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

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

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).

Key Inclusion Criteria:

1. 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%.
2. Received 1200 mg eculizumab every 12 to 16 days (every 2 weeks) for at least 3 months prior to Screening.
3. LDH ≤ 2 x upper limit of normal (ULN) according to central laboratory, at Screening.
4. 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.
5. Body weight ≥ 40 kilograms.

Key Exclusion Criteria:

1. History of major adverse vascular events within 6 months of Day 1.

2. History of bone marrow transplantation.

3. 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.

4. Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1.

5. 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

6. Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.

7. More than 1 LDH value > 2 × ULN within the 6 months prior to Day 1.

8. Platelet count < 30,000/cubic millimeter (30 × 10^9/Liter [L]) at Screening.

9. Absolute neutrophil count < 500/microliter (0.5 × 10^9/L) at Screening.