Efficacy, Safety and Immunogenicity Study of Recombinant Human C1 Inhibitor for the Treatment of Acute HAE Attacks

A Phase III Randomized, Double-blind, Placebo-controlled Study With an Open-label Extension Evaluating the Efficacy, Safety and Immunogenicity of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks of Angioedema in Patients With HAE

This study is being conducted to confirm the efficacy, safety, and immunogenicity of recombinant human C1 inhibitor (rhC1INH) at a dose of 50 U/kg when used for the treatment of acute angioedema attacks in Hereditary Angioedema (HAE) patients.

HAE is characterized by recurrent localized angioedema caused by uncontrolled activation of the complement and contact systems due to a congenital deficiency of functional C1 inhibitor.

rhC1INH has been developed to offer a more widely available therapeutic alternative to the existing plasma-derived C1INH (pdC1INH) products that have been used in the treatment of acute angioedema attacks patients with HAE.

Patients who have qualified for enrollment in advance and who present to a study center within 5 hours of onset of an attack will be evaluated for eligibility. 75 eligible patients will be randomized (3:2) to receive an intravenous infusion of rhC1INH or saline in a double-blind fashion. Open-label rhC1INH may be provided as rescue medication to patients who do not experience the beginning of relief within 4 hours or who experience life-threatening oropharyngeal-laryngeal angioedema symptoms.

Any patient having received a randomized treatment will be allowed to receive treatment with rhC1INH in an open-label fashion for subsequent eligible attacks.

Inclusion Criteria:

• Aged at least 13 years
• Signed written informed consent
• Clear clinical and laboratory diagnosis of HAE with baseline plasma level of functional C1INH of less than 50% of normal
• Willingness and ability to comply with all protocol procedures
• Clinical symptoms of an eligible HAE attack with onset less than 5 hours before the time of initial evaluation

Exclusion Criteria:

• Medical history of allergy to rabbits or rabbit-derived products (including rhC1INH), or positive anti-rabbit dander IgE test (cut off >0.35 kU/L; ImmunoCap® assay; Phadia or equivalent).
• A diagnosis of acquired C1INH deficiency (AAE)
• Pregnancy, or breastfeeding, or current intention to become pregnant
• Treatment with any investigational drug in the past 30 days
• Known or suspected addiction to drug and/or alcohol abuse
• Suspicion for an alternate explanation of the symptoms other than acute HAE attack