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

Paroxysmal Nocturnal Hemoglobinuria (PNH) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03225287
• Other study ID #: RA101495-01.202
• Secondary ID: 2016-003523-34
• Status: Terminated
• Phase: Phase 2
• Start date: July 17, 2017
• Est. completion date: October 26, 2021

Study information

• Verified date: September 2023
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: October 26, 2021
• Est. primary completion date: September 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention

Drug:
• Zilucoplan (RA101495)
Subjects will continue to receive the final maintenance dose they were receiving in the qualifying study.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ra Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Finland,  Germany,  Hungary,  New Zealand,  United Kingdom, 

References & Publications (1)

Kulasekararaj AG, Lehtinen AE, Forsyth C, Gandhi S, Griffin M, Korper S, Mikala G, Muus P, Overgaard U, Patriquin CJ, Pullon H, Shen YM, Spearing R, Szer J, De la Borderie G, Duda PW, Farzaneh-Far R, Ragunathan S, Sayegh CE, Vadysirisack DD, Schrezenmeier — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)	TEAEs were defined as an AE that occurs after a participant's initial treatment zilucoplan start for this study (RA101495-01.202) that was not present at the time of treatment start, or an AE that increases in severity after treatment start in this study, if the event was present at the time of treatment start.	From Day 1 until the Final Study Visit (up to Month 49)
Primary	Percentage of Participants With Serious TEAEs	Serious Adverse event (SAE) was defined as any untoward medical occurrence that:• results in death, • is life-threatening threatening (note that this refers to an event in which the participant was at risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death if it were more severe), • requires hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, and • results in a congenital anomaly/birth defect.	From Day 1 until the Final Study Visit (up to Month 49)
Secondary	Number of Participants With Anti-drug Antibodies (ADA)	Blood samples collection were planned to analyze for the presence/absence of ADAs to zilucoplan for immunogenicity assessments.	At Day 1, Month 1, 2, 3, 6, 9, and 12
Secondary	Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point	Serum LDH levels were measure of intravascular hemolysis. As high level of LDH in the blood was indicative of hemolysis in participants with PNH.	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)
Secondary	Change From Baseline in Total Bilirubin Values at Each Time Point	Total Bilirubin was monitored for signs and symptoms of hepatic or biliary dysfunction.	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Change From Baseline in Hemoglobinuria Values at Each Time Point	Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10 where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria.	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)
Secondary	Plasma Concentrations of RA101495 and Its Major Metabolite(s)	Blood samples of RA101495 (zilucoplan) and its metabolites (RA102758 and RA103488) were collected for Plasma concentration analysis.	Predose: At Day 1 (Screening), Month 1, 2, 3, 6, 9, 12, and Final Study Visit (Month 49)
Secondary	Maximum Plasma Concentration (Cmax) of RA101495	Cmax is the maximum plasma concentration.	At Day 1, Month 1, 2, 3, 6, 9, and 12
Secondary	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
Secondary	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
Secondary	Total Complement (CH50) Levels	Blood samples collection were planned to assess complement (CH50) levels. The planned analysis of CH50 was not performed because the CH50 assay was not able to be validated due to lack of reproducibility of the manufacturer's kits.	At Day 1, Month 1, 2, 3, 6, 9, and 12
Secondary	Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point	Blood samples were collected for measurement of sRBC lysis for the Classical Complement Pathways.	Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)
Secondary	Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point	Blood samples were collected for measurement of membrane attack complex (MAC) by Wieslab ELISA for alternative complement pathway.	Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)
Secondary	Change From Baseline in Complement Component 5 (C5) Values at Each Time Point	Blood samples were collected for measurement of Complement component 5 (C5) levels.	Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)