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

Study Overview
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Brief Summary
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The purpose of this study is to enable continued access to zilucoplan (RA101495) for patients with paroxysmal nocturnal hemoglobinuria (PNH) after they complete a zilucoplan clinical study.

Official Title
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A Multicenter, Open-label, Uncontrolled, Extension Study of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria Who Have Completed a RA101495 Clinical Study

Conditions
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Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention / Treatment
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* Drug: Zilucoplan (RA101495)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completion of a qualifying Ra Pharmaceuticals sponsored zilucoplan (RA101495) PNH study Evidence of ongoing clinical benefit in the opinion of the Investigator Exclusion criteria: History of meningococcal disease Current systemic infection or suspicion of active bacterial infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zilucoplan (RA101495)<br>Subjects will continue to receive the final maintenance dose they were receiving in the qualifying study | Drug: Zilucoplan (RA101495)<br>* Subjects will continue to receive the final maintenance dose they were receiving in the qualifying study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs were defined as an AE that occurs after a participant's initial treatment zilucoplan start for this study (RA101495-01.202) that was not present at the time of treatment start, or an AE that increases in severity after treatment start in this study, if the event was present at the time of treatment start. | From Day 1 until the Final Study Visit (up to Month 49) | 
| Percentage of Participants With Serious TEAEs | Serious Adverse event (SAE) was defined as any untoward medical occurrence that:• results in death, • is life-threatening threatening (note that this refers to an event in which the participant was at risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death if it were more severe), • requires hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, and • results in a congenital anomaly/birth defect. | From Day 1 until the Final Study Visit (up to Month 49) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Anti-drug Antibodies (ADA) | Blood samples collection were planned to analyze for the presence/absence of ADAs to zilucoplan for immunogenicity assessments. | At Day 1, Month 1, 2, 3, 6, 9, and 12 | 
| Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point | Serum LDH levels were measure of intravascular hemolysis. As high level of LDH in the blood was indicative of hemolysis in participants with PNH. | 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) | 
| Change From Baseline in Total Bilirubin Values at Each Time Point | Total Bilirubin was monitored for signs and symptoms of hepatic or biliary dysfunction. | 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) | 
| Change From Baseline in Total Hemoglobin Values at Each Time Point | Total Hemoglobin Values were analyzed for hematology assessments. | 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) | 
| Change From Baseline in Free Hemoglobin Values at Each Time Point | Free Hemoglobin Values were analyzed for hematology assessments. | 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) | 
| Change From Baseline in Haptoglobin Values at Each Time Point | Haptoglobin values were analyzed for hematology assessments. | 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) | 
| Change From Baseline in Reticulocytes at Each Time Point | Reticulocytes values were analyzed for hematology assessments. | 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) | 
| Change From Baseline in Hemoglobinuria Values at Each Time Point | Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10 where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria. | 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) | 
| Plasma Concentrations of RA101495 and Its Major Metabolite(s) | Blood samples of RA101495 (zilucoplan) and its metabolites (RA102758 and RA103488) were collected for Plasma concentration analysis. | Predose: At Day 1 (Screening), Month 1, 2, 3, 6, 9, 12, and Final Study Visit (Month 49) | 
| Maximum Plasma Concentration (Cmax) of RA101495 | Cmax is the maximum plasma concentration. | At Day 1, Month 1, 2, 3, 6, 9, and 12 | 
| Time Corresponding to Cmax (Tmax) of RA101495 | tmax is the time to corresponding Cmax. | At Day 1, Month 1, 2, 3, 6, 9, and 12 | 
| Area Under the Drug Concentration-time Curve (AUC0-t) of RA101495 | AUC0-t is area under the drug concentration-time curves. | At Day 1, Month 1, 2, 3, 6, 9, and 12 | 
| Total Complement (CH50) Levels | Blood samples collection were planned to assess complement (CH50) levels. The planned analysis of CH50 was not performed because the CH50 assay was not able to be validated due to lack of reproducibility of the manufacturer's kits. | At Day 1, Month 1, 2, 3, 6, 9, and 12 | 
| Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point | Blood samples were collected for measurement of sRBC lysis for the Classical Complement Pathways. | Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49) | 
| Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point | Blood samples were collected for measurement of membrane attack complex (MAC) by Wieslab ELISA for alternative complement pathway. | Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49) | 
| Change From Baseline in Complement Component 5 (C5) Values at Each Time Point | Blood samples were collected for measurement of Complement component 5 (C5) levels. | Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49) |