.3 | 51.2 years STANDARD_DEVIATION 19.4 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 10 Participants | 5 Participants | 3 Participants | 18 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 6 Participants | 1 Participants | 17 Participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 2 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 3 |
| other Total, other adverse events | 9 / 10 | 6 / 6 | 2 / 3 |
| serious Total, serious adverse events | 1 / 10 | 3 / 6 | 2 / 3 |
Outcome results
Primary
Percentage of Participants With Serious TEAEs
Serious Adverse event (SAE) was defined as any untoward medical occurrence that:• results in death, • is life-threatening threatening (note that this refers to an event in which the participant was at risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death if it were more severe), • requires hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, and • results in a congenital anomaly/birth defect.
Time frame: From Day 1 until the Final Study Visit (up to Month 49)
Population: Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Percentage of Participants With Serious TEAEs | 10.0 percentage of participants |
| Zilucoplan-Cohort B (Eculizumab Switch) | Percentage of Participants With Serious TEAEs | 50.0 percentage of participants |
| Zilucoplan (Inadequate Responder to Eculizumab) | Percentage of Participants With Serious TEAEs | 66.7 percentage of participants |
Primary
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAEs were defined as an AE that occurs after a participant's initial treatment zilucoplan start for this study (RA101495-01.202) that was not present at the time of treatment start, or an AE that increases in severity after treatment start in this study, if the event was present at the time of treatment start.
Time frame: From Day 1 until the Final Study Visit (up to Month 49)
Population: Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | 90.0 percentage of participants |
| Zilucoplan-Cohort B (Eculizumab Switch) | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | 100 percentage of participants |
| Zilucoplan (Inadequate Responder to Eculizumab) | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | 66.7 percentage of participants |
Secondary
Area Under the Drug Concentration-time Curve (AUC0-t) of RA101495
AUC0-t is area under the drug concentration-time curves.
Time frame: At Day 1, Month 1, 2, 3, 6, 9, and 12
Population: PK population included all participants in the Safety population who had at least 1 plasma sample obtained for PK assessment. As per the change in planned analyses, samples/data were not collected, and AUC0-t not calculated.
Secondary
Change From Baseline in Complement Component 5 (C5) Values at Each Time Point
Blood samples were collected for measurement of Complement component 5 (C5) levels.
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)
Population: PD population included all participants in the Safety population who had at least 1 plasma sample obtained for PD assessment. Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 3 | -24.404 ug/mL | Standard Deviation 50.084 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Final Study Visit (Month 49) | -28.663 ug/mL | Standard Deviation 46.526 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 9 | -0.019 ug/mL | Standard Deviation 53.475 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 6 | -6.823 ug/mL | Standard Deviation 44.787 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 2 | -15.914 ug/mL | Standard Deviation 32.737 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 1 | -11.231 ug/mL | Standard Deviation 24.96 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 12 | -40.591 ug/mL | Standard Deviation 34.977 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Final Study Visit (Month 49) | -19.770 ug/mL | Standard Deviation 74.604 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 1 | 20.488 ug/mL | Standard Deviation 31.024 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 2 | 17.716 ug/mL | Standard Deviation 33.125 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 3 | -2.898 ug/mL | Standard Deviation 49.747 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 6 | 9.572 ug/mL | Standard Deviation 24.927 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 9 | 1.177 ug/mL | Standard Deviation 27.654 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 12 | -23.487 ug/mL | Standard Deviation 30.911 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 1 | -27.505 ug/mL | Standard Deviation 90.092 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 9 | 89.670 ug/mL | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 2 | 16.310 ug/mL | Standard Deviation 36.077 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 12 | -24.905 ug/mL | Standard Deviation 17.685 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 6 | 91.640 ug/mL | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Month 3 | 22.355 ug/mL | Standard Deviation 19.764 |
Secondary
Change From Baseline in Free Hemoglobin Values at Each Time Point
Free Hemoglobin Values were analyzed for hematology assessments.
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Population: Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 1 | -0.20 milligrams per decilitre (mg/dL) | Standard Deviation 2.78 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 2 | -1.14 milligrams per decilitre (mg/dL) | Standard Deviation 3.04 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 3 | 1.34 milligrams per decilitre (mg/dL) | Standard Deviation 0.48 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 6 | -0.43 milligrams per decilitre (mg/dL) | Standard Deviation 1.24 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 9 | -1.10 milligrams per decilitre (mg/dL) | Standard Deviation 2.11 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 12 | -0.56 milligrams per decilitre (mg/dL) | Standard Deviation 2.8 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 15 | 3.93 milligrams per decilitre (mg/dL) | Standard Deviation 11.61 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 18 | 1.98 milligrams per decilitre (mg/dL) | Standard Deviation 3.05 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 21 | 3.15 milligrams per decilitre (mg/dL) | Standard Deviation 5.84 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 24 | 0.27 milligrams per decilitre (mg/dL) | Standard Deviation 0.35 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 30 | 0.33 milligrams per decilitre (mg/dL) | Standard Deviation 2.37 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 33 | 0.17 milligrams per decilitre (mg/dL) | Standard Deviation 2.66 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 39 | -0.60 milligrams per decilitre (mg/dL) | — |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 42 | 1.30 milligrams per decilitre (mg/dL) | — |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Final Study Visit (Month 49) | -2.70 milligrams per decilitre (mg/dL) | — |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Final Study Visit (Month 49) | -0.60 milligrams per decilitre (mg/dL) | Standard Deviation 1.13 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 12 | 0.80 milligrams per decilitre (mg/dL) | Standard Deviation 0.28 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 1 | 2.86 milligrams per decilitre (mg/dL) | Standard Deviation 4.3 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 2 | 0.48 milligrams per decilitre (mg/dL) | Standard Deviation 1.77 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 21 | -1.30 milligrams per decilitre (mg/dL) | Standard Deviation 0.85 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 3 | -0.02 milligrams per decilitre (mg/dL) | Standard Deviation 0.95 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 39 | -0.95 milligrams per decilitre (mg/dL) | Standard Deviation 0.64 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 6 | 0.55 milligrams per decilitre (mg/dL) | Standard Deviation 2.45 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 24 | -0.50 milligrams per decilitre (mg/dL) | Standard Deviation 0.99 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 9 | -1.50 milligrams per decilitre (mg/dL) | Standard Deviation 1.57 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 42 | 0.50 milligrams per decilitre (mg/dL) | Standard Deviation 3.68 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 15 | -1.35 milligrams per decilitre (mg/dL) | Standard Deviation 2.19 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 33 | 5.80 milligrams per decilitre (mg/dL) | — |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 18 | 0.77 milligrams per decilitre (mg/dL) | Standard Deviation 1.56 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 12 | 2.10 milligrams per decilitre (mg/dL) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Final Study Visit (Month 49) | -3.10 milligrams per decilitre (mg/dL) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 3 | 0.80 milligrams per decilitre (mg/dL) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 15 | 1.60 milligrams per decilitre (mg/dL) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 2 | 6.10 milligrams per decilitre (mg/dL) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 6 | 1.20 milligrams per decilitre (mg/dL) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 9 | 0.00 milligrams per decilitre (mg/dL) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Free Hemoglobin Values at Each Time Point | Month 1 | 0.80 milligrams per decilitre (mg/dL) | Standard Deviation 4.38 |
Secondary
Change From Baseline in Haptoglobin Values at Each Time Point
Haptoglobin values were analyzed for hematology assessments.
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Population: Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 42 | 0.034 g/L | Standard Deviation 0.076 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 15 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 39 | 0.020 g/L | Standard Deviation 0.045 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 3 | 0.021 g/L | Standard Deviation 0.06 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 18 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 2 | 0.053 g/L | Standard Deviation 0.16 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 9 | 0.008 g/L | Standard Deviation 0.021 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 21 | 0.030 g/L | Standard Deviation 0.079 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 45 | 0.080 g/L | Standard Deviation 0.113 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 1 | 0.032 g/L | Standard Deviation 0.097 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 24 | 0.030 g/L | Standard Deviation 0.079 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 36 | 0.036 g/L | Standard Deviation 0.08 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 27 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 12 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 30 | 0.004 g/L | Standard Deviation 0.009 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Final Study Visit (Month 49) | 0.042 g/L | Standard Deviation 0.127 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 6 | 0.031 g/L | Standard Deviation 0.088 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 33 | 0.002 g/L | Standard Deviation 0.004 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 1 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 36 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 39 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 42 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 45 | 0.000 g/L | — |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Final Study Visit (Month 49) | 0.006 g/L | Standard Deviation 0.013 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 6 | 0.036 g/L | Standard Deviation 0.08 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 9 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 2 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 12 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 33 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 15 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 18 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 3 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 21 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 24 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 27 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 30 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 18 | 0.000 g/L | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 1 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 2 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 3 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 6 | 0.020 g/L | Standard Deviation 0.028 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 9 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 12 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 15 | 0.000 g/L | Standard Deviation 0 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 24 | 0.000 g/L | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 21 | 0.000 g/L | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Month 30 | 0.000 g/L | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Haptoglobin Values at Each Time Point | Final Study Visit (Month 49) | 0.000 g/L | Standard Deviation 0 |
Secondary
Change From Baseline in Hemoglobinuria Values at Each Time Point
Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10 where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria.
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and Final Study Visit (Month 49)
Population: Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 33 | 1.4 score on a scale | Standard Deviation 0.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 2 | 0.9 score on a scale | Standard Deviation 1.4 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 3 | 0.4 score on a scale | Standard Deviation 1.2 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 6 | 0.4 score on a scale | Standard Deviation 0.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 9 | 0.4 score on a scale | Standard Deviation 0.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 12 | 0.9 score on a scale | Standard Deviation 1.4 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 15 | 0.9 score on a scale | Standard Deviation 1.1 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 18 | 0.1 score on a scale | Standard Deviation 0.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 21 | 0.7 score on a scale | Standard Deviation 1.6 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 24 | 0.6 score on a scale | Standard Deviation 1.6 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 27 | 0.7 score on a scale | Standard Deviation 1.5 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 30 | 0.6 score on a scale | Standard Deviation 1.3 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 1 | 0.1 score on a scale | Standard Deviation 1 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 36 | 1.4 score on a scale | Standard Deviation 1.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 39 | 0.4 score on a scale | Standard Deviation 1.7 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 42 | 1.0 score on a scale | Standard Deviation 1.2 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 45 | 1.0 score on a scale | Standard Deviation 1 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Final Study Visit (Month 49) | 0.4 score on a scale | Standard Deviation 1.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 21 | 1.0 score on a scale | Standard Deviation 1.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Final Study Visit (Month 49) | 0.6 score on a scale | Standard Deviation 0.9 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 3 | 0.8 score on a scale | Standard Deviation 1.3 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 45 | -1.0 score on a scale | — |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 30 | 1.5 score on a scale | Standard Deviation 2.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 6 | 0.8 score on a scale | Standard Deviation 1.3 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 24 | 0.3 score on a scale | Standard Deviation 0.6 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 18 | 0.3 score on a scale | Standard Deviation 0.6 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 9 | 1.5 score on a scale | Standard Deviation 2.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 39 | 1.0 score on a scale | Standard Deviation 1.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 42 | 1.5 score on a scale | Standard Deviation 2.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 12 | 1.0 score on a scale | Standard Deviation 1.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 33 | 1.0 score on a scale | Standard Deviation 1.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 27 | 1.5 score on a scale | Standard Deviation 2.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 1 | 0.2 score on a scale | Standard Deviation 1.5 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 15 | 1.0 score on a scale | Standard Deviation 1.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 36 | 1.5 score on a scale | Standard Deviation 2.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 2 | 0.8 score on a scale | Standard Deviation 1.3 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 12 | 1.0 score on a scale | Standard Deviation 1.4 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 15 | 1.0 score on a scale | Standard Deviation 1.4 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 18 | 0.0 score on a scale | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 21 | 0.0 score on a scale | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 24 | 0.0 score on a scale | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 1 | 1.7 score on a scale | Standard Deviation 1.5 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 27 | 0.0 score on a scale | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 2 | 1.0 score on a scale | Standard Deviation 1.4 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Final Study Visit (Month 49) | 2.5 score on a scale | Standard Deviation 3.5 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 3 | 0.0 score on a scale | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 6 | 0.0 score on a scale | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 30 | 0.0 score on a scale | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Hemoglobinuria Values at Each Time Point | Month 9 | 0.0 score on a scale | — |
Secondary
Change From Baseline in Reticulocytes at Each Time Point
Reticulocytes values were analyzed for hematology assessments.
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Population: Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study. Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 15 | -0.0264 10^12 reticulocytes (cells)/L | Standard Deviation 0.0601 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 2 | -0.0046 10^12 reticulocytes (cells)/L | Standard Deviation 0.0354 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 33 | -0.0302 10^12 reticulocytes (cells)/L | Standard Deviation 0.0446 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 18 | -0.0040 10^12 reticulocytes (cells)/L | Standard Deviation 0.0382 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 1 | 0.0104 10^12 reticulocytes (cells)/L | Standard Deviation 0.0484 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 30 | 0.0016 10^12 reticulocytes (cells)/L | Standard Deviation 0.0524 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 21 | -0.0223 10^12 reticulocytes (cells)/L | Standard Deviation 0.0554 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 6 | -0.0006 10^12 reticulocytes (cells)/L | Standard Deviation 0.0452 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 24 | -0.0123 10^12 reticulocytes (cells)/L | Standard Deviation 0.0711 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Final Study Visit (Month 49) | -0.0433 10^12 reticulocytes (cells)/L | Standard Deviation 0.048 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 27 | -0.0017 10^12 reticulocytes (cells)/L | Standard Deviation 0.0553 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 42 | -0.0270 10^12 reticulocytes (cells)/L | Standard Deviation 0.0721 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 9 | 0.0063 10^12 reticulocytes (cells)/L | Standard Deviation 0.0334 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 45 | -0.0423 10^12 reticulocytes (cells)/L | Standard Deviation 0.1189 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 39 | -0.0340 10^12 reticulocytes (cells)/L | Standard Deviation 0.086 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 12 | -0.0041 10^12 reticulocytes (cells)/L | Standard Deviation 0.0427 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 3 | -0.0249 10^12 reticulocytes (cells)/L | Standard Deviation 0.031 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Reticulocytes at Each Time Point | Month 36 | -0.0630 10^12 reticulocytes (cells)/L | Standard Deviation 0.0621 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 42 | -0.0015 10^12 reticulocytes (cells)/L | Standard Deviation 0.0078 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 1 | 0.0107 10^12 reticulocytes (cells)/L | Standard Deviation 0.0299 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 2 | -0.0046 10^12 reticulocytes (cells)/L | Standard Deviation 0.013 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 3 | -0.0112 10^12 reticulocytes (cells)/L | Standard Deviation 0.0251 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 6 | -0.0042 10^12 reticulocytes (cells)/L | Standard Deviation 0.0363 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 9 | 0.0070 10^12 reticulocytes (cells)/L | Standard Deviation 0.0171 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 12 | -0.0070 10^12 reticulocytes (cells)/L | Standard Deviation 0.0346 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 15 | -0.0343 10^12 reticulocytes (cells)/L | Standard Deviation 0.0191 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 18 | 0.0027 10^12 reticulocytes (cells)/L | Standard Deviation 0.038 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 21 | -0.0087 10^12 reticulocytes (cells)/L | Standard Deviation 0.038 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 24 | -0.0093 10^12 reticulocytes (cells)/L | Standard Deviation 0.0186 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 27 | 0.0150 10^12 reticulocytes (cells)/L | Standard Deviation 0.0127 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 30 | 0.0060 10^12 reticulocytes (cells)/L | Standard Deviation 0.0594 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 33 | -0.0093 10^12 reticulocytes (cells)/L | Standard Deviation 0.0234 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 36 | -0.0215 10^12 reticulocytes (cells)/L | Standard Deviation 0.0078 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 39 | -0.0133 10^12 reticulocytes (cells)/L | Standard Deviation 0.0291 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Month 45 | -0.0050 10^12 reticulocytes (cells)/L | — |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Reticulocytes at Each Time Point | Final Study Visit (Month 49) | -0.0333 10^12 reticulocytes (cells)/L | Standard Deviation 0.0116 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Reticulocytes at Each Time Point | Final Study Visit (Month 49) | 0.0100 10^12 reticulocytes (cells)/L | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Reticulocytes at Each Time Point | Month 9 | 0.0640 10^12 reticulocytes (cells)/L | Standard Deviation 0.0297 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Reticulocytes at Each Time Point | Month 1 | -0.0457 10^12 reticulocytes (cells)/L | Standard Deviation 0.0505 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Reticulocytes at Each Time Point | Month 6 | 0.0200 10^12 reticulocytes (cells)/L | Standard Deviation 0.0382 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Reticulocytes at Each Time Point | Month 18 | 0.0460 10^12 reticulocytes (cells)/L | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Reticulocytes at Each Time Point | Month 3 | 0.0170 10^12 reticulocytes (cells)/L | Standard Deviation 0.0113 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Reticulocytes at Each Time Point | Month 30 | 0.0300 10^12 reticulocytes (cells)/L | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Reticulocytes at Each Time Point | Month 15 | 0.0285 10^12 reticulocytes (cells)/L | Standard Deviation 0.029 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Reticulocytes at Each Time Point | Month 2 | 0.0115 10^12 reticulocytes (cells)/L | Standard Deviation 0.0049 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Reticulocytes at Each Time Point | Month 12 | 0.0240 10^12 reticulocytes (cells)/L | Standard Deviation 0.0113 |
Secondary
Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point
Serum LDH levels were measure of intravascular hemolysis. As high level of LDH in the blood was indicative of hemolysis in participants with PNH.
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Population: Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 33 | -39.0 Units per litre (U/L) | Standard Deviation 65.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 2 | 50.3 Units per litre (U/L) | Standard Deviation 156.2 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 3 | -6.5 Units per litre (U/L) | Standard Deviation 58.2 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 6 | 32.4 Units per litre (U/L) | Standard Deviation 142.5 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 9 | -18.1 Units per litre (U/L) | Standard Deviation 59.7 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 12 | -39.7 Units per litre (U/L) | Standard Deviation 54.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 15 | -24.5 Units per litre (U/L) | Standard Deviation 70.8 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 18 | -27.9 Units per litre (U/L) | Standard Deviation 54.8 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 21 | -12.0 Units per litre (U/L) | Standard Deviation 93.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 24 | -18.7 Units per litre (U/L) | Standard Deviation 53.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 27 | -14.0 Units per litre (U/L) | Standard Deviation 99.3 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 30 | -28.0 Units per litre (U/L) | Standard Deviation 36.1 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 1 | -3.7 Units per litre (U/L) | Standard Deviation 71.5 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 36 | -61.6 Units per litre (U/L) | Standard Deviation 47.1 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 39 | -78.4 Units per litre (U/L) | Standard Deviation 80.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 42 | -42.3 Units per litre (U/L) | Standard Deviation 78.3 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 45 | 27.0 Units per litre (U/L) | — |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Final Study Visit (Month 49) | 41.6 Units per litre (U/L) | Standard Deviation 303.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 33 | -16.3 Units per litre (U/L) | Standard Deviation 66.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 15 | 4.0 Units per litre (U/L) | Standard Deviation 30.4 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 45 | 53.0 Units per litre (U/L) | — |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 24 | -27.0 Units per litre (U/L) | Standard Deviation 64.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 39 | -29.7 Units per litre (U/L) | Standard Deviation 83.5 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 1 | 10.0 Units per litre (U/L) | Standard Deviation 16.4 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 27 | 58.0 Units per litre (U/L) | Standard Deviation 8.5 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 2 | -2.4 Units per litre (U/L) | Standard Deviation 22.2 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 3 | -1.6 Units per litre (U/L) | Standard Deviation 40.5 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 30 | 59.0 Units per litre (U/L) | Standard Deviation 140 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 6 | -28.4 Units per litre (U/L) | Standard Deviation 127.3 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 9 | 22.7 Units per litre (U/L) | Standard Deviation 23.6 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 42 | 35.5 Units per litre (U/L) | Standard Deviation 75.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 12 | 8.7 Units per litre (U/L) | Standard Deviation 10.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Final Study Visit (Month 49) | -93.2 Units per litre (U/L) | Standard Deviation 139.8 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 18 | 5.7 Units per litre (U/L) | Standard Deviation 56.8 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 36 | 0.5 Units per litre (U/L) | Standard Deviation 4.9 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 21 | -7.3 Units per litre (U/L) | Standard Deviation 33.5 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 15 | 174.5 Units per litre (U/L) | Standard Deviation 215.7 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 1 | 336.7 Units per litre (U/L) | Standard Deviation 636.9 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 9 | -5.0 Units per litre (U/L) | Standard Deviation 35.4 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 18 | -56.0 Units per litre (U/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 6 | -3.5 Units per litre (U/L) | Standard Deviation 12 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 2 | 676.5 Units per litre (U/L) | Standard Deviation 970.9 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 21 | 73.0 Units per litre (U/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Final Study Visit (Month 49) | 682.0 Units per litre (U/L) | Standard Deviation 548.7 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 30 | 1817.0 Units per litre (U/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 24 | -29.0 Units per litre (U/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 3 | 39.5 Units per litre (U/L) | Standard Deviation 40.3 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Month 12 | 456.0 Units per litre (U/L) | Standard Deviation 640.6 |
Secondary
Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point
Blood samples were collected for measurement of sRBC lysis for the Classical Complement Pathways.
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)
Population: PD population included all participants in the Safety population who had at least 1 plasma sample obtained for PD assessment. Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 1 | 1.378 percent lysis of sheep erythrocytes | Standard Deviation 2.277 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 2 | 1.248 percent lysis of sheep erythrocytes | Standard Deviation 1.789 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 3 | 1.256 percent lysis of sheep erythrocytes | Standard Deviation 1.799 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 6 | 1.493 percent lysis of sheep erythrocytes | Standard Deviation 2.838 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 9 | 0.683 percent lysis of sheep erythrocytes | Standard Deviation 1.055 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 12 | 0.759 percent lysis of sheep erythrocytes | Standard Deviation 0.557 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 9 | 0.757 percent lysis of sheep erythrocytes | Standard Deviation 0.673 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 1 | 0.523 percent lysis of sheep erythrocytes | Standard Deviation 0.772 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 6 | 0.458 percent lysis of sheep erythrocytes | Standard Deviation 1.657 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 3 | 0.576 percent lysis of sheep erythrocytes | Standard Deviation 0.972 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 2 | -0.308 percent lysis of sheep erythrocytes | Standard Deviation 0.452 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Final Study Visit (Month 49) | 25.230 percent lysis of sheep erythrocytes | Standard Deviation 35.2 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 12 | 0.773 percent lysis of sheep erythrocytes | Standard Deviation 0.415 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 2 | 93.870 percent lysis of sheep erythrocytes | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 3 | -2.620 percent lysis of sheep erythrocytes | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 6 | -2.300 percent lysis of sheep erythrocytes | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 12 | 8.390 percent lysis of sheep erythrocytes | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 1 | 93.870 percent lysis of sheep erythrocytes | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Month 9 | -1.410 percent lysis of sheep erythrocytes | — |
Secondary
Change From Baseline in Total Bilirubin Values at Each Time Point
Total Bilirubin was monitored for signs and symptoms of hepatic or biliary dysfunction.
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Population: Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 33 | 2.6 micromole per litre (umol/L) | Standard Deviation 5.7 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 2 | 0.1 micromole per litre (umol/L) | Standard Deviation 10.7 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 3 | 1.4 micromole per litre (umol/L) | Standard Deviation 13.7 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 6 | 4.6 micromole per litre (umol/L) | Standard Deviation 14.8 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 9 | -0.3 micromole per litre (umol/L) | Standard Deviation 7.4 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 12 | 3.9 micromole per litre (umol/L) | Standard Deviation 8.4 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 15 | -0.4 micromole per litre (umol/L) | Standard Deviation 6.4 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 18 | 2.8 micromole per litre (umol/L) | Standard Deviation 9.5 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 21 | 3.9 micromole per litre (umol/L) | Standard Deviation 8.3 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 24 | 5.1 micromole per litre (umol/L) | Standard Deviation 16 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 27 | 4.3 micromole per litre (umol/L) | Standard Deviation 12.2 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 30 | 5.8 micromole per litre (umol/L) | Standard Deviation 14.6 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 1 | -2.1 micromole per litre (umol/L) | Standard Deviation 7.7 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 36 | -3.8 micromole per litre (umol/L) | Standard Deviation 6.8 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 39 | 0.2 micromole per litre (umol/L) | Standard Deviation 3.1 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 42 | 4.8 micromole per litre (umol/L) | Standard Deviation 15.5 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 45 | 5.0 micromole per litre (umol/L) | Standard Deviation 17 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Bilirubin Values at Each Time Point | Final Study Visit (Month 49) | 8.0 micromole per litre (umol/L) | Standard Deviation 17.3 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 33 | 3.0 micromole per litre (umol/L) | Standard Deviation 2.6 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 15 | 6.0 micromole per litre (umol/L) | Standard Deviation 9.5 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 45 | -2.0 micromole per litre (umol/L) | — |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 24 | -1.3 micromole per litre (umol/L) | Standard Deviation 3.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 39 | 0.7 micromole per litre (umol/L) | Standard Deviation 4.6 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 1 | 1.7 micromole per litre (umol/L) | Standard Deviation 6.2 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 27 | -2.0 micromole per litre (umol/L) | Standard Deviation 5.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 2 | 2.0 micromole per litre (umol/L) | Standard Deviation 7.2 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 3 | 8.2 micromole per litre (umol/L) | Standard Deviation 13.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 30 | 3.0 micromole per litre (umol/L) | Standard Deviation 7.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 6 | 3.2 micromole per litre (umol/L) | Standard Deviation 7.2 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 9 | 6.0 micromole per litre (umol/L) | Standard Deviation 3 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 42 | 4.0 micromole per litre (umol/L) | Standard Deviation 15.6 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 12 | 3.0 micromole per litre (umol/L) | Standard Deviation 2 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Final Study Visit (Month 49) | 0.4 micromole per litre (umol/L) | Standard Deviation 3.9 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 18 | 2.0 micromole per litre (umol/L) | Standard Deviation 6.2 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 36 | 3.0 micromole per litre (umol/L) | Standard Deviation 0 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 21 | 2.0 micromole per litre (umol/L) | Standard Deviation 7.8 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 15 | 8.5 micromole per litre (umol/L) | Standard Deviation 9.2 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 1 | -0.3 micromole per litre (umol/L) | Standard Deviation 4.5 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 9 | -1.0 micromole per litre (umol/L) | Standard Deviation 1.4 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 18 | 3.0 micromole per litre (umol/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 6 | 2.5 micromole per litre (umol/L) | Standard Deviation 0.7 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 2 | 6.0 micromole per litre (umol/L) | Standard Deviation 2.8 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 21 | 7.0 micromole per litre (umol/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Final Study Visit (Month 49) | 0.0 micromole per litre (umol/L) | Standard Deviation 9.9 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 30 | 13.0 micromole per litre (umol/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 24 | 8.0 micromole per litre (umol/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 3 | 3.5 micromole per litre (umol/L) | Standard Deviation 2.1 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Bilirubin Values at Each Time Point | Month 12 | 2.5 micromole per litre (umol/L) | Standard Deviation 3.5 |
Secondary
Change From Baseline in Total Hemoglobin Values at Each Time Point
Total Hemoglobin Values were analyzed for hematology assessments.
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Population: Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 36 | 8.4 grams per litre (g/L) | Standard Deviation 14.2 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 15 | 3.9 grams per litre (g/L) | Standard Deviation 8.4 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 3 | 6.4 grams per litre (g/L) | Standard Deviation 6.4 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 33 | 10.0 grams per litre (g/L) | Standard Deviation 8.8 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 18 | 5.0 grams per litre (g/L) | Standard Deviation 4.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Final Study Visit (Month 49) | 1.8 grams per litre (g/L) | Standard Deviation 10.6 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 27 | 7.0 grams per litre (g/L) | Standard Deviation 10 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 21 | 6.4 grams per litre (g/L) | Standard Deviation 6.3 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 30 | 10.8 grams per litre (g/L) | Standard Deviation 7 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 24 | 7.9 grams per litre (g/L) | Standard Deviation 12.6 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 6 | 1.1 grams per litre (g/L) | Standard Deviation 11.2 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 2 | 1.1 grams per litre (g/L) | Standard Deviation 8.3 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 42 | 5.2 grams per litre (g/L) | Standard Deviation 11.2 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 9 | 2.9 grams per litre (g/L) | Standard Deviation 7.1 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 1 | 0.0 grams per litre (g/L) | Standard Deviation 11.4 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 39 | 7.6 grams per litre (g/L) | Standard Deviation 10.1 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 12 | 2.9 grams per litre (g/L) | Standard Deviation 6.1 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 45 | -1.3 grams per litre (g/L) | Standard Deviation 23.3 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 42 | 5.5 grams per litre (g/L) | Standard Deviation 0.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 1 | 0.0 grams per litre (g/L) | Standard Deviation 8.2 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 2 | -5.0 grams per litre (g/L) | Standard Deviation 9.9 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 3 | 3.0 grams per litre (g/L) | Standard Deviation 9.1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 6 | 2.0 grams per litre (g/L) | Standard Deviation 17.9 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 9 | -1.3 grams per litre (g/L) | Standard Deviation 4 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 12 | -1.7 grams per litre (g/L) | Standard Deviation 6.8 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 15 | -5.0 grams per litre (g/L) | Standard Deviation 5.3 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 18 | 1.7 grams per litre (g/L) | Standard Deviation 9.5 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 21 | -6.7 grams per litre (g/L) | Standard Deviation 7.6 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 24 | -5.0 grams per litre (g/L) | Standard Deviation 2.6 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 27 | -5.0 grams per litre (g/L) | Standard Deviation 11.3 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 30 | -4.5 grams per litre (g/L) | Standard Deviation 12 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 33 | -3.0 grams per litre (g/L) | Standard Deviation 4.4 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 36 | -2.0 grams per litre (g/L) | Standard Deviation 4.2 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 39 | 4.7 grams per litre (g/L) | Standard Deviation 2.9 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 45 | -4.0 grams per litre (g/L) | — |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Final Study Visit (Month 49) | -2.0 grams per litre (g/L) | Standard Deviation 4.1 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 12 | -5.0 grams per litre (g/L) | Standard Deviation 17 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Final Study Visit (Month 49) | -7.0 grams per litre (g/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 9 | -9.0 grams per litre (g/L) | Standard Deviation 5.7 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 21 | -1.0 grams per litre (g/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 1 | -5.7 grams per litre (g/L) | Standard Deviation 3.8 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 18 | -2.0 grams per litre (g/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 6 | -5.0 grams per litre (g/L) | Standard Deviation 17 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 3 | -3.5 grams per litre (g/L) | Standard Deviation 6.4 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 30 | -8.0 grams per litre (g/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 15 | -9.0 grams per litre (g/L) | Standard Deviation 28.3 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Total Hemoglobin Values at Each Time Point | Month 2 | -2.0 grams per litre (g/L) | Standard Deviation 11.3 |
Secondary
Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point
Blood samples were collected for measurement of membrane attack complex (MAC) by Wieslab ELISA for alternative complement pathway.
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)
Population: PD population included all participants in the Safety population who had at least 1 plasma sample obtained for PD assessment. Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 1 | 1.7 percentage of activity | Standard Deviation 5.8 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 2 | 0.1 percentage of activity | Standard Deviation 1.9 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 3 | 0.1 percentage of activity | Standard Deviation 2 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 6 | 1.0 percentage of activity | Standard Deviation 4.5 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 9 | -0.9 percentage of activity | Standard Deviation 0.8 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 12 | -1.4 percentage of activity | Standard Deviation 1.4 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 9 | -0.7 percentage of activity | Standard Deviation 0.6 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 1 | 1.0 percentage of activity | Standard Deviation 1.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 6 | -0.2 percentage of activity | Standard Deviation 1.9 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 3 | 0.0 percentage of activity | Standard Deviation 0.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 2 | -1.0 percentage of activity | Standard Deviation 1 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Final Study Visit (Month 49) | 1.0 percentage of activity | Standard Deviation 2.8 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 12 | -1.3 percentage of activity | Standard Deviation 0.6 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 2 | 51.5 percentage of activity | Standard Deviation 74.2 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 3 | 2.0 percentage of activity | Standard Deviation 1.4 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 6 | 5.0 percentage of activity | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 12 | 4.5 percentage of activity | Standard Deviation 6.4 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 1 | 48.0 percentage of activity | Standard Deviation 67.9 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Month 9 | -2.0 percentage of activity | — |
Secondary
Maximum Plasma Concentration (Cmax) of RA101495
Cmax is the maximum plasma concentration.
Time frame: At Day 1, Month 1, 2, 3, 6, 9, and 12
Population: PK population included all participants in the Safety population who had at least 1 plasma sample obtained for PK assessment. Data was not collected and analyzed for this outcome measure due to change in planned analysis.
Secondary
Number of Participants With Anti-drug Antibodies (ADA)
Blood samples collection were planned to analyze for the presence/absence of ADAs to zilucoplan for immunogenicity assessments.
Time frame: At Day 1, Month 1, 2, 3, 6, 9, and 12
Population: Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study. The planned analysis of immunogenicity (ADA) was not performed as the assay was considered not fit for purpose due to an insufficient level of drug tolerance; therefore, no samples were processed.
Secondary
Plasma Concentrations of RA101495 and Its Major Metabolite(s)
Blood samples of RA101495 (zilucoplan) and its metabolites (RA102758 and RA103488) were collected for Plasma concentration analysis.
Time frame: Predose: At Day 1 (Screening), Month 1, 2, 3, 6, 9, 12, and Final Study Visit (Month 49)
Population: Pharmacokinetic (PK) population included all participants in the Safety population who had at least 1 plasma sample obtained for PK assessment. Here, 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 12 | 1646.99 micrograms per litre (ug/L) | Standard Deviation 536 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Day 1 | 1883.49 micrograms per litre (ug/L) | Standard Deviation 593.93 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 1 | 10879.13 micrograms per litre (ug/L) | Standard Deviation 2405.19 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 9 | 1686.80 micrograms per litre (ug/L) | Standard Deviation 554.87 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 1 | 1865.06 micrograms per litre (ug/L) | Standard Deviation 594.31 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 6 | 4027.53 micrograms per litre (ug/L) | Standard Deviation 2730.92 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 6 | 1467.85 micrograms per litre (ug/L) | Standard Deviation 563.68 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 2 | 1894.86 micrograms per litre (ug/L) | Standard Deviation 608.46 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 3 | 10806.17 micrograms per litre (ug/L) | Standard Deviation 3418.92 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 3 | 1758.55 micrograms per litre (ug/L) | Standard Deviation 689.03 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 12 | 3903.41 micrograms per litre (ug/L) | Standard Deviation 1960.3 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 3 | 4191.36 micrograms per litre (ug/L) | Standard Deviation 2347.65 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 6 | 9393.42 micrograms per litre (ug/L) | Standard Deviation 2224.52 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 9 | 3132.54 micrograms per litre (ug/L) | Standard Deviation 1320.61 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 2 | 4799.29 micrograms per litre (ug/L) | Standard Deviation 3113.57 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 9 | 11848.67 micrograms per litre (ug/L) | Standard Deviation 2685.92 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Day 1 | 10999.99 micrograms per litre (ug/L) | Standard Deviation 2698.29 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 1 | 4344.99 micrograms per litre (ug/L) | Standard Deviation 2319.1 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 12 | 11495.99 micrograms per litre (ug/L) | Standard Deviation 2885.81 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 2 | 11276.17 micrograms per litre (ug/L) | Standard Deviation 2896.98 |
| Zilucoplan-Cohort A (Eculizumab Naïve) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Day 1 | 3587.68 micrograms per litre (ug/L) | Standard Deviation 1747.12 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 9 | 12282.83 micrograms per litre (ug/L) | Standard Deviation 3064.42 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Day 1 | 13616.08 micrograms per litre (ug/L) | Standard Deviation 1490.81 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 1 | 12645.38 micrograms per litre (ug/L) | Standard Deviation 1620.31 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 2 | 12220.10 micrograms per litre (ug/L) | Standard Deviation 2188.78 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 3 | 12315.28 micrograms per litre (ug/L) | Standard Deviation 2515.84 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 6 | 12218.72 micrograms per litre (ug/L) | Standard Deviation 2166.05 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 12 | 13279.97 micrograms per litre (ug/L) | Standard Deviation 2148.6 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Day 1 | 2443.62 micrograms per litre (ug/L) | Standard Deviation 560.97 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 1 | 2185.00 micrograms per litre (ug/L) | Standard Deviation 631.37 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 2 | 2090.04 micrograms per litre (ug/L) | Standard Deviation 831.8 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 3 | 1990.54 micrograms per litre (ug/L) | Standard Deviation 700.7 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 6 | 1819.20 micrograms per litre (ug/L) | Standard Deviation 613.14 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 9 | 1881.73 micrograms per litre (ug/L) | Standard Deviation 583.87 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 12 | 1954.23 micrograms per litre (ug/L) | Standard Deviation 725.54 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Day 1 | 4887.98 micrograms per litre (ug/L) | Standard Deviation 1969.22 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 1 | 4400.68 micrograms per litre (ug/L) | Standard Deviation 1823.93 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 2 | 4365.84 micrograms per litre (ug/L) | Standard Deviation 1537.67 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 3 | 4541.78 micrograms per litre (ug/L) | Standard Deviation 1706.07 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 6 | 4436.46 micrograms per litre (ug/L) | Standard Deviation 2341.16 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 9 | 4217.97 micrograms per litre (ug/L) | Standard Deviation 2015.36 |
| Zilucoplan-Cohort B (Eculizumab Switch) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 12 | 4334.47 micrograms per litre (ug/L) | Standard Deviation 1976.47 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 12 | 10.00 micrograms per litre (ug/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Final Study Visit (Month 49) | 1094.60 micrograms per litre (ug/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 12 | 12038.65 micrograms per litre (ug/L) | Standard Deviation 7934.94 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 1 | 7630.03 micrograms per litre (ug/L) | Standard Deviation 7060.56 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Day 1 | 2084.83 micrograms per litre (ug/L) | Standard Deviation 1791.35 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 9 | 15193.35 micrograms per litre (ug/L) | Standard Deviation 2756.66 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 12 | 2319.20 micrograms per litre (ug/L) | Standard Deviation 2534.84 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 1 | 1703.73 micrograms per litre (ug/L) | Standard Deviation 1605.96 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 6 | 12254.00 micrograms per litre (ug/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 9 | 2954.85 micrograms per litre (ug/L) | Standard Deviation 1754.97 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 2 | 1591.35 micrograms per litre (ug/L) | Standard Deviation 1552.03 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 3 | 12430.00 micrograms per litre (ug/L) | Standard Deviation 16.55 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Day 1 | 6976.50 micrograms per litre (ug/L) | Standard Deviation 5663.23 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 2 | 757.85 micrograms per litre (ug/L) | Standard Deviation 1018.59 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 3 | 2715.60 micrograms per litre (ug/L) | Standard Deviation 1345.48 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 3 | 1954.05 micrograms per litre (ug/L) | Standard Deviation 160.58 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 1 | 757.30 micrograms per litre (ug/L) | Standard Deviation 997.44 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Month 2 | 6865.45 micrograms per litre (ug/L) | Standard Deviation 8108.18 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 6 | 1725.50 micrograms per litre (ug/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Day 1 | 1280.07 micrograms per litre (ug/L) | Standard Deviation 1109.03 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Final Study Visit (Month 49) | 2210.00 micrograms per litre (ug/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA102758- Month 9 | 1238.55 micrograms per litre (ug/L) | Standard Deviation 166.24 |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA101495- Final Study Visit (Month 49) | 7174.20 micrograms per litre (ug/L) | — |
| Zilucoplan (Inadequate Responder to Eculizumab) | Plasma Concentrations of RA101495 and Its Major Metabolite(s) | RA103488- Month 6 | 1929.60 micrograms per litre (ug/L) | — |
Secondary
Time Corresponding to Cmax (Tmax) of RA101495
tmax is the time to corresponding Cmax.
Time frame: At Day 1, Month 1, 2, 3, 6, 9, and 12
Population: PK population included all participants in the Safety population who had at least 1 plasma sample obtained for PK assessment. Data was not collected and analyzed for this outcome measure due to change in planned analysis.
Secondary
Total Complement (CH50) Levels
Blood samples collection were planned to assess complement (CH50) levels. The planned analysis of CH50 was not performed because the CH50 assay was not able to be validated due to lack of reproducibility of the manufacturer's kits.
Time frame: At Day 1, Month 1, 2, 3, 6, 9, and 12
Population: Pharmacodynamic (PD) population included all participants in the Safety population who had at least 1 plasma sample obtained for PD assessment. Data was not collected and analyzed for this outcome measure due to change in planned analysis.