Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Subcutaneous (SC) Cinryze® (C1 inhibitor (C1 INH) with Recombinant Human Hyaluronidase (rHuPH20) in Subjects with Hereditary Angioedema (HAE)

RationaleHAE manifests as recurrent painful, disabling, and sometimes fatal swelling attacks. CINRYZE administered by the IV route replaces deficient and/or dysfunctional C1 INH and has proven efficacy and safety for both acute treatment and prevention. In order to provide broader options for patients to control disease, the potential enhancement of CINRYZE SC dispersion and absorption when co-administered with rHuPH20 was assessed in HAE patients.MethodsThis open-label, multiple-dose study was conducted in 12 HAE patients who received twice-weekly 1000 or 2000 U SC doses of CINRYZE co-administered as a single injection with rHuPH20 for 2 weeks. Comparisons were made to data from the same subjects who had prior exposure to CINRYZE without rHuPH20. Safety, tolerability, PK/ PD, and immunogenicity were assessed.ResultsSC CINRYZE co-administered with rHuPH20 was well tolerated, with no AEs leading to discontinuation or SAEs. Mild/moderate injection site reactions were noted in the majority of subjects, with severe erythema reported in 2 subjects. Co-administration with rHuPH20 resulted in increased CINRYZE systemic exposure relative to SC administration of CINRYZE alone. Preliminary mean values attained were: functional C1 INH exposure of 36-61 hr·U/mL; Cmax of 0.43-0.72 U/mL; antigenic C1 INH level of 0.13-0.24 g/L and C4 was 174-210 mg/mL. No subjects had detectable C1 INH antibodies in plasma 30 days after the last dose.ConclusionsCINRYZE co-administered as a single SC injection with rHuPH20 was well tolerated and resulted in physiologically relevant functional C1 INH levels. Evaluation of the efficacy and safety of this innovative combination therapy is planned. RationaleHAE manifests as recurrent painful, disabling, and sometimes fatal swelling attacks. CINRYZE administered by the IV route replaces deficient and/or dysfunctional C1 INH and has proven efficacy and safety for both acute treatment and prevention. In order to provide broader options for patients to control disease, the potential enhancement of CINRYZE SC dispersion and absorption when co-administered with rHuPH20 was assessed in HAE patients. HAE manifests as recurrent painful, disabling, and sometimes fatal swelling attacks. CINRYZE administered by the IV route replaces deficient and/or dysfunctional C1 INH and has proven efficacy and safety for both acute treatment and prevention. In order to provide broader options for patients to control disease, the potential enhancement of CINRYZE SC dispersion and absorption when co-administered with rHuPH20 was assessed in HAE patients. MethodsThis open-label, multiple-dose study was conducted in 12 HAE patients who received twice-weekly 1000 or 2000 U SC doses of CINRYZE co-administered as a single injection with rHuPH20 for 2 weeks. Comparisons were made to data from the same subjects who had prior exposure to CINRYZE without rHuPH20. Safety, tolerability, PK/ PD, and immunogenicity were assessed. This open-label, multiple-dose study was conducted in 12 HAE patients who received twice-weekly 1000 or 2000 U SC doses of CINRYZE co-administered as a single injection with rHuPH20 for 2 weeks. Comparisons were made to data from the same subjects who had prior exposure to CINRYZE without rHuPH20. Safety, tolerability, PK/ PD, and immunogenicity were assessed. ResultsSC CINRYZE co-administered with rHuPH20 was well tolerated, with no AEs leading to discontinuation or SAEs. Mild/moderate injection site reactions were noted in the majority of subjects, with severe erythema reported in 2 subjects. Co-administration with rHuPH20 resulted in increased CINRYZE systemic exposure relative to SC administration of CINRYZE alone. Preliminary mean values attained were: functional C1 INH exposure of 36-61 hr·U/mL; Cmax of 0.43-0.72 U/mL; antigenic C1 INH level of 0.13-0.24 g/L and C4 was 174-210 mg/mL. No subjects had detectable C1 INH antibodies in plasma 30 days after the last dose. SC CINRYZE co-administered with rHuPH20 was well tolerated, with no AEs leading to discontinuation or SAEs. Mild/moderate injection site reactions were noted in the majority of subjects, with severe erythema reported in 2 subjects. Co-administration with rHuPH20 resulted in increased CINRYZE systemic exposure relative to SC administration of CINRYZE alone. Preliminary mean values attained were: functional C1 INH exposure of 36-61 hr·U/mL; Cmax of 0.43-0.72 U/mL; antigenic C1 INH level of 0.13-0.24 g/L and C4 was 174-210 mg/mL. No subjects had detectable C1 INH antibodies in plasma 30 days after the last dose. ConclusionsCINRYZE co-administered as a single SC injection with rHuPH20 was well tolerated and resulted in physiologically relevant functional C1 INH levels. Evaluation of the efficacy and safety of this innovative combination therapy is planned. CINRYZE co-administered as a single SC injection with rHuPH20 was well tolerated and resulted in physiologically relevant functional C1 INH levels. Evaluation of the efficacy and safety of this innovative combination therapy is planned.