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 Description

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.

Condition or disease	Intervention/treatment	Phase
Paroxysmal Nocturnal Hemoglobinuria (PNH)	Drug: Zilucoplan (RA101495)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label, Uncontrolled, Extension Study of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria Who Have Completed a RA101495 Clinical Study
• Actual Study Start Date: July 17, 2017
• Actual Primary Completion Date: September 7, 2021
• Actual Study Completion Date: October 26, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 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.
2. Percentage of Participants With Serious TEAEs [ Time Frame: 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 :

1. Number of Participants With Anti-drug Antibodies (ADA) [ Time Frame: 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.
2. Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point [ 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) ]
   Serum LDH levels were measure of intravascular hemolysis. As high level of LDH in the blood was indicative of hemolysis in participants with PNH.
3. Change From Baseline in Total Bilirubin Values at Each Time Point [ 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) ]
   Total Bilirubin was monitored for signs and symptoms of hepatic or biliary dysfunction.
4. Change From Baseline in Total Hemoglobin Values at Each Time Point [ 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) ]
   Total Hemoglobin Values were analyzed for hematology assessments.
5. Change From Baseline in Free Hemoglobin Values at Each Time Point [ 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) ]
   Free Hemoglobin Values were analyzed for hematology assessments.
6. Change From Baseline in Haptoglobin Values at Each Time Point [ 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) ]
   Haptoglobin values were analyzed for hematology assessments.
7. Change From Baseline in Reticulocytes at Each Time Point [ 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) ]
   Reticulocytes values were analyzed for hematology assessments.
8. Change From Baseline in Hemoglobinuria Values at Each Time Point [ 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) ]
   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.
9. Plasma Concentrations of RA101495 and Its Major Metabolite(s) [ Time Frame: 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.
10. Maximum Plasma Concentration (Cmax) of RA101495 [ Time Frame: At Day 1, Month 1, 2, 3, 6, 9, and 12 ]
    Cmax is the maximum plasma concentration.
11. Time Corresponding to Cmax (Tmax) of RA101495 [ Time Frame: At Day 1, Month 1, 2, 3, 6, 9, and 12 ]
    tmax is the time to corresponding Cmax.
12. Area Under the Drug Concentration-time Curve (AUC0-t) of RA101495 [ Time Frame: At Day 1, Month 1, 2, 3, 6, 9, and 12 ]
    AUC0-t is area under the drug concentration-time curves.
13. Total Complement (CH50) Levels [ Time Frame: 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.
14. Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point [ Time Frame: 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.
15. Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point [ Time Frame: 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.
16. Change From Baseline in Complement Component 5 (C5) Values at Each Time Point [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Investigative Site 4

Los Angeles, California, United States, 90033

United States, Texas

Investigative Site 19

Dallas, Texas, United States, 75390

Australia

Investigative Site 3

Gosford, Australia

Investigative Site 5

Melbourne, Australia

Canada

Investigative Site 10

Toronto, Canada

Finland

Investigative Site 14

Helsinki, Finland

Germany

Investigative Site 9

Ulm, Germany

Hungary

Investigative Site 17

Budapest, Hungary

New Zealand

Investigative Site 13

Christchurch, New Zealand

Investigative Site 12

Hamilton, New Zealand

United Kingdom

Investigative Site 6

Leeds, United Kingdom

Investigative Site 7

London, United Kingdom

Sponsors and Collaborators

Ra Pharmaceuticals, Inc.

Investigators

• Study Chair: Dr. Anita Hill; St James' Institute of Oncology

  Study Documents (Full-Text)

Documents provided by UCB Pharma ( Ra Pharmaceuticals, Inc. ):

Study Protocol  [PDF] October 20, 2016

Statistical Analysis Plan  [PDF] October 15, 2021

More Information

• Responsible Party: Ra Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03225287
• Other Study ID Numbers: RA101495-01.202; 2016-003523-34 ( EudraCT Number )
• First Posted: July 21, 2017
• Results First Posted: October 27, 2022
• Last Update Posted: October 27, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• 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.
• 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.
• URL: http://www.Vivli.org

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hemoglobinuria; Hemoglobinuria, Paroxysmal; Proteinuria; Urination Disorders; Urologic Diseases; Urological Manifestations; Anemia, Hemolytic; Anemia; Hematologic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases