Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients

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 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.

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

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 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

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zilucoplan (RA101495) treatment naive<br>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) | Drug: Zilucoplan (RA101495)<br>* 0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC<br>|
| Experimental: Zilucoplan (RA101495) previously on eculizumab<br>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) | Drug: Zilucoplan (RA101495)<br>* 0.3mg/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) 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. | Through Week 12 of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline in Bilirubin Values | Changes from baseline at each of the scheduled post-baseline time-points | Through Week 12 of the study | 
| Total Hemoglobin | Changes from baseline at each of the scheduled post-baseline time-points | Through Week 12 of the Study | 
| Changes From Baseline in Free Hemoglobin Values | Changes from baseline at each of the scheduled post-baseline time-points | Through Week 12 of the study | 
| Haptoglobin Values | Changes from baseline at each of the scheduled post-baseline time-points | Through Week 12 of the Study | 
| Reticulocyte Values | Changes from baseline at each of the scheduled post-baseline time-points | Through Week 12 of the Study | 
| 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. | Through Week 12 of the Study | 

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