GTH 2017, 61st Annual Meeting of the Society of Thrombosis and Hemostasis Research

Randomized, double-blind, placebo-controlled trial of recombinant human C1 inhibitor for prophylaxis of hereditary angioedema attacks

B. Giannetti¹, V. Grivcheva Panovska², D. Moldovan³, A. Reshef⁴, S. Andrejevic⁵, R. Hakl⁶, S. Kivity⁷, L. Bellizzi¹, A. Relan¹, B. Giannetti¹, M. Cicardi⁸ (¹Leiden, The Netherlands, ²Skopje, Republic of Macedonia, ³Tirgu Mures, Romania, ⁴Tel-Hashomer, Israel, ⁵Belgrade, Serbia, ⁶Brno, Czech Republic, ⁷Tel Aviv, Israel, ⁸Milan, Italy)

Vascular Wall, Platelets and Acquired Problems
Date: 16.02.2017,
Time: 14:00 - 15:15

Objective: Recombinant human C1 inhibitor (rhC1INH) is an approved, on-demand treatment for hereditary angioedema (HAE) attacks. Open-label data suggest that rhC1INH may prevent HAE attacks.

Methods: Patients ≥13 years of age with functional C1INH levels <50% of normal and history of ≥4 HAE attacks during the preceding 3 months were included in this phase 2, double-blind, 3-period crossover study. Patients received intravenous rhC1INH 50 IU/kg (max, 4200 IU) once and twice weekly and placebo in three 4-week treatment periods that were separated by 1 week. With the crossover design, all patients received each of the dosing regimens. Attack symptoms were recorded daily. The number of HAE attacks per 4-week treatment phase (primary endpoint) and percentage of patients with clinical response (≥50% reduction in number of attacks from treatment with placebo to treatment with rhC1INH; secondary endpoint) were determined. Adverse events (AEs) and immunogenicity were also assessed.

Results: Thirty-two patients were randomized to treatment. Mean number of HAE attacks was significantly reduced with rhC1INH twice weekly (P < 0.0001) and once weekly (P = 0.0004) versus placebo (Figure). Most patients (74.2%; 95% CI, 57-86) who received rhC1INH twice weekly and 41.9% (95% CI, 26-59) who received rhC1INH once weekly had ≥50% reduction in number of HAE attacks. No patients withdrew because of AEs and no thrombotic or thromboembolic events, drug hypersensitivity or anaphylactic reactions, or neutralizing antibodies were reported.

Conclusion: rhC1INH provided clinically relevant reductions in HAE attack frequency and was well-tolerated. Data support the continued development of rhC1INH for HAE prophylaxis.