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.