Pharvaris starts Phase 3 trial of deucrictibant as on-demand therapy
RAPIDe-3 to test an immediate-release capsule formulation in 120 HAE patients
Pharvaris has started a Phase 3 clinical trial called RAPIDe-3 to test an immediate-release capsule formulation of deucrictibant as an on-demand treatment to manage swelling attacks in hereditary angioedema (HAE).
“We hear from the HAE community that rapid onset and complete resolution of angioedema attacks with a single, easy-to-administer oral pill remains a high unmet need,” Peng Lu, MD, PhD, Pharvaris’ chief medical officer, said in a company press release. “The RAPIDe-3 study is designed to assess the effectiveness of deucrictibant in addressing that unmet need.”
Pharvaris presented the design of the trial, which was developed with input from the U.S. Food and Drug Administration (FDA), in posters at two recent conferences: the third National Congress of the Italian Network for Hereditary and Acquired Angioedema (ITACA) and the 2024 HAE International Regional Conference Americas.
RAPIDe-3 to enroll 120 people, ages 12-75, with HAE types 1 or 2
The RAPIDe-3 study is expected to enroll approximately 120 people, ages 12 to 75, with HAE types 1 or 2.
To be eligible, participants must have experienced at least two swelling attacks in the three months before screening and be comfortable using on-demand treatments for HAE attacks. Patients taking a long-term prophylactic (preventive) therapy must have been on steady treatment for at least six months. They must also not use attenuated androgens for short-term prophylaxis in the month before entering the trial. The study will not include patients who are pregnant or breastfeeding.
During the study, all participants will self-administer deucrictibant or a placebo for two swelling attacks in a random order. One attack will be treated with 20 mg immediate-release deucrictibant (also known as PHVS416), and the other with a placebo.
For each attack, patients are allowed to administer a second dose of the study drug if symptoms persist or continue worsening for at least four hours after the first dose. If symptoms are still present or continue to get worse for another hour after that, additional on-demand treatment to resolve the attack can be given. A few days after each treated attack, patients will meet with care providers (virtually or in person) to assess side effects and any other issues.
The main goal of RAPIDe-3 is to see if PHVS416 can outperform a placebo in its ability to shorten the time to onset of symptom relief, or the earliest point that patients consistently start rating their symptoms as being at least “a little better.” This will be evaluated within a timeframe of 12 hours following treatment.
We hear from the HAE community that rapid onset and complete resolution of angioedema attacks with a single, easy-to-administer oral pill remains a high unmet need.
RAPIDe-3 will test deucrictibant’s safety, ability to hasten end of progression
The study will also assess the therapy’s safety profile, as well as a range of other efficacy-related measures, including the time to end of progression, which refers to the period when symptoms stop getting worse (even if they aren’t yet resolving). Investigators will assess the proportion of attacks resolving with a single therapy dose within a timeframe of 24 hours. The treatment’s impact on patients’ quality of life will also be evaluated as an exploratory goal.
“To our knowledge, Pharvaris has been the first and only company to include and statistically power the novel endpoint ‘End of Progression’ in a pivotal study,” Lu said, adding this measurement “could differentiate deucrictibant from other HAE therapies.”
In an earlier Phase 2 clinical trial called RAPIDe-1 (NCT04618211), on-demand PHVS416 outperformed a placebo in its ability to effectively hasten both symptom relief and end of progression. The Phase 3 trial, which is larger and has greater statistical power to detect meaningful results, aims to confirm those early findings.
Patients who complete RAPIDe-3 will be eligible to continue treatment with deucrictibant in an open-label extension study, provided inclusion and exclusion criteria are met.
Deucrictibant works to block receptors for bradykinin, the signaling molecule that’s thought to drive swelling attacks in HAE. Pharvaris is developing the experimental therapy both as an on-demand treatment for HAE attacks and as a prophylactic treatment.
Pharvaris recently restarted open-label extension of Phase 2 CHAPTER-1 trial
The company recently restarted the open-label extension of its Phase 2 CHAPTER-1 clinical trial (NCT05047185) testing prophylactic deucrictibant, after the FDA lifted a hold that had been put in place due to concerns raised by its review of preclinical studies.
“In collaboration with regulatory authorities we have designed a robust global study to assess the efficacy and safety of deucrictibant, a molecule which we believe has the potential to be best-in-class for both the prevention and treatment of HAE attacks,” said Berndt Modig, CEO of Pharvaris.
CHAPTER-1 evaluated the safety and efficacy of prophylactic treatment with deucrictibant against a placebo for about three months in 34 adults with HAE. Results indicated the therapy significantly lowered the risk of swelling attacks. In a separate poster presented at the ITACA meeting, Pharvaris showcased new data from CHAPTER-1 highlighting the treatment’s effect on life quality.
Specifically, data showed that all but one patient given the experimental therapy reported improvements in scores on the Patient Global Assessment of Change, a general measure of life quality, after about three months. By comparison, most patients given a placebo had no change in scores during the study.
Most patients given deucrictibant also reported improvements on a disease-specific life quality measure called the Angioedema Quality of Life questionnaire, whereas scores were minimally changed for those on a placebo.
These data “provide evidence that prophylactic treatment with oral deucrictibant for 12 weeks improved [health-related quality of life] for people living with HAE,” researchers concluded, adding the findings “support further development of deucrictibant as a potential prophylactic therapy for HAE.”
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