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

Recruitment & Eligibility

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.

Study & Design

Arm && Interventions

Group	Intervention	Description
Ravulizumab	Eculizumab	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).
Ravulizumab	Ravulizumab	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).

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experienced Free C5-associated BTH	Baseline through Day 351	Free C5-associated BTH was defined as BTH concurrent with free C5 concentrations ≥0.5 micrograms (μg)/milliliter (mL). BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath \[dyspnea\], anemia \[hemoglobin \<10 grams {g}/deciliter {dL}\], major adverse vascular event \[MAVE\], including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated lactate dehydrogenase (LDH) ≥2 \* upper limit of normal (ULN).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experienced BTH	Baseline through Day 351	BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath \[dyspnea\], anemia \[hemoglobin \<10 g/dL\], MAVE, including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 \* ULN.
Percentage of Participants With Stabilized Hemoglobin	Baseline through Day 351	Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion from Baseline to Day 351.
Percent Change From Baseline in LDH at Day 351	Baseline, Day 351
Percentage of Participants Who Received a Red Blood Cell (RBC) Transfusion	Baseline through Day 351

Recruitment & Eligibility