Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema

NCT05396105 | Enrolling By Invitation Phase 2 FDA Drug

• 2 other identifiers: PHA022121-C3032023-505766-28-00
• Study Type: interventional
• Target: 150
• Locations: 24 countries
• Sites: 61

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 participants from Study PHA022121-C201 (NCT04618211), Study PHA022121-C306 (NCT06343779) and deucrictibant treatment naïve HAE-nC1INH adult participants who elect to participate in this extension study and meet the eligibility requirements.

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; Hereditary Angioedema - Type 3; 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; HAE-nC1INH

Outcome Measures

Primary Outcomes (7)

• Treatment-emergent Adverse Events (TEAEs), treatment-related TEAEs, treatment-emergent serious adverse events (TESAEs), treatment-related TESAEs, and TEAEs leading to deucrictibant discontinuation

  From enrollment through study completion, up to 54 months (dependent on time of enrollment).

• Heart Rate

  Descriptive in nature, no formal statistical hypothesis testing will be performed.

  From enrollment through study completion, up to 54 months (dependent on time of enrollment).

• Blood pressure

  Systolic and diastolic blood pressure will be measured. Descriptive in nature, no formal statistical hypothesis testing will be performed.

  From enrollment through study completion, up to 54 months (dependent on time of enrollment).

• Body temperature

  Descriptive in nature, no formal statistical hypothesis testing will be performed.

  From enrollment through study completion, up to 54 months (dependent on time of enrollment).

• Clinical laboratory tests

  hematology, blood chemistry, urinalysis

  From enrollment through study completion, up to 54 months (dependent on time of enrollment).

• Electrocardiograms

  From enrollment through study completion, up to 54 months (dependent on time of enrollment).

• Physical Examination

  From enrollment through study completion, up to 54 months (dependent on time of enrollment).

Secondary Outcomes (8)

• 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

  Assessed from 1 hour to 12 hours post-treatment

• Time to substantial symptom relief, defined as achieving PGI-C rating of at least "better" for 2 consecutive timepoints within 12 hours post-treatment

  Assessed from 1 hour to 12 hours post-treatment

• 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

  Assessed from pre-treatment to 12 hours post-treatment

• Proportion of attacks achieving symptom resolution, defined as achieving PGI-S rating of "none" at 24 hours post-treatment.

  At 24 hours post-treatment

• Proportion of deucrictibant-treated attacks requiring rescue medication within 24 hours post-treatment

  Assessed from pre-treatment to 24 hours post-treatment

Study Arms (2)

Part A: Deucrictibant, blinded dose

EXPERIMENTAL

Participants will receive the dose of deucrictibant they were randomized to in the PHA022121-C201 study (low, medium, or high dose, each consisting of 3 capsules of deucrictibant or matching placebo) for oral use for on-demand treatment of HAE attacks.

Drug: deucrictibant

Part B: Deucrictibant, open-label

EXPERIMENTAL

Participants will receive deucrictibant soft capsules for oral use for on-demand treatment of HAE attacks.

Drug: deucrictibant

Interventions

deucrictibant DRUG

3 capsules of deucrictibant or matching placebo will be administered orally for each HAE attack

Also known as: PHVS416, PHA121, PHA-022121

Part A: Deucrictibant, blinded dose

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of the signed informed consent form by the participant and/ or legally designated representative. 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 signed assent will be obtained from the participant, per country regulations.
• 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.
• 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.
• In the opinion of the Investigator, the participant (and parent/caregiver for adolescent participants) is willing and able to comply with the protocol.
• Adult participants with HAE type 3 (HAE-nC1INH) who are deucrictibant-treatment naïve, must have:
• Recurrent angioedema attacks with diagnostic testing results obtained during screening to confirm C1INH function ≥50% of normal and C4 level not below the lower level of the normal range performed by the central laboratory.
• Documented genetic mutation associated with HAE-nC1INH as listed in the Hereditary Angioedema Association (HAEA) and World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) Guidelines.
• Attacks not responding to treatments with high-dose antihistamine (cetirizine 40 mg/day or equivalent high-dose second-generation antihistamine medication) and no clinical attack symptoms relief if treated with corticosteroid, montelukast, or omalizumab
• Documented effective attack symptom relief with on-demand icatibant treatment
• A history of at least 1 HAE attack in the last 3 months prior to Screening

You may not qualify if:

• Any female who is pregnant, plans to become pregnant, or is breast-feeding.
• 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.
• Use of lanadelumab for long-term HAE prophylactic therapy within 12 weeks prior to enrollment in Part A.
• Participants who have recently used short or long-term HAE prophylaxis or on-demand HAE treatment will not be excluded from the study provided the following washout period is observed (i.e., study screening or enrollment/rollover should be delayed allowing for washout):
• For Part A:
• week washout period before enrollment should be respected for participants who have used any C1-INH product, oral kallikrein inhibitors, attenuated androgens, or anti-fibrinolytics for long-term prophylactic HAE therapy.
• week washout period before enrollment should be respected for participants who have used plasma derived C1-INH concentrates (Berinert, Cinryze, Haegarda) for on-demand treatment or short-term prophylaxis.
• hour washout period before enrollment should be respected for participants who have used recombinant C1-INH (Ruconest) for on-demand treatment or short-term prophylaxis.
• For Part B:
• If a participant is receiving long-term prophylactic therapy with one of the following medications indicated for HAE: plasma-derived C1INH, 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.
• History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse
• Participation in any other investigational drug study within (except with deucrictibant) currently, within the last 30 days prior to the first deucrictibant dose or within 5 half-lives of study drug at enrollment, whichever is longer.
• Discontinued from parent study after enrollment for any study drug-related safety reason or non-compliance including significant protocol deviation.
• 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).

Sponsors & Collaborators

• Pharvaris Netherlands B.V.: lead

Study Sites (63)

Study site

Birmingham, Alabama, 35209, United States

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Scottsdale, Arizona, 85258, United States

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Little Rock, Arkansas, 72205, United States

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San Diego, California, 92122, United States

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Santa Monica, California, 90404, United States

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Walnut Creek, California, 94598, United States

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Colorado Springs, Colorado, 80907, United States

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Chevy Chase, Maryland, 20815, United States

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Boston, Massachusetts, 02115, United States

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Detroit, Michigan, 48202, United States

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St Louis, Missouri, 63141, United States

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Hershey, Pennsylvania, 17033, United States

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Dallas, Texas, 75231, United States

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Buenos Aires, B1629AHJ, Argentina

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Salta, 4400, Argentina

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Campbelltown, New South Wales, 2560, Australia

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Graz, 8036, Austria

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Vienna, 1090, Austria

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Salvador, Estado de Bahia, 41950-640, Brazil

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Ribeirão Preto, 14048-900, Brazil

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Santo André, 09060-870, Brazil

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São Paulo, 05403-000, Brazil

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Sofia, 1431, Bulgaria

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Sofia, 1680, Bulgaria

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Edmonton, Alberta, T6G 1Z1, Canada

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Montreal, Quebec, Canada

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Brno, 602 00, Czechia

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Grenoble, 38043, France

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Paris, 75571, France

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Berlin, 12203, Germany

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Frankfurt am Main, 60590, Germany

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Frankfurt am Main, 60596, Germany

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Lübeck, 23538, Germany

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Hong Kong, Hong Kong

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Budapest, 1088, Hungary

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Ashkelon, 78278, Israel

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Catania, 95124, Italy

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Milan, 20097, Italy

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Milan, 20138, Italy

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Naples, 80131, Italy

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Padua, 35128, Italy

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Palermo, 90146, Italy

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Roma, 00133, Italy

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Hiroshima, 730-8518, Japan

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Kanagawa, 216-8511, Japan

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Osaka, 569-8686, Japan

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Tokyo, 113-8431, Japan

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Tokyo, 133-8431, Japan

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Amsterdam, 1005 AZ, Netherlands

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Krakow, 31-503, Poland

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San Juan, 918, Puerto Rico

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San Juan, 927, Puerto Rico

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Riyadh, 11471, Saudi Arabia

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Cape Town, 7700, South Africa

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Daegu, 41944, South Korea

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Seoul, 03080, South Korea

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Barcelona, 08035, Spain

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Barcelona, 08907, Spain

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Madrid, 28007, Spain

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Lund, 22185, Sweden

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Ankara, 06230, Turkey (Türkiye)

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Istanbul, 34093, Turkey (Türkiye)

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London, E1 2ES, United Kingdom

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MeSH Terms

Conditions

Angioedemas, Hereditary; Hereditary Angioedema Types I and II; Hereditary Angioedema Type III

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Study Officials

• Study Director

  Pharvaris Netherlands B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2022
• First Posted: May 31, 2022
• Study Start: December 28, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

PR (2); GB (1); KR (2); SA (1); IT (7); FR (2); PL (1); HK (1); AU (1); BU (2); HU (1); CA (2); JP (5); CZ (1); IL (1); NL (1); US (13); ZA (1); ES (3); TU (2); AR (2); SE (1); DE (4); BR (4)