KalVista Pharmaceuticals has presented pharmacokinetic, pharmacodynamic, and safety data from a phase 1 study supporting the use of sebetralstat as a short-term prophylaxis treatment in the KONFIDENT-S trial for hereditary angioedema (HAE).
The results of the phase 1 study, which were presented at the 13th C1 Inhibitor Deficiency and Angioedema Workshop, confirmed that 3 doses of sebetralstat within 24 hours were well tolerated and led to drug accumulation.
The administration of 600 mg of sebetralstat resulted in a geometric mean plasma kallikrein inhibition greater than 90% within 30 minutes of dose 1 in all study cohorts. Furthermore, it remained superior to 80% through 28 hours after 3 doses of sebetralstat in the cohort receiving the drug every 8 hours.
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“Based on these data, KONFIDENT-S will prospectively evaluate the effectiveness and safety of three doses of 600 mg of sebetralstat administered before and approximately 6 hours after each previous dose in the periprocedural STP [short-term prophylaxis] setting,” the study’s authors said.
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The phase 1, double-blind, placebo-controlled, multiple-dose, multiple-cohort study evaluated the safety, tolerability, and pharmacokinetics of multiple doses of 600 mg of sebetralstat in healthy adults under fasted conditions.
Participants were randomized to 1 of 3 cohorts, who received 600 mg of sebetralstat or placebo with different dosing schedules: cohort 1, every 8 hours, at 0, 8, and 16 hours; cohort 2, every 4 hours, at 0, 4, and 8 hours; and cohorts 3/4, every 2 hours, at 0, 2, and 4 hours.
The adverse events reported for sebetralstat were mild and comparable with those of placebo. There were no serious adverse events or study discontinuation during the trial.
KONFIDENT-S (NCT05505916) is an open-label extension trial evaluating the long-term (up to 2 years) safety of sebetralstat for on-demand treatment of HAE attacks in patients aged 12 years or older with HAE type I or II.
Reference
Iverson M, Duckworth E, Hansen E, et al. Rationale for the short-term prophylaxis regimen with sebetralstat in KONFIDENT-S. Presentation presented at the 13th C1 Inhibitor Deficiency and Angioedema Workshop; May 4-7, 2023; Budapest, Hungary.
