BioCryst Pharmaceuticals, Inc. has dosed the first subject in the APeX-1 clinical trial of BCX7353 for the oral treatment of HAE.
“We are very pleased that the adaptively-designed APeX-1 trial is now under way, and look forward to reporting Part 1 results around the end of 2016,” said William P Sheridan, SVP & Chief Medical Officer at BioCryst. “Results of the phase 1 study of ‘7353 support its potential to provide a normal life to HAE patients as a once-daily oral treatment by increasing kallikrein inhibition to normal levels.”
APeX-1 is a two part, Phase 2, randomized, double-blind, placebo-controlled dose ranging trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of BCX7353 as a preventative treatment to eliminate or reduce the frequency of angioedema attacks in HAE patients. Up to approximately 50 eligible subjects with HAE will be enrolled in the study.
“The APeX-1 trial is an exciting opportunity for the HAE patient community.” said Dr. Emel Aygören-Pürsün, M.D., Head of Angioedema Clinic, Goethe University Hospital Frankfurt/Main Pediatric Clinic, Frankfurt, Germany, and Principal Investigator for APeX-1. “The value of an effective and well tolerated oral preventive treatment for HAE patients cannot be overestimated.”
In part 1 of APeX-1, subjects with HAE will be randomized in a 1:1 ratio to receive an oral dose of either 350 mg of BCX7353 once daily or placebo once daily for four weeks. An interim analysis will be conducted after the first 24 subjects have completed treatment through study day 28. If a robust treatment effect is observed at the interim analysis, Part 2 of the study will be initiated. In the event the treatment effect is not well characterized with 24 subjects, a total of up to approximately 36 subjects will be enrolled in part 1. The sample size in Part 1 was kept flexible to cover a range of response options that would achieve 90 % power with an alpha of 0.05, based on reduction of attack rate of at least 70 % on BCX7353, placebo response rate of approximately 30%, and standard deviation of approximately 0.45 attacks per week.
To characterize dose-response in part 2 of APeX-1, 14 additional subjects with HAE will be randomized to 250mg of BCX7353 once daily (n=6), 125mg of BCX7353 once daily (n=6) or placebo (n=2).
The primary efficacy endpoint of APeX-1 is the number of angioedema attacks; attack rate per week, counts of attacks, proportion of subjects with no attacks, and number of attack-free days will be analyzed. Efficacy analyses will be conducted for HAE attacks reported over the entire dosing interval (Days 1 through 28) and during the dosing period in which plasma concentrations of BCX7353 should be at steady-state conditions (Days 8 through 28). Secondary efficacy endpoints include severity and duration of angioedema attacks, and measures of health-related quality of life. Safety will be characterized through evaluation of adverse events and laboratory testing. Pharmacokinetics and pharmacodynamic effects will be assessed through measurement of plasma drug levels and kallikrein inhibition.
Additional details regarding the APeX-1 trial design will be posted to www.clinicaltrials.gov.
Discovered by BioCryst, BCX7353 is a novel, once-daily, selective inhibitor of plasma kallikrein in development for the prevention of angioedema attacks in patients diagnosed with HAE. By inhibiting plasma kallikrein, BCX7353 suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients. BCX7353 has been generally safe and well tolerated in clinical pharmacology studies that have enrolled 117 healthy volunteers, 46 receiving single doses of up to 1000 mg, and 71 receiving once-daily doses of up to 500 mg for 7 days and 350 mg for 14 days. In the second week of study, approximately 5 % of healthy volunteers administered daily doses of ‘7353 for at least 7 days developed a drug-related skin rash that resolved within a few days.