Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients
Primary Purpose
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Zilucoplan (RA101495)
Sponsored by
About this trial
This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria (PNH) focused on measuring PNH
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of PNH by flow cytometry
- For treatment naive patients: subjects must not have received treatment with eculizumab prior to or during the Screening Period and must have a lactate dehydrogenase (LDH) level ≥2 times the upper limit of normal (xULN) during Screening
- For patients who previously received eculizumab: subjects must have received treatment with eculizumab for at least 6 months prior to Screening
Exclusion Criteria:
- History of meningococcal disease
- Current systemic infection or suspicion of active bacterial infection
Sites / Locations
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
- Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Zilucoplan (RA101495) treatment naive
Zilucoplan (RA101495) previously on eculizumab
Arm Description
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC (treatment naïve)
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC (previously on eculizumab)
Outcomes
Primary Outcome Measures
Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Level.
The primary efficacy endpoint is the change-from-baseline in serum LDH levels during this period, defined as the mean LDH values of Weeks 6, 8, 10, and 12 minus the baseline value of LDH.
Secondary Outcome Measures
Changes From Baseline in Bilirubin Values
Changes from baseline at each of the scheduled post-baseline time-points
Total Hemoglobin
Changes from baseline at each of the scheduled post-baseline time-points
Changes From Baseline in Free Hemoglobin Values
Changes from baseline at each of the scheduled post-baseline time-points
Haptoglobin Values
Changes from baseline at each of the scheduled post-baseline time-points
Reticulocyte Values
Changes from baseline at each of the scheduled post-baseline time-points
Hemoglobinuria Values
Changes from baseline at each of the scheduled post-baseline time-points; 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03078582
Brief Title
Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients
Official Title
Phase 2 Multicenter, Open-Label, Uncontrolled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
March 8, 2017 (Actual)
Primary Completion Date
March 28, 2018 (Actual)
Study Completion Date
March 28, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ra Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of the study is to evaluate the safety and efficacy of zilucoplan (RA101495) in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). There will be two groups of patients in the study: the first group will include patients who have never received eculizumab for treatment of PNH. The second group will include patients who have received treatment with eculizumab for at least 6 months prior to the study. Patients will be treated with RA101495 for 12 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords
PNH
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Zilucoplan (RA101495) treatment naive
Arm Type
Experimental
Arm Description
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC (treatment naïve)
Arm Title
Zilucoplan (RA101495) previously on eculizumab
Arm Type
Experimental
Arm Description
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC (previously on eculizumab)
Intervention Type
Drug
Intervention Name(s)
Zilucoplan (RA101495)
Intervention Description
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
Primary Outcome Measure Information:
Title
Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Level.
Description
The primary efficacy endpoint is the change-from-baseline in serum LDH levels during this period, defined as the mean LDH values of Weeks 6, 8, 10, and 12 minus the baseline value of LDH.
Time Frame
Through Week 12 of the study
Secondary Outcome Measure Information:
Title
Changes From Baseline in Bilirubin Values
Description
Changes from baseline at each of the scheduled post-baseline time-points
Time Frame
Through Week 12 of the study
Title
Total Hemoglobin
Description
Changes from baseline at each of the scheduled post-baseline time-points
Time Frame
Through Week 12 of the Study
Title
Changes From Baseline in Free Hemoglobin Values
Description
Changes from baseline at each of the scheduled post-baseline time-points
Time Frame
Through Week 12 of the study
Title
Haptoglobin Values
Description
Changes from baseline at each of the scheduled post-baseline time-points
Time Frame
Through Week 12 of the Study
Title
Reticulocyte Values
Description
Changes from baseline at each of the scheduled post-baseline time-points
Time Frame
Through Week 12 of the Study
Title
Hemoglobinuria Values
Description
Changes from baseline at each of the scheduled post-baseline time-points; 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.
Time Frame
Through Week 12 of the Study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of PNH by flow cytometry
For treatment naive patients: subjects must not have received treatment with eculizumab prior to or during the Screening Period and must have a lactate dehydrogenase (LDH) level ≥2 times the upper limit of normal (xULN) during Screening
For patients who previously received eculizumab: subjects must have received treatment with eculizumab for at least 6 months prior to Screening
Exclusion Criteria:
History of meningococcal disease
Current systemic infection or suspicion of active bacterial infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. Anita Hill
Organizational Affiliation
St James' Institute of Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Investigative Site
City
Gosford
State/Province
New South Wales
Country
Australia
Facility Name
Investigative Site
City
Parkville
Country
Australia
Facility Name
Investigative Site
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Investigative Site
City
Copenhagen
Country
Denmark
Facility Name
Investigative Site
City
Helsinki
Country
Finland
Facility Name
Investigative Site
City
Essen
Country
Germany
Facility Name
Investigative Site
City
Ulm
Country
Germany
Facility Name
Investigative Site
City
Budapest
Country
Hungary
Facility Name
Investigative Site
City
Christchurch
Country
New Zealand
Facility Name
Investigative Site
City
Hamilton
Country
New Zealand
Facility Name
Investigative Site
City
Leeds
Country
United Kingdom
Facility Name
Investigative Site
City
London
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://learningcenter.ehaweb.org/eha/2018/stockholm/214782/anita.hill.ra101495.a.subcutaneously-administered.peptide.inhibitor.of.html?f=menu=14*media=3*speaker=664274
Description
Related Info
Learn more about this trial
Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients
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