ATLANTA, GA—Findings from a Phase 2 study presented at the 2017 AAAAI Annual Meeting demonstrated that prophylactic administration of recombinant human C1 esterase inhibitor (rhC1INH) once or twice weekly was not only safe but also effective in reducing hereditary angioedema (HAE) attacks.
In this Phase 2, double-blind, multicenter, cross-over study, William Yang, MD, of Ottawa Allergy Research Corporation, in Ottawa, Canada and colleagues aimed to determine the safety and efficacy of prophylactic rhC1INH therapy in the prevention of HAE attacks. Patients included in study were ≥13 years old, had a <50% of normal functional C1INH level, a history of at least 4 monthly HAE attacks for at least 3 months, and no allergies to rabbits.
“Eligible patients were randomized to receive either intravenous rhC1INH (50 IU/kg for patients <84kg; 4200 IU for patients ≥84kg) twice weekly, rhC1INH once weekly in combination with once-weekly saline, or saline twice weekly as part of 1 of 6 treatment sequences,” explained Dr. Yang. For each “treatment sequence”, three individual 4-week periods were followed by a one-week washout period.
The primary endpoint of the study was defined as the number of acute HAE attacks that occurred during a treatment period. One secondary endpoint was evaluated, which was defined by Dr. Yang as “the percentage of patients who achieved a clinical response (≥50% reduction in the number of attacks that occurred during rhC1INH treatment vs. the number of attacks that occurred during saline treatment).”
A total of 32 patients were included in the intention-to-treat population. Dr. Yang reported that the “mean number of HAE attacks was significantly reduced compared with placebo with twice-weekly and once-weekly rhC1INH”. The authors found that the mean number of acute HAE attacks during a treatment sequence was 2.7 for twice-weekly dosing compared to 7.2 for placebo (P<0.0001). For patients in the once-weekly dosing group, the mean number of acute attacks was found to be 4.4 (P=0.0004). The study authors also reported that 74.2% of patients receiving rhC1INH twice-weekly attained clinical response compared to 41.9% of patients receiving rhC1INH once-weekly.
The authors also reported that patients receiving rhC1NH once- and twice-weekly experienced fewer days with HAE symptoms. Patients receiving rhC1INH experience 5.1 days with HAE symptoms versus 8.0 and 10.2 days for once-daily dosing and placebo, respectively.
Safety of rh1CINH therapy was also demonstrated in this study. “Most patients did not experience an adverse event (AE) with rhC1INH administration (65.5% with twice-weekly and 55.2% with once-daily dosing),” the authors explained. Additionally, it was noted that the most commonly reported AEs were headache and nasopharyngitis, which typically occurred ≥24 hours after dosing.
Although safety and efficacy of once- or twice-weekly dosing of rhC1INH was demonstrated in this trial, Dr. Yang did caution, however, that “additional research on weekly rhC1INH for the prevention of HAE attacks is warranted.”