Table 1.

Study Design Elements in Randomized Controlled Trials of Long-Term Prophylaxis with C1-INH Replacement Therapies in Adult Patients with HAE

Parameter	Plasma-Derived C1-INH IV22	Plasma-Derived C1-INH SC18	Recombinant Human C1-INH IV21
Study design	Randomized, double-blind, placebo-controlled crossover (phase 3) 2 parallel groups treated in 2 consecutive 12-week periods	Randomized, double-blind, placebo-controlled crossover (phase 3) 2 parallel dose groups treated in 2 consecutive 16-week periods	Randomized, double-blind, placebo-controlled crossover (phase 2) 3 parallel groups sequenced through 3 treatments during 3 consecutive 4-week treatment periods (6 sequences)
Randomization	1:1	1:1:1:1	1:1:1:1:1:1
Treatment	2 Periods pdC1-INH 1000 U or placebo IV q 3–4 days for 12 weeks	2 Periods (2-week washout period between treatments) pdC1-INH (40 IU/kg or 60 IU/kg) or placebo twice weekly for 16 weeks	3 Periods (1-week washout period between treatments) rhC1-INH 50 IU/kg (<84 kg; 4200 U ≥84 kg) twice weekly for 4 weeks or rhC1-INH 50 IU/kg (<84 kg body weight; 4200 U ≥84 kg) once weekly plus placebo once weekly for 4 weeks or Placebo twice weekly for 4 weeks
Eligibility criteria	Age: ≥6 years (n = 22) HAE with low C4 level, normal C1q level, and low antigenic or functional C1-INH level or mutation in C1-INH gene known to cause HAE HAE attacks: history of ≥2 attacks/montha	Age: ≥12 years (n = 90) HAE type 1 or type 2 with functional C1-INH activity <50% and C4 antigen level below normal level HAE attacks for entry into run-in period: ≥4 attacks during a 2-month consecutive period, within 3 months of screeningb HAE attacks during 8-week run-in period: ≥2 attacks within any consecutive 4 weeks or ≥1 attack during first 2 weeks	Age: ≥13 years (n = 32) Functional C1-INH level <50% of normal and history of frequent HAE attacks HAE attacks: ≥4 attacks/month for ≥3 consecutive months before study entryc
Baseline attack frequency	Not specified	Attacks during 3 months before screening, mean (SD) 40 IU dose group (n = 45): 10.8 (6.7) 60 IU dose group (n = 45): 8.8 (6.4)	Attacks during 3 months before study (n = 32) Mean (SD): 17.9 (7.2) Median (range): 14.5 (12–33)

Notes: ^aHAE prophylaxis with stable dosing of androgens or antifibrinolytics permitted. ^bHAE prophylaxis with stable dosing of oral medications (eg, androgens, tranexamic acid, progestins) permitted if received stable dose for 3 months before screening, planned to continue throughout trial, and attack frequency met. Patients who received C1-INH for routine prophylaxis within 3 months before screening and those with significant history of poor response to C1-INH therapy were excluded. ^cHAE prophylaxis with stable dosing of androgens or antifibrinolytics permitted if attack frequency met.

Abbreviations: C1-INH, C1 esterase inhibitor; HAE, hereditary angioedema; IV, intravenous; pdC1-INH, plasma-derived C1-INH; rhC1-INH, recombinant human C1-INH; SC, subcutaneous.