Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II

Hereditary Angioedema Clinical Trial

— HAE CHAPTER-1  

Official title:

A Phase II, Double-blind, Placebo-controlled, Randomized, Dose-ranging, Parallel Group Study to Evaluate the Safety and Efficacy of PHA-022121 Administered Orally for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Due to C1-Inhibitor Deficiency (Type I or Type II)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05047185
• Other study ID #: PHA022121-C301
• Secondary ID: 2021-000227-13
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 19, 2022
• Est. completion date: December 2026

Study information

• Verified date: February 2024
• Source: Pharvaris Netherlands B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the safety and efficacy of PHA-022121 administered orally for prophylaxis against angioedema attacks in patients with hereditary angioedema (HAE). The study consists of 2 parts, with patients completing participation in Part 1 prior to initiation of treatment in Part 2. Part 1 of the study has 3 parallel arms and approximately 30 patients will be equally randomized to one of two dose regimens of PHA-022121 or matching placebo. Patients will continue to the single open-label arm in Part 2 of the study after completion of Part 1. The screening period is up to 8 weeks and the treatment periods are 12 weeks (Part 1) and 30 months (Part 2) in duration.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 34
• Est. completion date: December 2026
• Est. primary completion date: October 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Signed and dated informed consent form
• Diagnosis of HAE type I or II
• Documented history of at least 3 HAE attacks within the last 3 consecutive months prior to screening, or a minimum of 2 HAE attacks during the screening period
• Reliable access and experience to use standard of care acute attack medications

Exclusion Criteria:

• Pregnancy or breast-feeding
• Clinically significant abnormal electrocardiogram
• Any other systemic disease or significant disease or disorder that would interfere with the patient's safety or ability to participate in the study
• Use of C1-esterase inhibitor, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy within a defined period prior to enrolment
• Abnormal hepatic function
• Abnormal renal function
• History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
• Participation in any other investigational drug study within defined period

Related Conditions & MeSH terms

• Angioedema
• C1 Esterase Inhibitor Deficiency
• C1 Inhibitor Deficiency
• Hereditary Angioedema
• Hereditary Angioedema - Type 1
• Hereditary Angioedema - Type 2
• Hereditary Angioedema Attack
• Hereditary Angioedema Type I
• Hereditary Angioedema Type II
• Hereditary Angioedema Types I and II
• Hereditary Angioedema With C1 Esterase Inhibitor Deficiency

Intervention

Drug:
• Deucrictibant low dose
Deucrictibant softgel capsules for oral use (PHVS416)
• Deucrictibant high dose
Deucrictibant softgel capsules for oral use (PHVS416)
• Placebo
Matching placebo capsules for oral use

Locations

Country	Name	City	State
Austria	Study Site	Wien
Bulgaria	Study site	Sofia
Canada	Study site	Montréal	Quebec
Canada	Study site	Ottawa	Ontario
Germany	Study site	Berlin
Germany	Study site	Frankfurt
Ireland	Study site	Dublin
Italy	Study site	Milan
Italy	Study site	Padua	PD
Italy	Study site	Palermo
Poland	Study site	Kraków
United Kingdom	Study site	Brighton	England
United Kingdom	Study site	Bristol	England
United Kingdom	Study site	Cambridge	England
United Kingdom	Study site	London	England
United Kingdom	Study site	Southampton	England
United States	Study site	Birmingham	Alabama
United States	Study site	Paradise Valley	Arizona
United States	Study site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Pharvaris Netherlands B.V.

Countries where clinical trial is conducted

United States,  Austria,  Bulgaria,  Canada,  Germany,  Ireland,  Italy,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of investigator-confirmed HAE attacks		Day 0 to Day 84
Secondary	Number of investigator-confirmed moderate or severe HAE attacks during the treatment period		Day 0 to Day 84
Secondary	Number of investigator-confirmed HAE attacks requiring acute treatment during the treatment period		Day 0 to Day 84
Secondary	Number of patients achieving reduction in attack rate during the treatment period relative to baseline		Day 0 to Day 84
Secondary	Number of patients that are attack-free during the treatment period		Day 0 to Day 84
Secondary	Number and proportion of days with angioedema symptoms during the treatment period		Day 0 to Day 84
Secondary	Time to first investigator-confirmed HAE attack in the treatment period		Day 0 to Day 84
Secondary	Number of investigator-confirmed HAE attacks resulting in a visit to the emergency department or an admission to hospital		Day 0 to Day 84
Secondary	Number of investigator-confirmed angioedema attacks during the treatment period in Part 2.		Day 84 to Day 938
Secondary	Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period in Part 2.		Day 84 to Day 938
Secondary	Number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period in Part 2.		Day 84 to Day 938
Secondary	Incidence of HAE attacks during the treatment period in Part 2 (attack rate trend over time).		Day 84 to Day 938
Secondary	Number and proportion of days with angioedema symptoms during the treatment period in Part 2.		Day 84 to Day 938