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

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