Preparations underway for Phase 3 trial of deucrictibant
HAE treatment to be tested in 81 patients over 6 months
Regulatory authorities in Japan, the U.S., and the European Union have aligned on plans for a Phase 3 clinical trial to test the oral medication deucrictibant as a prophylactic (preventive) treatment to reduce the risk of swelling attacks in people with hereditary angioedema (HAE).
With alignment from the U.S. Food and Drug Administration (FDA), the European Union Committee for Medicinal Products for Human Use, and the Japanese Pharmaceuticals and Medical Devices Agency, deucrictibant’s developer Pharvaris is preparing to launch the Phase 3 trial, which will be called CHAPTER-3.
CHAPTER-3 aims to enroll about 81 HAE patients, ages 12 and older, who will be randomly assigned to receive either deucrictibant in the form of extended-release tablets (40 mg/day) or a placebo, once daily, for 24 weeks (about six months).
The study’s main goal is to assess deucrictibant’s ability to reduce the number of HAE attacks over the course of the treatment period. Other goals include assessing the therapy’s safety, pharmacological properties, and impact on patients’ health-related quality of life.
“Pharvaris supports the view of the HAE community that achievement of complete control of the disease and normalization of lives of people with HAE through long-term prophylaxis are the main goals of treatment in HAE,” Berndt Modig, CEO of Pharvaris, said in a company press release. “Obtaining alignment with regulatory agencies on our proposed global clinical development plan for deucrictibant as a prophylactic HAE treatment is an important milestone for the company.”
Separate trial ongoing
Earlier this year, Pharvaris launched a separate Phase 3 trial, RAPIDe-3 (NCT06343779), which is testing an immediate-release formulation of deucrictibant called PHVS416 as an on-demand treatment to manage HAE attacks. Enrollment in that study is “progressing as planned, and CHAPTER-3 start-up activities are underway globally,” Modig said.
RAPIDe-3 is open to people with HAE types 1 and 2, ages 12 through 75, who have had at least two HAE attacks in the three months before entering the study. Patients taking other prophylactic therapies must be on a stable dose. Recruitment is ongoing at a dozen sites across the mainland U.S., Puerto Rico, South Korea, and Germany.
“Diligent execution of the RAPIDe-3 and the CHAPTER-3 pivotal clinical studies remains our top priority, with the goal of establishing differentiated data packages for deucrictibant in both on-demand and prophylaxis,” Modig said.
In HAE, swelling attacks are caused by abnormally high levels of a signaling molecule called bradykinin. Deucrictibant is designed to block receptors for this signaling molecule, controlling swelling.
A previous Phase 2 trial called CHAPTER-1 (NCT05047185) indicated that prophylactic treatment with deucrictibant could help prevent swelling attacks, while a separate Phase 2 study dubbed RAPIDe-1 (NCT04618211) found that on-demand treatment with deucrictibant was effective for resolving swelling attacks.
The Phase 3 trials CHAPTER-3 and RAPIDe-3 aim to confirm the efficacy shown in those earlier studies.
Modig said further data from the Phase 2 trials, as well as findings from their ongoing extension studies, will be presented at “upcoming medical meetings.”
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