Table 1 Features of COMPACT [14] and CHANGE [11, 17] studies

C1-INH formulation

Subcutaneous

Intravenous

Study phase

III

III

Study design

Twice-weekly, dosed by body-weight, C1-INH(SC), 40 or 60 IU/kg for 16 weeks, preceded or followed by placebo for 16 weeks

Twice-weekly, fixed dose, C1-INH(IV) 1000 U for 12 weeks, preceded or followed by placebo for 12 weeks

Inclusion Criteria

Age ≥ 12 years

C1-INH-HAE type I/II confirmed by central laboratory

≥ 4 HAE attacks over consecutive 2 months within 3 months before screening

Stable oral HAE prophylaxis regimen permitted^a

Age ≥ 6 years

C1-INH-HAE confirmed by laboratory analysis

Frequent HAE attacks ≥ 2 per month

Normal C1q level

Exclusion Criteria

History of arterial/venous thrombosis requiring anticoagulant therapy or current prothrombotic risk

History of poor response to C1-INH therapy for the management of HAE

Incurable malignancies

C1-INH(IV) routine HAE prophylaxis within 3 months of screening^a

Pregnant, nursing, or plan to become pregnant during the study

Alcohol, drug, or medication abuse within 1 year of screening

Known or suspected hypersensitivity to the investigational product

Participated in another interventional clinical study within 30 days of screening

Unable to have HAE adequately managed with on-demand treatment

Any clinically significant medical condition, e.g., renal failure, that would interfere with participation

Presence of anti-C1-INH autoantibody

B cell malignancy

Participation in a C1 esterase inhibitor trial, or received blood/blood product in the past 90 days

Pregnancy or lactation

Narcotic addiction

History of allergic reaction to C1-INH or other blood products

Participation in any other investigational drug study within the past 30 days

Low C1q level