APEX 2 BCX7353 in Prevention of HAE Attacks
Research type
Research Study
Full title
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to evaluate the efficacy and safety of two dose levels of BCX7353 as an oral treatment for the prevention of attacks in subjects with Hereditary Angioedema.
IRAS ID
237389
Contact name
Melanie Cornpropst
Contact email
Sponsor organisation
BioCryst Pharmaceuticals Inc
Eudract number
2017-003966-29
Duration of Study in the UK
1 years, 8 months, 16 days
Research summary
Summary of Research
Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by periodic episodes of swelling of the skin, pharynx, larynx, gastrointestinal tract, genitals, and extremities. The frequency of these attacks varies between subjects, with attacks occurring rarely in some patients to as frequently as every few days in others. HAE attacks,which may or may not be precipitated by a stimulus (such as stress, trauma, or estrogen) are typically slow in onset,peaking in intensity within 24 hours, and gradually subside over the subsequent 5 days. BCX7353 is a synthetic small-molecule inhibitor of kallikrein that is being developed as an oral drug for the prevention of acute HAE attacks. Kallikrein is a known target for the prevention of HAE attacks.
A recently completed double blind placebo controlled study, BCX7353-203 (EudraCT: 2016-001272-29) has shown that BCX7353 significantly reduced the weekly rate of HAE attacks in HAE patients compared to placebo.
This study BCX7353-302 is a randomized, placebo-controlled, double-blind, parallel-group, 2-part study. In part 1, attack rate during 24 weeks prophylactic BCX7353 treatment at two dosage levels (150mg and 110mg) will be compared against placebo attack rates. Part 2 will evaluate long term safety of two dosage levels of BCX7353 - 150mg and 110mg per day.
Patients will complete diaries to document the attacks they have, and how they treat them. Patients will be allowed to treat their attacks as per normal clinical practice, without restriction.Summary of Results
A randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of BCX7353 (berotralstat) in patients with Hereditary Angioedema (HAE) for up to 240 weeks
BCX7353 was administered as a once daily oral dose, two doses were assessed during the study, 110mg and 150mg.
The study was split into three parts:
• Part 1 – Patients were randomly assigned to receive either BCX7353 110mg, BCX7353 150mg or Placebo for 24 weeks
• Part 2 – Patients receiving placebo were randomly assigned to receive either BCX7353 110mg or BCX7353 150mg for 24 weeks. Patients already receiving BCX7353 remained on their preassigned dose for 24 weeks
• Part 3 – All patients received BCX7353 150mg for up to 96 weeks
120 patients were treated in Part 1, 108 patients continued into Part 2 and 81 patients continued into Part 3.
Common adverse effects included nasopharyngitis, nausea headache, diarrhoea and abdominal pain.
Full results are published online and can be found using the following link: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbUglsYQ93JiRYt-2BaxLKZu7V2Ct9rJQ-2FsKhiYfHVb8B34CTL663kOQZI-2FO5y61hIeGw-3D-3DgEQs_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKcOnfZqDZTiSHvaYUp6TBeHAw5TcXOtuqVFZTt29QWK89E-2BZfduifCA7pc9t1MgM8SVXfvGxW-2Bhu2tvsRKeVnYkWlqbo-2BJ-2FPrQnNDVPAjyeA6WJURQe360CRtalGp6MUDCahCRedhnJOw-2FrlCWfAlQ1mFJLBH7uAyDQErCEXVoxH8ifWF6vBEisxuoHO4kdGM-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cd03f69c395844442b63108dae4d669b5%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638073906787823893%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=kcMAJNmfT1zXfinCzKUb1c7OIszTVU1nTCeA3WDdAVY%3D&reserved=0REC name
East of England - Essex Research Ethics Committee
REC reference
18/EE/0079
Date of REC Opinion
13 Apr 2018
REC opinion
Further Information Favourable Opinion