The treatment candidate comes in the form of an oral suspension, a soft capsule (called PHVS416), or tablet (called PHVS719).
How does PHA121 work?
PHA121 is a small molecule that binds to the bradykinin B2 receptor, blocking bradykinin from activating it. Patients with HAE often have a low amount of an enzyme called C1 esterase inhibitor, which normally controls levels of bradykinin. Without sufficient C1 esterase inhibitors, the body produces too much bradykinin. This increases the permeability of blood vessels, leading to a leakage of fluids that results in swelling.
By binding to the bradykinin B2 receptor, PHA121 has the potential to stop HAE attacks and to prevent future attacks.
PHA121 in clinical trials
A double-blind, placebo-controlled and single-ascending dose Phase 1 clinical trial in 68 healthy volunteers investigated the safety, tolerability, and pharmacokinetics (movement in the body) of an oral solution of PHA121.
Researchers randomized participants to either the treatment (52 participants) or a placebo (16 participants). All were monitored for 72 hours after taking a single dose of PHA121.
They found that doses of 12 and 22 mg of PHA121 maintained their desired therapeutic blood levels for 12 hours. Participants tolerated well all tested dose levels, with similar percentages of mild and temporary adverse events reported in both the treatment and the placebo groups. Researchers presented trial results at the 2020 American College of Asthma, Allergy, and Immunology (ACAAI) Annual Scientific Meeting.
Ongoing clinical trials
PHA121 will be further studied in a Phase 2 clinical trial, called RAPIDe-1 (NCT04618211). The study, due to open at sites in Canada in January 2021, aims to recruit 54 adults, ages 18 to 75, with HAE type 1 or 2.
Participants will receive one of three escalating doses of PHVS416 or a placebo. In the first part of the study, patients will receive a single dose of the treatment at the study center during a period when they are not experiencing an HAE attack, in order to asses the pharmacokinetics of the oral capsules. In its second part, patients will self-administer either the treatment or a placebo at home during three HAE attacks.
The trial’s primary outcome is the change in scores on the three-symptom composite visual analogue scale (VAS-3), which looks at skin pain, skin swelling, and abdominal pain. Researchers will also collect data on the time to symptom relief, as well as patients’ degree of satisfaction and adverse events.
Last updated: Dec. 17, 2020
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