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

Phase 2

Terminated

Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)

Interventions: Drug: Zilucoplan (RA101495)

Registration Number: NCT03225287

Lead Sponsor: Ra Pharmaceuticals, Inc.

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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 19

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Zilucoplan (RA101495)	Zilucoplan (RA101495)	Subjects will continue to receive the final maintenance dose they were receiving in the qualifying study

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Complement Component 5 (C5) Values at Each Time Point	Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)	Blood samples were collected for measurement of Complement component 5 (C5) levels.
Number of Participants With Anti-drug Antibodies (ADA)	At Day 1, Month 1, 2, 3, 6, 9, and 12	Blood samples collection were planned to analyze for the presence/absence of ADAs to zilucoplan for immunogenicity assessments.
Change From Baseline in Total Hemoglobin Values at Each Time Point	Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)	Total Hemoglobin Values were analyzed for hematology assessments.
Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point	Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)	Serum LDH levels were measure of intravascular hemolysis. As high level of LDH in the blood was indicative of hemolysis in participants with PNH.
Change From Baseline in Total Bilirubin Values at Each Time Point	Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)	Total Bilirubin was monitored for signs and symptoms of hepatic or biliary dysfunction.
Change From Baseline in Free Hemoglobin Values at Each Time Point	Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)	Free Hemoglobin Values were analyzed for hematology assessments.
Change From Baseline in Haptoglobin Values at Each Time Point	Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)	Haptoglobin values were analyzed for hematology assessments.
Change From Baseline in Reticulocytes at Each Time Point	Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)	Reticulocytes values were analyzed for hematology assessments.
Change From Baseline in Hemoglobinuria Values at Each Time Point	Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and Final Study Visit (Month 49)	Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10 where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria.
Plasma Concentrations of RA101495 and Its Major Metabolite(s)	Predose: At Day 1 (Screening), Month 1, 2, 3, 6, 9, 12, and Final Study Visit (Month 49)	Blood samples of RA101495 (zilucoplan) and its metabolites (RA102758 and RA103488) were collected for Plasma concentration analysis.
Maximum Plasma Concentration (Cmax) of RA101495	At Day 1, Month 1, 2, 3, 6, 9, and 12	Cmax is the maximum plasma concentration.
Time Corresponding to Cmax (Tmax) of RA101495	At Day 1, Month 1, 2, 3, 6, 9, and 12	tmax is the time to corresponding Cmax.
Area Under the Drug Concentration-time Curve (AUC0-t) of RA101495	At Day 1, Month 1, 2, 3, 6, 9, and 12	AUC0-t is area under the drug concentration-time curves.
Total Complement (CH50) Levels	At Day 1, Month 1, 2, 3, 6, 9, and 12	Blood samples collection were planned to assess complement (CH50) levels. The planned analysis of CH50 was not performed because the CH50 assay was not able to be validated due to lack of reproducibility of the manufacturer's kits.
Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point	Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)	Blood samples were collected for measurement of sRBC lysis for the Classical Complement Pathways.
Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point	Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)	Blood samples were collected for measurement of membrane attack complex (MAC) by Wieslab ELISA for alternative complement pathway.

Trial Locations

Locations (12): Investigative Site 14
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Helsinki, Finland
Investigative Site 4
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Los Angeles, California, United States
Investigative Site 19
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Dallas, Texas, United States
Investigative Site 5
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Melbourne, Australia
Investigative Site 9
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Ulm, Germany
Investigative Site 3
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Gosford, Australia
Investigative Site 10
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Toronto, Canada
Investigative Site 17
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Budapest, Hungary
Investigative Site 13
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Christchurch, New Zealand
Investigative Site 6
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Leeds, United Kingdom
Investigative Site 12
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Hamilton, New Zealand
Investigative Site 7
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London, United Kingdom