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

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

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.

Study Overview

• Status: Terminated
• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Intervention / Treatment: Drug: Zilucoplan (RA101495)

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Gosford, Australia
    • Investigative Site 3
  • Melbourne, Australia
    • Investigative Site 5
• Canada
  • Toronto, Canada
    • Investigative Site 10
• Finland
  • Helsinki, Finland
    • Investigative Site 14
• Germany
  • Ulm, Germany
    • Investigative Site 9
• Hungary
  • Budapest, Hungary
    • Investigative Site 17
• New Zealand
  • Christchurch, New Zealand
    • Investigative Site 13
  • Hamilton, New Zealand
    • Investigative Site 12
• United Kingdom
  • Leeds, United Kingdom
    • Investigative Site 6
  • London, United Kingdom
    • Investigative Site 7
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Investigative Site 4
  • Texas
    • Dallas, Texas, United States, 75390
      • Investigative Site 19

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Ra Pharmaceuticals, Inc.
• Investigators: Study Chair: Dr. Anita Hill, St James' Institute of Oncology

Publications and helpful links

General Publications

• 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 H. Phase II trials of zilucoplan in paroxysmal nocturnal hemoglobinuria. Haematologica. 2023 Aug 3. doi: 10.3324/haematol.2022.281780. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2017
• Primary Completion (Actual): September 7, 2021
• Study Completion (Actual): October 26, 2021

Study Registration Dates

• First Submitted: July 17, 2017
• First Submitted That Met QC Criteria: July 20, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: RA101495-01.202; 2016-003523-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• IPD Sharing Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No