Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients Who Have an Inadequate Response to Eculizumab

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety and efficacy of RA101495 in patients with paroxysmal nocturnal hemoglobinuria (PNH) who have an inadequate response to eculizumab. Patients will be treated with RA101495 for 12 weeks.

Official Title
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A Phase 2 Multicenter, Open-Label, Uncontrolled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria Who Have an Inadequate Response to Eculizumab

Conditions
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Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention / Treatment
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* Drug: Zilucoplan (RA101495)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of PNH by flow cytometry Inadequate response to eculizumab defined as having received eculizumab for at least 6 months plus a documented LDH level ≥ 1.5 x the upper limit of normal (ULN) and/or the presence of a known C5 mutation conferring resistance to eculizumab Exclusion Criteria: History of meningococcal disease Current systemic infection or suspicion of active bacterial infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zilucoplan (RA101495)<br>Subjects will receive RA101495 at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC | Drug: Zilucoplan (RA101495)<br>* 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Levels. | Change-from-baseline through Week 12 in serum lactate dehydrogenase (LDH) levels | Through Week 12 of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change-from-baseline Bilirubin Values | Changes from baseline at each of the scheduled postbaseline time-points | Through week 12 | 
| Change-from-baseline Total Hemoglobin Values | Changes from baseline at each of the scheduled postbaseline time-points | Through week 12 | 
| Change-from-baseline Free Hemoglobin Values | Changes from baseline at each of the scheduled postbaseline time-points | Through week 12 | 
| Change-from-baseline Haptoglobin Values | Changes from baseline at each of the scheduled postbaseline time-points | Through week 12 | 
| Change-from-baseline Reticulocyte Values | Changes from baseline at each of the scheduled postbaseline time-points | Through week 12 | 
| Change-from-baseline Hemoglobinuria Values | Changes from baseline at each of the scheduled postbaseline 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. | Through week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PNH