Plasma-derived C1 esterase inhibitor pharmacokinetics and safety in patients with hereditary angioedema

Over 40 years of use demonstrates that complement 1 esterase inhibitor (C1-INH) concentrate is effective and well tolerated for acute edema attacks and prophylaxis in patients with hereditary angioedema. OCTA-C1-INH is a new stable, virus-inactivated, nanofiltrated concentrate of C1-INH derived from human plasma.

We investigated the pharmacokinetics and safety profile of new C1-INH in people with hereditary angioedema during an attack-free period.

In this prospective, multicenter, open-label, single-arm study, adults with hereditary angioedema type I/II received a single intravenous dose of 20 IU/kg C1-INH. Blood samples were taken ≤30 minutes before infusion, and 0, 0.25, 1, 2, 6, 12, 24, 48, 72, 120, 144, and 168 hours after infusion. The primary end point was assessing the pharmacokinetic parameters of C1-INH measured by C1-INH activity. Safety end points were also examined.

Twenty patients received a single dose of 20 IU/kg new C1-INH with a mean (standard deviation) total dose of 1457.3 (356.51) IU. Mean (standard deviation) area under the curve normalized by dose was 51.6 (17.9) h∙IU/mL/IU, maximum blood concentration was 1.14 (0.989) IU/mL, incremental recovery was 0.0466 (0.051) (IU∙kg)/(IU∙mL), half-life was 0.598 (0.716) hours, and time to maximum concentration was 0.598 (0.716) hours. No thromboembolic events were recorded. No treatment-emergent adverse events were rated as severe/serious.

PK parameters of new C1-INH were in line with those reported for other C1-INH concentrates. New C1-INH demonstrated a favorable safety profile in patients with C1-INH deficiency. Further studies are warranted to determine the effectiveness and longer-term safety of new C1-INH.