Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab

Study Overview
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Brief Summary
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The primary purpose of this study is to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab in participants who are prescribed and are receiving a higher than approved dose of eculizumab to treat paroxysmal nocturnal hemoglobinuria (PNH).

Official Title
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Phase 4, Single-Arm Study of Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab

Conditions
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Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
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* Biological: Eculizumab
* Biological: Ravulizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation of red blood cells and white blood cells, with granulocyte or monocyte clone size of ≥ 5%. Received 1200 mg eculizumab every 12 to 16 days (every 2 weeks) for at least 3 months prior to Screening. LDH ≤ 2 x upper limit of normal (ULN) according to central laboratory, at Screening. To reduce the risk of meningococcal infection (Neisseria meningitidis), all participants must be vaccinated against meningococcal infections within 3 years prior to initiating study drug. Body weight ≥ 40 kilograms. Key Exclusion Criteria: History of major adverse vascular events within 6 months of Day 1. History of bone marrow transplantation. Lymphoma, leukemia, myelodysplastic syndrome, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1. Concomitant use of any of the following medications and not on a stable regimen (as judged by the Investigator) for the time period indicated prior to Screening: Erythropoietin or immunosuppressants for at least 8 weeks Systemic corticosteroids for at least 4 weeks Vitamin K antagonists (for example, warfarin) with a stable international normalized ratio level for at least 4 weeks Iron supplements or folic acid for 4 weeks Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study. More than 1 LDH value > 2 × ULN within the 6 months prior to Day 1. Platelet count < 30,000/cubic millimeter (30 × 10^9/Liter [L]) at Screening. Absolute neutrophil count < 500/microliter (0.5 × 10^9/L) at Screening.

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: Ravulizumab<br>Participants will receive eculizumab during the 3-month Screening Period. Participants will then switch over to and receive weight-based doses of ravulizumab for the duration of the study Treatment Period (351 days). | Biological: Eculizumab<br>* Participants must have been prescribed and be receiving a stable dose of eculizumab 1200 milligrams (mg) every 2 weeks (q2w) for at least 3 months prior to the Screening Period. During the Screening Period, participants will continue to receive eculizumab 1200 mg q2w.<br>* Other names: Soliris;Biological: Ravulizumab<br>* During the Treatment Period, participants will receive a loading dose of ravulizumab on Day 1, followed by maintenance doses on Day 15 and every 8 weeks, administered by intravenous infusion. Ravulizumab loading and maintenance doses will be based on participants' body weight per approved dose regimen.<br>* Other names: Ultomiris;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion Of Participants Who Experience Free Complement Component 5 (C5)-associated Breakthrough Hemolysis (BTH) |  | Baseline through Day 351 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion Of Participants Who Experience BTH |  | Baseline through Day 351 | 
| Hemolysis As Directly Measured By Lactate Dehydrogenase (LDH) Percent Change From Baseline To Day 351 |  | Baseline, Day 351 | 
| Proportion Of Participants Who Receive A Transfusion |  | Baseline through Day 351 | 
| Proportion Of Participants With Stabilized Hemoglobin |  | Baseline through Day 351 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paroxysmal Nocturnal Hemoglobinuria, PNH, Ravulizumab, Ultomiris, Eculizumab, Soliris