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

• ClinicalTrials.gov Identifier: NCT03225287
• Recruitment Status: Terminated
• First Posted: July 21, 2017
• Results First Posted: October 27, 2022
• Last Update Posted: October 27, 2022
• Sponsor: Ra Pharmaceuticals, Inc.
• 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

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.

Arm/Group Title	Zilucoplan-Cohort A (Eculizumab Naïve)	Zilucoplan-Cohort B (Eculizumab Switch)	Zilucoplan (Inadequate Responder to Eculizumab)
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

Baseline Characteristics

Arm/Group Title		Zilucoplan-Cohort A (Eculizumab Naïve)	Zilucoplan-Cohort B (Eculizumab Switch)	Zilucoplan (Inadequate Responder to Eculizumab)	Total
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
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%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
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)

Outcome Measure Data

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)
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
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)

Outcome Measure Data

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)
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)
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

Outcome Measure Data

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)
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
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)

Outcome Measure Data

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)
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
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)

Outcome Measure Data

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)
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
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)

Outcome Measure Data

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)
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
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)

Outcome Measure Data

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)
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
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)

Outcome Measure Data

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)
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
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)

Outcome Measure Data

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)
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
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)

Outcome Measure Data

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)
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)
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)

Outcome Measure Data

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)
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
Description	Cmax is the maximum plasma concentration.
Time Frame	At Day 1, Month 1, 2, 3, 6, 9, and 12

Outcome Measure Data

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)
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
Description	tmax is the time to corresponding Cmax.
Time Frame	At Day 1, Month 1, 2, 3, 6, 9, and 12

Outcome Measure Data

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)
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
Description	AUC0-t is area under the drug concentration-time curves.
Time Frame	At Day 1, Month 1, 2, 3, 6, 9, and 12

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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
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)

Outcome Measure Data

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)
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
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)

Outcome Measure Data

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)
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
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)

Outcome Measure Data

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)
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.

Adverse Events

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)
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%)
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: UCB
• Organization: Cares
• Phone: 001 844 599 2273
• EMail: UCBCares@ucb.com

• 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