Clinical trial NCT05396105: Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema
Official title: A Phase II/III, Extension Study of Orally Administered PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
PHASE3
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 [C1-INH] Deficiency
C1 Esterase Inhibitor Deficiency
C1 Esterase Inhibitor, Deficiency of
C1 Inhibitor Deficiency
Hereditary Angioedema Type III
Hereditary Angioedema (HAE)
Hereditary Angioedema Type I and II
Keywords: HAE
HAE Type I
HAE Type II
Oral Treatment
Bradykinin B2 Receptor Antagonists
On-Demand
PHA121
PHVS416
PHA-022121
Deucrictibant
HAE Type III
Lead sponsor: Pharvaris Netherlands B.V.
Sponsor class: INDUSTRY
First posted: 2022-05-31
Enrollment: 140
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluates the safety and efficacy of long-term on-demand treatment with orally administered deucrictibant for acute hereditary angioedema (HAE) attacks, including laryngeal attacks. The study will enroll patients from Study PHA022121-C201 (NCT04618211) and Study PHA022121-C306 (NCT06343779) who elect to participate in this extension study and meet the eligibility requirements.

Detailed description: Part A of the study will enroll adult participants from Study PHA022121-C201. The double-blind treatment assignment from Study PHA022121-C201 will be maintained.

Part B will include participants rolling over from Part A and additionally enroll participants from Study PHA022121-C201 who did not participate in Part A, and participants from Study PHA022121-C306 who elect to participate in this extension study and meet the eligibility requirements.

Eligibility criteria: Key Inclusion Criteria:

1. Provision of written informed consent. If the participant is a minor (i.e., \<18 years of age or as determined by local law), consent will be obtained from the participant's parent/legally designated representative/guardian and written assent will be obtained from the participant, per country regulations.
2. For participants from Study C201, received at least one dose of study drug (including the non-attack visit) in Study C201. For participants from Study C306, participant was randomized (and for adolescent participants 12 to \<18 years received a dose of study drug in a non-attack state at Visit 1) and completed Study C306, with 2 attacks treated, or after closure of that study by the Sponsor.

   Enrollment of adolescents (≥12 to \<18 years or age of adulthood as defined locally) from these studies is with consideration of local age requirements.
3. Female participants of childbearing potential (or who become of childbearing potential during the study) must agree to the protocol-specified pregnancy testing and to be abstinent from heterosexual intercourse or to use an acceptable contraception method as defined in the protocol and as available locally from enrollment until 30 days after the last study drug administration.
4. In the opinion of the Investigator, the participant (and parent/caregiver for adolescent participants) is willing and able to comply with the protocol.

Key Exclusion Criteria:

1. Any female who is pregnant, plans to become pregnant, or is breast-feeding.
2. Any other systemic disease (e.g., cardiovascular, gastrointestinal, renal, respiratory, neurological) or significant disease or disorder that, in the opinion of the Investigator, would interfere with the participant's safety or ability to participate in the study.
3. Use of lanadelumab for long-term HAE prophylactic therapy within 12 weeks prior to enrollment in Part A.
4. For Part A: Use of C1-esterase inhibitor, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy within a defined period prior to enrolment.

   For Part B: If a participant is receiving long-term prophylactic therapy with one of the following medications indicated for HAE: plasma-derived C1-INH, danazol at less than or equal to 200 mg/day, anti-fibrinolytics, berotralstat, or lanadelumab, they must be on a stable dose and regimen for at least 3 months before screening and intends to remain on the same dose for the duration of the study.
5. History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
6. Participation in any other investigational drug study within defined period
7. Discontinued from parent study after enrollment for any study drug-related safety reason or non-compliance including significant protocol deviation.
8. Use of concomitant medications that are strong CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole, ritonavir) or strong CYP3A4 inducers (e.g., carbamazepine and phenytoin).

Primary outcomes:
measure: Treatment-emergent Adverse Events (TEAEs), treatment-related TEAEs, treatment-emergent serious adverse events (TESAEs), treatment-related TESAEs, and TEAEs leading to deucrictibant discontinuation
timeFrame: From enrollment through study completion, up to 54 months (dependent on time of enrollment).
measure: Heart Rate
timeFrame: From enrollment through study completion, up to 54 months (dependent on time of enrollment).
measure: Blood pressure
timeFrame: From enrollment through study completion, up to 54 months (dependent on time of enrollment).
measure: Body temperature
timeFrame: From enrollment through study completion, up to 54 months (dependent on time of enrollment).
measure: Clinical laboratory tests
timeFrame: From enrollment through study completion, up to 54 months (dependent on time of enrollment).
measure: Electrocardiograms
timeFrame: From enrollment through study completion, up to 54 months (dependent on time of enrollment).
measure: Physical Examination
timeFrame: From enrollment through study completion, up to 54 months (dependent on time of enrollment).
Secondary outcomes:
measure: Time to onset of symptom relief, defined as Patient Global Impression of Change (PGI-C) rating of at least "a little better" for 2 consecutive timepoints within 12 hours post-treatment
timeFrame: Assessed from 1 hour to 12 hours post-treatment
measure: Time to substantial symptom relief, defined as achieving PGI-C rating of at least "better" for 2 consecutive timepoints within 12 hours post-treatment
timeFrame: Assessed from 1 hour to 12 hours post-treatment
measure: Time to substantial symptom relief by Patient Global Impression of Severity (PGI-S), defined as achieving ≥1 point reduction in PGI-S from pre-treatment for 2 consecutive timepoints within 12 hours post-treatment
timeFrame: Assessed from pre-treatment to 12 hours post-treatment
measure: Time to onset of symptom relief by VAS-3/VAS-5 (Part A) or AMRA (Part B), defined as a reduction of ≥30% from pretreatment in VAS/AMRA composite score, sustained for 2 consecutive timepoints)
timeFrame: Assessed from pre-treatment to 48 hours post-treatment
measure: Time to symptom relief by VAS (Part A) or AMRA (Part B), based on achieving ≥50% reduction from pretreatment in VAS/AMRA composite score sustained for 2 consecutive timepoints.
timeFrame: Assessed from pre-treatment to 48 hours post-treatment
measure: Proportion of deucrictibant-treated attacks requiring rescue medication within 24 hours post-treatment
timeFrame: Assessed from pre-treatment to 24 hours post-treatment
measure: Proportion of deucrictibant-treated attacks with almost complete or complete symptom relief by VAS-3/ VAS-5/ AMRA through 24 hours post-treatment
timeFrame: Assessed from pre-treatment to 24 hours post-treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Study site
state: Alabama
city: Scottsdale
country: United States
facility: Study site
state: Arizona
city: Little Rock
country: United States
facility: Study site
state: Arkansas
city: Santa Monica
country: United States
facility: Study site
state: California
city: Walnut Creek
country: United States
facility: Study site
state: California
city: Colorado Springs
country: United States
facility: Study site
state: Colorado
city: Chevy Chase
country: United States
facility: Study site
state: Maryland
city: Detroit
country: United States
facility: Study site
state: Michigan
city: St. Louis
country: United States
facility: Study site
state: Missouri
city: Hershey
country: United States
facility: Study site
state: Pennsylvania
city: Dallas
country: United States
facility: Study site
state: Texas
city: Buenos Aires
country: Argentina
facility: Study site
city: Campbelltown
country: Australia
facility: Study site
state: New South Wales
city: Graz
country: Austria
facility: Study site
city: Wien
country: Austria
facility: Study site
city: Sofia
country: Bulgaria
facility: Study site
city: Sofia
country: Bulgaria
facility: Study site
city: Edmonton
country: Canada
facility: Study site
state: Alberta
city: Montréal
country: Canada
facility: Study site
state: Quebec
city: Brno
country: Czechia
facility: Study site
city: Grenoble
country: France
facility: Study site
city: Paris
country: France
facility: Study site
city: Berlin
country: Germany
facility: Study site
city: Frankfurt am Main
country: Germany
facility: Study site
city: Lubeck
country: Germany
facility: Study site
city: Hong Kong
country: Hong Kong
facility: Study site
city: Budapest
country: Hungary
facility: Study site
city: Ashkelon
country: Israel
facility: Study site
city: Catania
country: Italy
facility: Study site
city: Milano
country: Italy
facility: Study site
city: Milano
country: Italy
facility: Study site
city: Napoli
country: Italy
facility: Study site
city: Padova
country: Italy
facility: Study site
city: Palermo
country: Italy
facility: Study site
city: Roma
country: Italy
facility: Study site
city: Hiroshima
country: Japan
facility: Study site
city: Kanagawa
country: Japan
facility: Study site
city: Osaka
country: Japan
facility: Study site
city: Tokyo
country: Japan
facility: Study site
city: Tokyo
country: Japan
facility: Study site
city: Daegu
country: Korea, Republic of
facility: Study site
city: Seoul
country: Korea, Republic of
facility: Study site
city: Amsterdam
country: Netherlands
facility: Study site
city: Kraków
country: Poland
facility: Study site
city: San Juan
country: Puerto Rico
facility: Study site
city: San Juan
country: Puerto Rico
facility: Study site
city: Cape Town
country: South Africa
facility: Study site
city: Barcelona
country: Spain
facility: Study site
city: Barcelona
country: Spain
facility: Study site
city: Madrid
country: Spain
facility: Study site
city: Lund
country: Sweden
facility: Study site
city: Ankara
country: Turkey
facility: Study site
city: Istanbul
country: Turkey
facility: Study site
Study officials:
affiliation: Pharvaris Netherlands B.V.
name: Study Director
role: STUDY_DIRECTOR
References: