MDS-138: Management of Acute Hemolytic Events in Paroxysmal Nocturnal Hemoglobinuria Patients Taking Pegcetacoplan

Context: Acute hemolytic events occurred in completed paroxysmal nocturnal hemoglobinuria (PNH) studies during the pegcetacoplan clinical development program. As part of the long-term extension study, we aim to better understand how to manage acute hemolytic events through dose adjustments in patients treated with the C3 inhibitor pegcetacoplan, recently approved by the FDA. Objective: Establish the long-term safety and efficacy of pegcetacoplan dose adjustments in patients with PNH. Design: This is a multicenter, open-label, nonrandomized extension study (NCT03531255) in PNH patients treated with pegcetacoplan who have previously completed a pegcetacoplan study. Study participants who experience an acute hemolytic event will be offered the opportunity to receive either intensive subcutaneous (SC) or intravenous (IV) pegcetacoplan as an acute treatment. Patients must have lactate dehydrogenase (LDH) >2 times the upper limit of normal and the presence of at least one new or worsening sign or symptom of hemolysis (e.g., decrease in hemoglobin, hemoglobinuria, fatigue), warranting acute intervention in the opinion of the investigator. Interventions: In patients with a steady-state pegcetacoplan dose of 1080 mg SC twice weekly, a loading dose of 1080 mg IV once or 1080 mg SC every 24 hours for 3 doses, followed by an increase in the maintenance dose to 1080 mg SC every 3 days would be used. In patients at steady-state on a pegcetacoplan dose of 1080 mg SC every 3 days, a loading dose of 1080 mg IV once or 1080 mg SC every 24 hours for 3 doses, followed by an increase in the maintenance dose to 1080 mg SC 3 times weekly would be used. Main Outcome Measures: Main outcome measures include incidence and severity of treatment-emergent adverse events, thromboembolic events, hemoglobin level, LDH level, and red blood cell transfusions. Results: Results will be presented upon study completion, estimated in 2022.