Clinical trial NCT05047185: Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hereditary Angioedema
Hereditary Angioedema Type I
Hereditary Angioedema Type II
Hereditary Angioedema Types I and II
Hereditary Angioedema Attack
Hereditary Angioedema With C1 Esterase Inhibitor Deficiency
Hereditary Angioedema - Type 1
Hereditary Angioedema - Type 2
C1 Esterase Inhibitor Deficiency
C1 Inhibitor Deficiency
Keywords: HAE
HAE Type I
HAE Type II
Oral Treatment
Bradykinin B2 Receptor Antagonist
PHVS416
PHA121
Prophylaxis
Deucrictibant
Lead sponsor: Pharvaris Netherlands B.V.
Sponsor class: INDUSTRY
First posted: 2021-09-17
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of investigator-confirmed HAE attacks
timeFrame: Day 0 to Day 84
Secondary outcomes:
measure: Number of investigator-confirmed moderate or severe HAE attacks during the treatment period
timeFrame: Day 0 to Day 84
measure: Number of investigator-confirmed HAE attacks requiring acute treatment during the treatment period
timeFrame: Day 0 to Day 84
measure: Number of patients achieving reduction in attack rate during the treatment period relative to baseline
timeFrame: Day 0 to Day 84
measure: Number of patients that are attack-free during the treatment period
timeFrame: Day 0 to Day 84
measure: Number and proportion of days with angioedema symptoms during the treatment period
timeFrame: Day 0 to Day 84
measure: Time to first investigator-confirmed HAE attack in the treatment period
timeFrame: Day 0 to Day 84
measure: Number of investigator-confirmed HAE attacks resulting in a visit to the emergency department or an admission to hospital
timeFrame: Day 0 to Day 84
measure: Number of investigator-confirmed angioedema attacks during the treatment period in Part 2.
timeFrame: Day 84 to Day 938
measure: Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period in Part 2.
timeFrame: Day 84 to Day 938
measure: Number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period in Part 2.
timeFrame: Day 84 to Day 938
measure: Incidence of HAE attacks during the treatment period in Part 2 (attack rate trend over time).
timeFrame: Day 84 to Day 938
measure: Number and proportion of days with angioedema symptoms during the treatment period in Part 2.
timeFrame: Day 84 to Day 938
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Study site
state: Alabama
city: Paradise Valley
country: United States
facility: Study site
state: Arizona
city: Saint Louis
country: United States
facility: Study site
state: Missouri
city: Wien
country: Austria
facility: Study Site
city: Sofia
country: Bulgaria
facility: Study site
city: Ottawa
country: Canada
facility: Study site
state: Ontario
city: Montréal
country: Canada
facility: Study site
state: Quebec
city: Berlin
country: Germany
facility: Study site
city: Frankfurt
country: Germany
facility: Study site
city: Dublin
country: Ireland
facility: Study site
city: Padua
country: Italy
facility: Study site
state: PD
city: Milan
country: Italy
facility: Study site
city: Palermo
country: Italy
facility: Study site
city: Kraków
country: Poland
facility: Study site
city: Brighton
country: United Kingdom
facility: Study site
state: England
city: Bristol
country: United Kingdom
facility: Study site
state: England
city: Cambridge
country: United Kingdom
facility: Study site
state: England
city: London
country: United Kingdom
facility: Study site
state: England
city: Southampton
country: United Kingdom
facility: Study site
state: England
Study officials:
affiliation: UC San Diego, La Jolla, California, United States
name: Marc Riedl, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Frankfurt - Goethe University, Frankfurt, Germany
name: Emel Aygören-Pürsün, MD
role: PRINCIPAL_INVESTIGATOR
References: