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Extension Study of RA101495 for Patients With PNH Who Have Completed a Zilucoplan (RA101495) Clinical Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03225287
Recruitment Status : Terminated (After careful consideration, UCB has decided to no longer pursue PNH as a potential indication for zilucoplan.)
First Posted : July 21, 2017
Results First Posted : October 27, 2022
Last Update Posted : October 27, 2022
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( Ra Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Paroxysmal Nocturnal Hemoglobinuria (PNH)
Intervention Drug: Zilucoplan (RA101495)
Enrollment 19
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.
Arm/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 10 6 3
Completed 0 0 0
Not Completed 10 6 3
Reason Not Completed
Adverse Event             0             0             1
Protocol non-compliance             0             0             1
Subject withdraws consent             3             0             0
Sponsor, regulatory, or EC/IRB request             7             3             1
Trial drug not effective             0             1             0
Need of transfusions and signs of hemolysis             0             1             0
Stem cell transplantation             0             1             0
Arm/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab) Total
Hide Arm/Group Description 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. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 10 6 3 19
Hide Baseline Analysis Population Description
Baseline Characteristics refer to the Safety Population which consisted of all participants who received at least 1 injection of zilucoplan on or after Day 1 of the extension study.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 6 participants 3 participants 19 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
  60.0%
4
  66.7%
3
 100.0%
13
  68.4%
>=65 years
4
  40.0%
2
  33.3%
0
   0.0%
6
  31.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 6 participants 3 participants 19 participants
59.6  (14.5) 45.0  (23.0) 35.3  (16.3) 51.2  (19.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 6 participants 3 participants 19 participants
Female
6
  60.0%
1
  16.7%
1
  33.3%
8
  42.1%
Male
4
  40.0%
5
  83.3%
2
  66.7%
11
  57.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 6 participants 3 participants 19 participants
Black or African American
0
   0.0%
0
   0.0%
1
  33.3%
1
   5.3%
White
10
 100.0%
6
 100.0%
1
  33.3%
17
  89.5%
Not Reported
0
   0.0%
0
   0.0%
1
  33.3%
1
   5.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 6 participants 3 participants 19 participants
Not Hispanic or Latino
10
 100.0%
5
  83.3%
3
 100.0%
18
  94.7%
Not Reported
0
   0.0%
1
  16.7%
0
   0.0%
1
   5.3%
1.Primary Outcome
Title Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study.
Arm/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 10 6 3
Measure Type: Number
Unit of Measure: percentage of participants
90.0 100 66.7
2.Primary Outcome
Title Percentage of Participants With Serious TEAEs
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study.
Arm/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 10 6 3
Measure Type: Number
Unit of Measure: percentage of participants
10.0 50.0 66.7
3.Secondary Outcome
Title Number of Participants With Anti-drug Antibodies (ADA)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 9 6 3
Mean (Standard Deviation)
Unit of Measure: Units per litre (U/L)
Month 1 Number Analyzed 9 participants 6 participants 3 participants
-3.7  (71.5) 10.0  (16.4) 336.7  (636.9)
Month 2 Number Analyzed 9 participants 5 participants 2 participants
50.3  (156.2) -2.4  (22.2) 676.5  (970.9)
Month 3 Number Analyzed 8 participants 5 participants 2 participants
-6.5  (58.2) -1.6  (40.5) 39.5  (40.3)
Month 6 Number Analyzed 8 participants 5 participants 2 participants
32.4  (142.5) -28.4  (127.3) -3.5  (12.0)
Month 9 Number Analyzed 8 participants 3 participants 2 participants
-18.1  (59.7) 22.7  (23.6) -5.0  (35.4)
Month 12 Number Analyzed 7 participants 3 participants 2 participants
-39.7  (54.9) 8.7  (10.1) 456.0  (640.6)
Month 15 Number Analyzed 6 participants 3 participants 2 participants
-24.5  (70.8) 4.0  (30.4) 174.5  (215.7)
Month 18 Number Analyzed 7 participants 3 participants 1 participants
-27.9  (54.8) 5.7  (56.8) -56.0 [1]   (NA)
Month 21 Number Analyzed 7 participants 3 participants 1 participants
-12.0  (93.9) -7.3  (33.5) 73.0 [2]   (NA)
Month 24 Number Analyzed 7 participants 3 participants 1 participants
-18.7  (53.9) -27.0  (64.1) -29.0 [2]   (NA)
Month 27 Number Analyzed 5 participants 2 participants 0 participants
-14.0  (99.3) 58.0  (8.5)
Month 30 Number Analyzed 5 participants 2 participants 1 participants
-28.0  (36.1) 59.0  (140.0) 1817.0 [2]   (NA)
Month 33 Number Analyzed 5 participants 3 participants 0 participants
-39.0  (65.9) -16.3  (66.7)
Month 36 Number Analyzed 5 participants 2 participants 0 participants
-61.6  (47.1) 0.5  (4.9)
Month 39 Number Analyzed 5 participants 3 participants 0 participants
-78.4  (80.9) -29.7  (83.5)
Month 42 Number Analyzed 4 participants 2 participants 0 participants
-42.3  (78.3) 35.5  (75.7)
Month 45 Number Analyzed 1 participants 1 participants 0 participants
27.0 [2]   (NA) 53.0 [2]   (NA)
Final Study Visit (Month 49) Number Analyzed 9 participants 5 participants 2 participants
41.6  (303.1) -93.2  (139.8) 682.0  (548.7)
[1]
Standard Deviation (SD) could not be calculated for a single participant.
[2]
SD could not be calculated for a single participant.
5.Secondary Outcome
Title Change From Baseline in Total Bilirubin Values at Each Time Point
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 9 6 3
Mean (Standard Deviation)
Unit of Measure: micromole per litre (umol/L)
Month 1 Number Analyzed 9 participants 6 participants 3 participants
-2.1  (7.7) 1.7  (6.2) -0.3  (4.5)
Month 2 Number Analyzed 9 participants 5 participants 2 participants
0.1  (10.7) 2.0  (7.2) 6.0  (2.8)
Month 3 Number Analyzed 8 participants 5 participants 2 participants
1.4  (13.7) 8.2  (13.1) 3.5  (2.1)
Month 6 Number Analyzed 8 participants 5 participants 2 participants
4.6  (14.8) 3.2  (7.2) 2.5  (0.7)
Month 9 Number Analyzed 8 participants 3 participants 2 participants
-0.3  (7.4) 6.0  (3.0) -1.0  (1.4)
Month 12 Number Analyzed 8 participants 3 participants 2 participants
3.9  (8.4) 3.0  (2.0) 2.5  (3.5)
Month 15 Number Analyzed 7 participants 3 participants 2 participants
-0.4  (6.4) 6.0  (9.5) 8.5  (9.2)
Month 18 Number Analyzed 6 participants 3 participants 1 participants
2.8  (9.5) 2.0  (6.2) 3.0 [1]   (NA)
Month 21 Number Analyzed 7 participants 3 participants 1 participants
3.9  (8.3) 2.0  (7.8) 7.0 [1]   (NA)
Month 24 Number Analyzed 7 participants 3 participants 1 participants
5.1  (16.0) -1.3  (3.1) 8.0 [1]   (NA)
Month 27 Number Analyzed 7 participants 2 participants 0 participants
4.3  (12.2) -2.0  (5.7)
Month 30 Number Analyzed 5 participants 2 participants 1 participants
5.8  (14.6) 3.0  (7.1) 13.0 [1]   (NA)
Month 33 Number Analyzed 5 participants 3 participants 0 participants
2.6  (5.7) 3.0  (2.6)
Month 36 Number Analyzed 5 participants 2 participants 0 participants
-3.8  (6.8) 3.0  (0.0)
Month 39 Number Analyzed 5 participants 3 participants 0 participants
0.2  (3.1) 0.7  (4.6)
Month 42 Number Analyzed 5 participants 2 participants 0 participants
4.8  (15.5) 4.0  (15.6)
Month 45 Number Analyzed 2 participants 1 participants 0 participants
5.0  (17.0) -2.0 [1]   (NA)
Final Study Visit (Month 49) Number Analyzed 9 participants 5 participants 2 participants
8.0  (17.3) 0.4  (3.9) 0.0  (9.9)
[1]
SD could not be calculated for a single participant.
6.Secondary Outcome
Title Change From Baseline in Total Hemoglobin Values at Each Time Point
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 9 6 3
Mean (Standard Deviation)
Unit of Measure: grams per litre (g/L)
Month 1 Number Analyzed 8 participants 6 participants 3 participants
0.0  (11.4) 0.0  (8.2) -5.7  (3.8)
Month 2 Number Analyzed 9 participants 5 participants 2 participants
1.1  (8.3) -5.0  (9.9) -2.0  (11.3)
Month 3 Number Analyzed 7 participants 5 participants 2 participants
6.4  (6.4) 3.0  (9.1) -3.5  (6.4)
Month 6 Number Analyzed 8 participants 5 participants 2 participants
1.1  (11.2) 2.0  (17.9) -5.0  (17.0)
Month 9 Number Analyzed 8 participants 3 participants 2 participants
2.9  (7.1) -1.3  (4.0) -9.0  (5.7)
Month 12 Number Analyzed 8 participants 3 participants 2 participants
2.9  (6.1) -1.7  (6.8) -5.0  (17.0)
Month 15 Number Analyzed 7 participants 3 participants 2 participants
3.9  (8.4) -5.0  (5.3) -9.0  (28.3)
Month 18 Number Analyzed 7 participants 3 participants 1 participants
5.0  (4.9) 1.7  (9.5) -2.0 [1]   (NA)
Month 21 Number Analyzed 7 participants 3 participants 1 participants
6.4  (6.3) -6.7  (7.6) -1.0 [1]   (NA)
Month 24 Number Analyzed 7 participants 3 participants 0 participants
7.9  (12.6) -5.0  (2.6)
Month 27 Number Analyzed 7 participants 2 participants 0 participants
7.0  (10.0) -5.0  (11.3)
Month 30 Number Analyzed 5 participants 2 participants 1 participants
10.8  (7.0) -4.5  (12.0) -8.0 [1]   (NA)
Month 33 Number Analyzed 5 participants 3 participants 0 participants
10.0  (8.8) -3.0  (4.4)
Month 36 Number Analyzed 5 participants 2 participants 0 participants
8.4  (14.2) -2.0  (4.2)
Month 39 Number Analyzed 5 participants 3 participants 0 participants
7.6  (10.1) 4.7  (2.9)
Month 42 Number Analyzed 5 participants 2 participants 0 participants
5.2  (11.2) 5.5  (0.7)
Month 45 Number Analyzed 3 participants 1 participants 0 participants
-1.3  (23.3) -4.0 [1]   (NA)
Final Study Visit (Month 49) Number Analyzed 9 participants 4 participants 1 participants
1.8  (10.6) -2.0  (4.1) -7.0 [1]   (NA)
[1]
SD could not be calculated for a single participant.
7.Secondary Outcome
Title Change From Baseline in Free Hemoglobin Values at Each Time Point
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 7 5 2
Mean (Standard Deviation)
Unit of Measure: milligrams per decilitre (mg/dL)
Month 1 Number Analyzed 6 participants 5 participants 2 participants
-0.20  (2.78) 2.86  (4.30) 0.80  (4.38)
Month 2 Number Analyzed 5 participants 5 participants 1 participants
-1.14  (3.04) 0.48  (1.77) 6.10 [1]   (NA)
Month 3 Number Analyzed 5 participants 5 participants 1 participants
1.34  (0.48) -0.02  (0.95) 0.80 [1]   (NA)
Month 6 Number Analyzed 6 participants 4 participants 1 participants
-0.43  (1.24) 0.55  (2.45) 1.20 [1]   (NA)
Month 9 Number Analyzed 6 participants 3 participants 1 participants
-1.10  (2.11) -1.50  (1.57) 0.00 [1]   (NA)
Month 12 Number Analyzed 7 participants 2 participants 1 participants
-0.56  (2.80) 0.80  (0.28) 2.10 [1]   (NA)
Month 15 Number Analyzed 4 participants 2 participants 1 participants
3.93  (11.61) -1.35  (2.19) 1.60 [1]   (NA)
Month 18 Number Analyzed 4 participants 3 participants 0 participants
1.98  (3.05) 0.77  (1.56)
Month 21 Number Analyzed 4 participants 2 participants 0 participants
3.15  (5.84) -1.30  (0.85)
Month 24 Number Analyzed 3 participants 2 participants 0 participants
0.27  (0.35) -0.50  (0.99)
Month 27 Number Analyzed 0 participants 0 participants 0 participants
Month 30 Number Analyzed 3 participants 0 participants 0 participants
0.33  (2.37)
Month 33 Number Analyzed 3 participants 1 participants 0 participants
0.17  (2.66) 5.80 [1]   (NA)
Month 36 Number Analyzed 0 participants 0 participants 0 participants
Month 39 Number Analyzed 1 participants 2 participants 0 participants
-0.60 [1]   (NA) -0.95  (0.64)
Month 42 Number Analyzed 1 participants 2 participants 0 participants
1.30 [1]   (NA) 0.50  (3.68)
Month 45 Number Analyzed 0 participants 0 participants 0 participants
Final Study Visit (Month 49) Number Analyzed 1 participants 2 participants 1 participants
-2.70 [1]   (NA) -0.60  (1.13) -3.10 [1]   (NA)
[1]
SD could not be calculated for a single participant.
8.Secondary Outcome
Title Change From Baseline in Haptoglobin Values at Each Time Point
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 9 6 3
Mean (Standard Deviation)
Unit of Measure: g/L
Month 1 Number Analyzed 9 participants 6 participants 3 participants
0.032  (0.097) 0.000  (0.000) 0.000  (0.000)
Month 2 Number Analyzed 9 participants 5 participants 2 participants
0.053  (0.160) 0.000  (0.000) 0.000  (0.000)
Month 3 Number Analyzed 8 participants 5 participants 2 participants
0.021  (0.060) 0.000  (0.000) 0.000  (0.000)
Month 6 Number Analyzed 8 participants 5 participants 2 participants
0.031  (0.088) 0.036  (0.080) 0.020  (0.028)
Month 9 Number Analyzed 8 participants 3 participants 2 participants
0.008  (0.021) 0.000  (0.000) 0.000  (0.000)
Month 12 Number Analyzed 8 participants 3 participants 2 participants
0.000  (0.000) 0.000  (0.000) 0.000  (0.000)
Month 15 Number Analyzed 7 participants 3 participants 2 participants
0.000  (0.000) 0.000  (0.000) 0.000  (0.000)
Month 18 Number Analyzed 7 participants 3 participants 1 participants
0.000  (0.000) 0.000  (0.000) 0.000 [1]   (NA)
Month 21 Number Analyzed 7 participants 3 participants 1 participants
0.030  (0.079) 0.000  (0.000) 0.000 [1]   (NA)
Month 24 Number Analyzed 7 participants 3 participants 1 participants
0.030  (0.079) 0.000  (0.000) 0.000 [1]   (NA)
Month 27 Number Analyzed 7 participants 2 participants 0 participants
0.000  (0.000) 0.000  (0.000)
Month 30 Number Analyzed 5 participants 2 participants 1 participants
0.004  (0.009) 0.000  (0.000) 0.000 [1]   (NA)
Month 33 Number Analyzed 5 participants 3 participants 0 participants
0.002  (0.004) 0.000  (0.000)
Month 36 Number Analyzed 5 participants 2 participants 0 participants
0.036  (0.080) 0.000  (0.000)
Month 39 Number Analyzed 5 participants 3 participants 0 participants
0.020  (0.045) 0.000  (0.000)
Month 42 Number Analyzed 5 participants 2 participants 0 participants
0.034  (0.076) 0.000  (0.000)
Month 45 Number Analyzed 2 participants 1 participants 0 participants
0.080  (0.113) 0.000 [1]   (NA)
Final Study Visit (Month 49) Number Analyzed 9 participants 5 participants 2 participants
0.042  (0.127) 0.006  (0.013) 0.000  (0.000)
[1]
SD could not be calculated for a single participant.
9.Secondary Outcome
Title Change From Baseline in Reticulocytes at Each Time Point
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 9 6 3
Mean (Standard Deviation)
Unit of Measure: 10^12 reticulocytes (cells)/L
Month 1 Number Analyzed 8 participants 6 participants 3 participants
0.0104  (0.0484) 0.0107  (0.0299) -0.0457  (0.0505)
Month 2 Number Analyzed 9 participants 5 participants 2 participants
-0.0046  (0.0354) -0.0046  (0.0130) 0.0115  (0.0049)
Month 3 Number Analyzed 7 participants 5 participants 2 participants
-0.0249  (0.0310) -0.0112  (0.0251) 0.0170  (0.0113)
Month 6 Number Analyzed 8 participants 5 participants 2 participants
-0.0006  (0.0452) -0.0042  (0.0363) 0.0200  (0.0382)
Month 9 Number Analyzed 8 participants 3 participants 2 participants
0.0063  (0.0334) 0.0070  (0.0171) 0.0640  (0.0297)
Month 12 Number Analyzed 8 participants 3 participants 2 participants
-0.0041  (0.0427) -0.0070  (0.0346) 0.0240  (0.0113)
Month 15 Number Analyzed 7 participants 3 participants 2 participants
-0.0264  (0.0601) -0.0343  (0.0191) 0.0285  (0.0290)
Month 18 Number Analyzed 7 participants 3 participants 1 participants
-0.0040  (0.0382) 0.0027  (0.0380) 0.0460 [1]   (NA)
Month 21 Number Analyzed 7 participants 3 participants 0 participants
-0.0223  (0.0554) -0.0087  (0.0380)
Month 24 Number Analyzed 7 participants 3 participants 0 participants
-0.0123  (0.0711) -0.0093  (0.0186)
Month 27 Number Analyzed 7 participants 2 participants 0 participants
-0.0017  (0.0553) 0.0150  (0.0127)
Month 30 Number Analyzed 5 participants 2 participants 1 participants
0.0016  (0.0524) 0.0060  (0.0594) 0.0300 [1]   (NA)
Month 33 Number Analyzed 5 participants 3 participants 0 participants
-0.0302  (0.0446) -0.0093  (0.0234)
Month 36 Number Analyzed 5 participants 2 participants 0 participants
-0.0630  (0.0621) -0.0215  (0.0078)
Month 39 Number Analyzed 5 participants 3 participants 0 participants
-0.0340  (0.0860) -0.0133  (0.0291)
Month 42 Number Analyzed 5 participants 2 participants 0 participants
-0.0270  (0.0721) -0.0015  (0.0078)
Month 45 Number Analyzed 3 participants 1 participants 0 participants
-0.0423  (0.1189) -0.0050 [1]   (NA)
Final Study Visit (Month 49) Number Analyzed 8 participants 4 participants 1 participants
-0.0433  (0.0480) -0.0333  (0.0116) 0.0100 [1]   (NA)
[1]
SD could not be calculated for a single participant.
10.Secondary Outcome
Title Change From Baseline in Hemoglobinuria Values at Each Time Point
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 9 6 3
Mean (Standard Deviation)
Unit of Measure: score on a scale
Month 1 Number Analyzed 8 participants 6 participants 3 participants
0.1  (1.0) 0.2  (1.5) 1.7  (1.5)
Month 2 Number Analyzed 9 participants 5 participants 2 participants
0.9  (1.4) 0.8  (1.3) 1.0  (1.4)
Month 3 Number Analyzed 8 participants 5 participants 1 participants
0.4  (1.2) 0.8  (1.3) 0.0 [1]   (NA)
Month 6 Number Analyzed 8 participants 5 participants 1 participants
0.4  (0.9) 0.8  (1.3) 0.0 [1]   (NA)
Month 9 Number Analyzed 8 participants 2 participants 1 participants
0.4  (0.9) 1.5  (2.1) 0.0 [1]   (NA)
Month 12 Number Analyzed 8 participants 3 participants 2 participants
0.9  (1.4) 1.0  (1.7) 1.0  (1.4)
Month 15 Number Analyzed 7 participants 3 participants 2 participants
0.9  (1.1) 1.0  (1.7) 1.0  (1.4)
Month 18 Number Analyzed 7 participants 3 participants 1 participants
0.1  (0.9) 0.3  (0.6) 0.0 [1]   (NA)
Month 21 Number Analyzed 7 participants 3 participants 1 participants
0.7  (1.6) 1.0  (1.7) 0.0 [1]   (NA)
Month 24 Number Analyzed 7 participants 3 participants 1 participants
0.6  (1.6) 0.3  (0.6) 0.0 [1]   (NA)
Month 27 Number Analyzed 7 participants 2 participants 1 participants
0.7  (1.5) 1.5  (2.1) 0.0 [1]   (NA)
Month 30 Number Analyzed 5 participants 2 participants 1 participants
0.6  (1.3) 1.5  (2.1) 0.0 [1]   (NA)
Month 33 Number Analyzed 5 participants 3 participants 0 participants
1.4  (0.9) 1.0  (1.7)
Month 36 Number Analyzed 5 participants 2 participants 0 participants
1.4  (1.9) 1.5  (2.1)
Month 39 Number Analyzed 5 participants 3 participants 0 participants
0.4  (1.7) 1.0  (1.7)
Month 42 Number Analyzed 5 participants 2 participants 0 participants
1.0  (1.2) 1.5  (2.1)
Month 45 Number Analyzed 3 participants 1 participants 0 participants
1.0  (1.0) -1.0 [1]   (NA)
Month 48 Number Analyzed 0 participants 0 participants 0 participants
Final Study Visit (Month 49) Number Analyzed 9 participants 5 participants 2 participants
0.4  (1.1) 0.6  (0.9) 2.5  (3.5)
[1]
SD could not be calculated for a single participant.
11.Secondary Outcome
Title Plasma Concentrations of RA101495 and Its Major Metabolite(s)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 9 6 3
Mean (Standard Deviation)
Unit of Measure: micrograms per litre (ug/L)
RA101495- Day 1 Number Analyzed 9 participants 5 participants 3 participants
10999.99  (2698.29) 13616.08  (1490.81) 6976.50  (5663.23)
RA101495- Month 1 Number Analyzed 9 participants 6 participants 3 participants
10879.13  (2405.19) 12645.38  (1620.31) 7630.03  (7060.56)
RA101495- Month 2 Number Analyzed 9 participants 5 participants 2 participants
11276.17  (2896.98) 12220.10  (2188.78) 6865.45  (8108.18)
RA101495- Month 3 Number Analyzed 8 participants 5 participants 2 participants
10806.17  (3418.92) 12315.28  (2515.84) 12430.00  (16.55)
RA101495- Month 6 Number Analyzed 6 participants 5 participants 1 participants
9393.42  (2224.52) 12218.72  (2166.05) 12254.00 [1]   (NA)
RA101495- Month 9 Number Analyzed 7 participants 3 participants 2 participants
11848.67  (2685.92) 12282.83  (3064.42) 15193.35  (2756.66)
RA101495- Month 12 Number Analyzed 8 participants 3 participants 2 participants
11495.99  (2885.81) 13279.97  (2148.60) 12038.65  (7934.94)
RA101495- Final Study Visit (Month 49) Number Analyzed 0 participants 0 participants 1 participants
7174.20 [1]   (NA)
RA102758- Day 1 Number Analyzed 9 participants 5 participants 3 participants
1883.49  (593.93) 2443.62  (560.97) 1280.07  (1109.03)
RA102758- Month 1 Number Analyzed 9 participants 6 participants 3 participants
1865.06  (594.31) 2185.00  (631.37) 757.30  (997.44)
RA102758- Month 2 Number Analyzed 9 participants 5 participants 2 participants
1894.86  (608.46) 2090.04  (831.80) 757.85  (1018.59)
RA102758- Month 3 Number Analyzed 8 participants 5 participants 2 participants
1758.55  (689.03) 1990.54  (700.70) 1954.05  (160.58)
RA102758- Month 6 Number Analyzed 6 participants 5 participants 1 participants
1467.85  (563.68) 1819.20  (613.14) 1725.50 [1]   (NA)
RA102758- Month 9 Number Analyzed 7 participants 3 participants 2 participants
1686.80  (554.87) 1881.73  (583.87) 1238.55  (166.24)
RA102758- Month 12 Number Analyzed 8 participants 3 participants 1 participants
1646.99  (536.00) 1954.23  (725.54) 10.00 [1]   (NA)
RA102758- Final Study Visit (Month 49) Number Analyzed 0 participants 0 participants 1 participants
1094.60 [1]   (NA)
RA103488- Day 1 Number Analyzed 9 participants 5 participants 3 participants
3587.68  (1747.12) 4887.98  (1969.22) 2084.83  (1791.35)
RA103488- Month 1 Number Analyzed 9 participants 6 participants 3 participants
4344.99  (2319.10) 4400.68  (1823.93) 1703.73  (1605.96)
RA103488- Month 2 Number Analyzed 9 participants 5 participants 2 participants
4799.29  (3113.57) 4365.84  (1537.67) 1591.35  (1552.03)
RA103488- Month 3 Number Analyzed 8 participants 5 participants 2 participants
4191.36  (2347.65) 4541.78  (1706.07) 2715.60  (1345.48)
RA103488- Month 6 Number Analyzed 6 participants 5 participants 1 participants
4027.53  (2730.92) 4436.46  (2341.16) 1929.60 [1]   (NA)
RA103488- Month 9 Number Analyzed 7 participants 3 participants 2 participants
3132.54  (1320.61) 4217.97  (2015.36) 2954.85  (1754.97)
RA103488- Month 12 Number Analyzed 8 participants 3 participants 2 participants
3903.41  (1960.30) 4334.47  (1976.47) 2319.20  (2534.84)
RA103488- Final Study Visit (Month 49) Number Analyzed 0 participants 0 participants 1 participants
2210.00 [1]   (NA)
[1]
SD could not be calculated for a single participant.
12.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of RA101495
Hide Description Cmax is the maximum plasma concentration.
Time Frame At Day 1, Month 1, 2, 3, 6, 9, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Time Corresponding to Cmax (Tmax) of RA101495
Hide Description tmax is the time to corresponding Cmax.
Time Frame At Day 1, Month 1, 2, 3, 6, 9, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title Area Under the Drug Concentration-time Curve (AUC0-t) of RA101495
Hide Description AUC0-t is area under the drug concentration-time curves.
Time Frame At Day 1, Month 1, 2, 3, 6, 9, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Total Complement (CH50) Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
16.Secondary Outcome
Title Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 9 6 1
Mean (Standard Deviation)
Unit of Measure: percent lysis of sheep erythrocytes
Month 1 Number Analyzed 9 participants 6 participants 1 participants
1.378  (2.277) 0.523  (0.772) 93.870 [1]   (NA)
Month 2 Number Analyzed 9 participants 5 participants 1 participants
1.248  (1.789) -0.308  (0.452) 93.870 [1]   (NA)
Month 3 Number Analyzed 8 participants 5 participants 1 participants
1.256  (1.799) 0.576  (0.972) -2.620 [1]   (NA)
Month 6 Number Analyzed 6 participants 5 participants 1 participants
1.493  (2.838) 0.458  (1.657) -2.300 [1]   (NA)
Month 9 Number Analyzed 7 participants 3 participants 1 participants
0.683  (1.055) 0.757  (0.673) -1.410 [1]   (NA)
Month 12 Number Analyzed 8 participants 3 participants 1 participants
0.759  (0.557) 0.773  (0.415) 8.390 [1]   (NA)
Final Study Visit (Month 49) Number Analyzed 0 participants 2 participants 0 participants
25.230  (35.200)
[1]
SD could not be calculated for a single participant.
17.Secondary Outcome
Title Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 9 6 2
Mean (Standard Deviation)
Unit of Measure: percentage of activity
Month 1 Number Analyzed 9 participants 6 participants 2 participants
1.7  (5.8) 1.0  (1.7) 48.0  (67.9)
Month 2 Number Analyzed 9 participants 5 participants 2 participants
0.1  (1.9) -1.0  (1.0) 51.5  (74.2)
Month 3 Number Analyzed 8 participants 5 participants 2 participants
0.1  (2.0) 0.0  (0.7) 2.0  (1.4)
Month 6 Number Analyzed 6 participants 5 participants 1 participants
1.0  (4.5) -0.2  (1.9) 5.0 [1]   (NA)
Month 9 Number Analyzed 8 participants 3 participants 1 participants
-0.9  (0.8) -0.7  (0.6) -2.0 [1]   (NA)
Month 12 Number Analyzed 8 participants 3 participants 2 participants
-1.4  (1.4) -1.3  (0.6) 4.5  (6.4)
Final Study Visit (Month 49) Number Analyzed 0 participants 2 participants 0 participants
1.0  (2.8)
[1]
SD could not be calculated for a single participant.
18.Secondary Outcome
Title Change From Baseline in Complement Component 5 (C5) Values at Each Time Point
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 9 6 2
Mean (Standard Deviation)
Unit of Measure: ug/mL
Month 1 Number Analyzed 9 participants 6 participants 2 participants
-11.231  (24.960) 20.488  (31.024) -27.505  (90.092)
Month 2 Number Analyzed 9 participants 5 participants 2 participants
-15.914  (32.737) 17.716  (33.125) 16.310  (36.077)
Month 3 Number Analyzed 8 participants 5 participants 2 participants
-24.404  (50.084) -2.898  (49.747) 22.355  (19.764)
Month 6 Number Analyzed 6 participants 5 participants 1 participants
-6.823  (44.787) 9.572  (24.927) 91.640 [1]   (NA)
Month 9 Number Analyzed 8 participants 3 participants 1 participants
-0.019  (53.475) 1.177  (27.654) 89.670 [1]   (NA)
Month 12 Number Analyzed 7 participants 3 participants 2 participants
-40.591  (34.977) -23.487  (30.911) -24.905  (17.685)
Final Study Visit (Month 49) Number Analyzed 3 participants 3 participants 0 participants
-28.663  (46.526) -19.770  (74.604)
[1]
SD could not be calculated for a single participant.
Time Frame From Day 1 until the Final Study Visit (up to Month 49)
Adverse Event Reporting Description TEAEs were reported for Safety population. Deaths and TEAEs were monitored together for each cohort regardless of dose administered.
 
Arm/Group Title Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)      0/6 (0.00%)      0/3 (0.00%)    
Hide Serious Adverse Events
Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/10 (10.00%)      3/6 (50.00%)      2/3 (66.67%)    
Blood and lymphatic system disorders       
Anaemia * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 1/3 (33.33%)  1
Gastrointestinal disorders       
Nausea * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Tongue haematoma * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Infections and infestations       
Enterocolitis infectious * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Pneumonia pneumococcal * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Musculoskeletal and connective tissue disorders       
Osteoarthritis * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Rotator cuff syndrome * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Nervous system disorders       
Encephalopathy * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Headache * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Psychiatric disorders       
Suicide attempt * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Vascular disorders       
Deep vein thrombosis * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
1
Term from vocabulary, MedDRA Version 23.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/10 (90.00%)      6/6 (100.00%)      2/3 (66.67%)    
Blood and lymphatic system disorders       
Anaemia * 1  2/10 (20.00%)  4 0/6 (0.00%)  0 0/3 (0.00%)  0
Haemolysis * 1  1/10 (10.00%)  1 1/6 (16.67%)  1 0/3 (0.00%)  0
Aplastic anaemia * 1  0/10 (0.00%)  0 1/6 (16.67%)  2 0/3 (0.00%)  0
Pancytopenia * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Cardiac disorders       
Bradycardia * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Ear and labyrinth disorders       
Tinnitus * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Eye disorders       
Lacrimation increased * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Gastrointestinal disorders       
Diarrhoea * 1  5/10 (50.00%)  8 1/6 (16.67%)  1 0/3 (0.00%)  0
Nausea * 1  4/10 (40.00%)  5 0/6 (0.00%)  0 0/3 (0.00%)  0
Abdominal pain * 1  3/10 (30.00%)  7 0/6 (0.00%)  0 0/3 (0.00%)  0
Constipation * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 1/3 (33.33%)  1
Abdominal distension * 1  1/10 (10.00%)  2 0/6 (0.00%)  0 0/3 (0.00%)  0
Abdominal discomfort * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Abdominal pain upper * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Gastrooesophageal reflux disease * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Large intestine polyp * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Oral discomfort * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Oral pain * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Rectal haemorrhage * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Rectal polyp * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Retching * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Vomiting * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
General disorders       
Fatigue * 1  4/10 (40.00%)  9 2/6 (33.33%)  3 1/3 (33.33%)  1
Injection site bruising * 1  2/10 (20.00%)  2 1/6 (16.67%)  1 0/3 (0.00%)  0
Pyrexia * 1  3/10 (30.00%)  3 0/6 (0.00%)  0 0/3 (0.00%)  0
Chest discomfort * 1  2/10 (20.00%)  2 0/6 (0.00%)  0 0/3 (0.00%)  0
Chest pain * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Chills * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Influenza like illness * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Injection site haematoma * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Hepatobiliary disorders       
Cholelithiasis * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Immune system disorders       
Seasonal allergy * 1  2/10 (20.00%)  3 0/6 (0.00%)  0 0/3 (0.00%)  0
Alloimmunisation * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Drug hypersensitivity * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Infections and infestations       
Nasopharyngitis * 1  4/10 (40.00%)  10 1/6 (16.67%)  2 0/3 (0.00%)  0
Upper respiratory tract infection * 1  4/10 (40.00%)  5 1/6 (16.67%)  1 0/3 (0.00%)  0
Pharyngitis * 1  1/10 (10.00%)  1 1/6 (16.67%)  1 0/3 (0.00%)  0
Sinusitis * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 1/3 (33.33%)  1
Viral infection * 1  1/10 (10.00%)  1 1/6 (16.67%)  1 0/3 (0.00%)  0
Bronchitis * 1  1/10 (10.00%)  2 0/6 (0.00%)  0 0/3 (0.00%)  0
Influenza * 1  1/10 (10.00%)  2 0/6 (0.00%)  0 0/3 (0.00%)  0
Rhinitis * 1  1/10 (10.00%)  2 0/6 (0.00%)  0 0/3 (0.00%)  0
Cystitis * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Ear infection * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Gastroenteritis * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Gastrointestinal infection * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Hordeolum * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Infection * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Oral candidiasis * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Oral herpes * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Respiratory tract infection * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Skin bacterial infection * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Skin infection * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Tooth abscess * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Urinary tract infection * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Injury, poisoning and procedural complications       
Contusion * 1  2/10 (20.00%)  3 0/6 (0.00%)  0 0/3 (0.00%)  0
Post vaccination syndrome * 1  1/10 (10.00%)  2 0/6 (0.00%)  0 0/3 (0.00%)  0
Animal bite * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Bone contusion * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Eye contusion * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Fall * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Foot fracture * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Limb injury * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Post-traumatic pain * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Tooth fracture * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Traumatic haematoma * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Investigations       
Alanine aminotransferase increased * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Aspartate aminotransferase increased * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Grip strength decreased * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
International normalised ratio increased * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Weight decreased * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Metabolism and nutrition disorders       
Hyperkalaemia * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Hypokalaemia * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Vitamin D deficiency * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Back pain * 1  3/10 (30.00%)  9 0/6 (0.00%)  0 1/3 (33.33%)  1
Muscle spasms * 1  2/10 (20.00%)  6 0/6 (0.00%)  0 0/3 (0.00%)  0
Arthralgia * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 1/3 (33.33%)  1
Myalgia * 1  1/10 (10.00%)  1 1/6 (16.67%)  1 0/3 (0.00%)  0
Pain in extremity * 1  1/10 (10.00%)  2 0/6 (0.00%)  0 0/3 (0.00%)  0
Arthritis * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Joint swelling * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Limb discomfort * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Muscle tightness * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Musculoskeletal pain * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Plantar fasciitis * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Rotator cuff syndrome * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma * 1  2/10 (20.00%)  3 0/6 (0.00%)  0 0/3 (0.00%)  0
Nervous system disorders       
Headache * 1  2/10 (20.00%)  4 2/6 (33.33%)  6 1/3 (33.33%)  2
Dizziness * 1  2/10 (20.00%)  4 0/6 (0.00%)  0 0/3 (0.00%)  0
Amnesia * 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Sensory disturbance * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Psychiatric disorders       
Depression * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 1/3 (33.33%)  2
Insomnia * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Renal and urinary disorders       
Paroxysmal nocturnal haemoglobinuria * 1  1/10 (10.00%)  3 0/6 (0.00%)  0 0/3 (0.00%)  0
Chromaturia * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain * 1  3/10 (30.00%)  4 0/6 (0.00%)  0 0/3 (0.00%)  0
Cough * 1  2/10 (20.00%)  2 0/6 (0.00%)  0 1/3 (33.33%)  1
Dyspnoea * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Laryngospasm * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Pleural effusion * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Skin and subcutaneous tissue disorders       
Pruritus * 1  1/10 (10.00%)  2 0/6 (0.00%)  0 0/3 (0.00%)  0
Actinic keratosis * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Psoriasis * 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Rash * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Rash pruritic * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Urticaria * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Vascular disorders       
Hypertension * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Lymphoedema * 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
1
Term from vocabulary, MedDRA Version 23.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: UCB
Organization: Cares
Phone: 001 844 599 2273
EMail: UCBCares@ucb.com
Layout table for additonal information
Responsible Party: UCB Pharma ( Ra Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT03225287    
Other Study ID Numbers: RA101495-01.202
2016-003523-34 ( EudraCT Number )
First Submitted: July 17, 2017
First Posted: July 21, 2017
Results First Submitted: September 7, 2022
Results First Posted: October 27, 2022
Last Update Posted: October 27, 2022