Clinical trial NCT04618211: Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema
Official title: A Phase II, Double-blind, Placebo-controlled, Randomized, Cross-over, Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema Due to C1-inhibitor Deficiency Type I and II
Study type: INTERVENTIONAL
Overall status: COMPLETED
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 Antagonists
PHVS416
PHA121
PHA-022121
Deucrictibant
Lead sponsor: Pharvaris Netherlands B.V.
Sponsor class: INDUSTRY
First posted: 2020-11-05
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study evaluates the efficacy of orally administered deucrictibant for the acute treatment of attacks in patients with hereditary angioedema (HAE). Eligible subjects are randomized to one of three single doses of deucrictibant and placebo. The study will compare symptom relief (skin pain, skin swelling, abdominal pain) during HAE attacks and safety of each dose of deucrictibant with placebo.

Detailed description: In Part I of the study, patients in non-attack state receive the assigned active single dose of deucrictibant at the study center to assess pharmacokinetics (the way the body absorbs, distributes, and gets rid of the drug) and safety. In Part II of the study, patients self-administer blinded study drug at home to treat three HAE attacks with deucrictibant or placebo (cross-over).

Eligibility criteria: Key Inclusion Criteria:

1. Signed and dated informed consent form
2. Diagnosis of HAE type I or II
3. Documented history of HAE attacks: at least three in the last 4 months, or at least two in the last 2 months prior to screening
4. Reliable access and experience to use standard of care acute attack medications

Key Exclusion Criteria:

1. Pregnancy or breast-feeding
2. Clinically significant abnormal electrocardiogram
3. Any other systemic disease or significant disease or disorder that would interfere with the patient's safety or ability to participate in the study
4. Use of C1-esterase inhibitor, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy within a defined period prior to enrollment
5. Positive serology for HIV or active infection with hepatitis B virus or hepatitis C virus
6. Abnormal hepatic function
7. Abnormal renal function
8. History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
9. History of documented severe hypersensitivity to any medicinal product
10. Participation in any other investigational drug study within defined period

Primary outcomes:
measure: Change of the 3-symptom composite visual analogue scale (VAS-3) score from pre-treatment to 4 hours post-treatment
timeFrame: Pre-treatment and 4 hours post-treatment
Secondary outcomes:
measure: Time to onset of symptom relief by visual analogue scale (VAS-3) score
timeFrame: Assessed from pre-treatment to 48 hours post-treatment
measure: Proportion of study drug treated attacks requiring HAE rescue medication
timeFrame: Assessed at 4 hours post-study drug treatment
measure: Time to onset of almost complete and complete symptom relief by visual analogue scale (VAS-3)
timeFrame: Assessed from pre-treatment to 48 hours post-treatment
measure: Mean symptom complex severity (MSCS) score
timeFrame: 4 hours post-treatment
measure: Treatment outcome score (TOS)
timeFrame: Pre-treatment and 4 hours post-treatment
measure: Treatment satisfaction questionnaire for medication (TSQM) scores
timeFrame: 48 hours post-treatment
measure: Treatment-emergent adverse events (TEAEs)
timeFrame: From post-dose non-attack visit through study completion, approximately 26 weeks
measure: Treatment-related adverse events (AEs)
timeFrame: From post-dose non-attack visit through study completion, approximately 26 weeks
measure: Treatment-emergent serious adverse events (TESAEs)
timeFrame: From post-dose non-attack visit through study completion, approximately 26 weeks
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: San Diego
country: United States
facility: Study site
state: California
city: Santa Monica
country: United States
facility: Study site
state: California
city: Walnut Creek
country: United States
facility: Study site
state: California
city: Chevy Chase
country: United States
facility: Study site
state: Maryland
city: Saint Louis
country: United States
facility: Study site
state: Missouri
city: Hershey
country: United States
facility: Study site
state: Pennsylvania
city: Sofia
country: Bulgaria
facility: Study site
city: Edmonton
country: Canada
facility: Study site
state: Alberta
city: Ottawa
country: Canada
facility: Study site
state: Ontario
city: Toronto
country: Canada
facility: Study site
state: Ontario
city: Montréal
country: Canada
facility: Study site
state: Quebec
city: Québec City
country: Canada
facility: Study site
state: Quebec
city: Brno
country: Czechia
facility: Study site
city: Hradec Králové
country: Czechia
facility: Study site
city: Grenoble
country: France
facility: Study site
city: Montpellier
country: France
facility: Study site
city: Paris
country: France
facility: Study site
city: Berlin
country: Germany
facility: Study site
city: Dresden
country: Germany
facility: Study site
city: Frankfurt
country: Germany
facility: Study site
city: Mainz
country: Germany
facility: Study site
city: Ulm
country: Germany
facility: Study site
city: Budapest
country: Hungary
facility: Study site
city: Ashkelon
country: Israel
facility: Study site
city: Haifa
country: Israel
facility: Study site
city: Tel Aviv
country: Israel
facility: Study site
city: Monserrato
country: Italy
facility: Study site
city: Naples
country: Italy
facility: Study site
city: Amsterdam
country: Netherlands
facility: Study site
city: Kraków
country: Poland
facility: Study site
city: Barcelona
country: Spain
facility: Study site
city: Madrid
country: Spain
facility: Study site
city: Brighton
country: United Kingdom
facility: Study site
city: London
country: United Kingdom
facility: Study site
Study officials:
affiliation: Charite University, Berlin, Germany
name: Marcus Maurer, Prof MD
role: PRINCIPAL_INVESTIGATOR
References: