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

Pharvaris Netherlands B.V.34 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

Conditions

Hereditary Angioedema Hereditary Angioedema Type I Hereditary Angioedema Type II Hereditary Angioedema Types I and II

Interventions

Deucrictibant low doseDRUG

Deucrictibant softgel capsules for oral use (PHVS416)

Deucrictibant high doseDRUG

Deucrictibant softgel capsules for oral use (PHVS416)

PlaceboDRUG

Matching placebo capsules for oral use

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (19)

Study site

Birmingham, Alabama, United States

Study site

Paradise Valley, Arizona, United States

Study site

St Louis, Missouri, United States

Study Site

Vienna, Austria

Study site

Sofia, Bulgaria

Study site

Ottawa, Ontario, Canada

Study site

Montreal, Quebec, Canada

Study site

Berlin, Germany

Study site

Frankfurt, Germany

Study site

Dublin, Ireland

...and 9 more locations

Outcomes

Primary Outcomes

Number of investigator-confirmed HAE attacks

Time frame: Day 0 to Day 84

Secondary Outcomes

Number of investigator-confirmed moderate or severe HAE attacks during the treatment period

Time frame: Day 0 to Day 84

Number of investigator-confirmed HAE attacks requiring acute treatment during the treatment period

Time frame: Day 0 to Day 84

Number of patients achieving reduction in attack rate during the treatment period relative to baseline

Time frame: Day 0 to Day 84

Number of patients that are attack-free during the treatment period

Time frame: Day 0 to Day 84

Number and proportion of days with angioedema symptoms during the treatment period

Time frame: Day 0 to Day 84

Time to first investigator-confirmed HAE attack in the treatment period

Time frame: Day 0 to Day 84

Number of investigator-confirmed HAE attacks resulting in a visit to the emergency department or an admission to hospital

Time frame: Day 0 to Day 84

Number of investigator-confirmed angioedema attacks during the treatment period in Part 2.

Time frame: Day 84 to Day 938

Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period in Part 2.

Time frame: Day 84 to Day 938

Number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period in Part 2.

Time frame: Day 84 to Day 938

Incidence of HAE attacks during the treatment period in Part 2 (attack rate trend over time).

Time frame: Day 84 to Day 938

Number and proportion of days with angioedema symptoms during the treatment period in Part 2.

Time frame: Day 84 to Day 938