Current options for prophylaxis of acute HAE attacks are very limited. The international, prospective, double-blind, crossover, phase III COMPACT trial evaluated a volume-reduced, subcutaneous C1-inhibitor preparation, CSL830, for the prevention of HAE attacks.

After obtaining written consent, patients with type I/II HAE were randomized to one of four treatment sequences, each involving two 16-week treatment periods: 40 IU/kg twice-weekly followed by placebo, or vice versa; or similarly with 60 IU/kg. The primary efficacy endpoint was the time-normalized number of HAE attacks. Secondary efficacy endpoints were the proportion of responders ( at least 50 % reduction in time-normalized number of HAE attacks versus placebo) and time-normalized number of rescue medication uses. Adverse events (AEs) were monitored throughout.

Of 90 patients randomized, 79 completed the study. Both doses of CSL830 reduced the time-normalized attack rate versus placebo (both p<0.001); mean difference –2.42 attacks/month (95 % CI: –3.38, –1.46), corresponding to an 89 % median reduction (40 IU/kg), and –3.51 attacks/month (95 % CI: –4.21, –2.81) corresponding to a 95 % median reduction (60 IU/kg). Response rates were 76 % (95 % CI: 62, 87) (40 IU/kg) and 90 % (95 % CI: 77, 96) (60 IU/kg). Need for HAE rescue medication was reduced from 5.55 (placebo) to 1.13 uses/month (40 IU/kg) and from 3.89 (placebo) to 0.32 uses/month (60 IU/kg). AEs were reported in a similar proportion of patients across treatments; most were injection-site reactions, which were generally of mild severity and transient.

The self-administered, subcutaneous C1-inhibitor CSL830 was highly efficacious for preventing HAE attacks.
(Source: ACAAI oral abstract O002 presented 13 November 2016)