Study of Oral Deucrictibant Soft Capsule for On-Demand Treatment of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema

NCT06343779 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: PHA022121-C306
• Study Type: interventional
• Target: 134
• Locations: 28 countries
• Sites: 73

Brief Summary

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-period, 2-treatment cross-over study to evaluate the efficacy and safety of orally administered deucrictibant compared to placebo for the on-demand treatment of HAE attacks, including non-severe laryngeal attacks, in participants ≥12 to ≤75 years of age with HAE type 1, type 2, or type 3, a proportion of whom are using long-term prophylactic medication for HAE.

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 3; Hereditary Angioedema Type III

Keywords

HAE; HAE Type I; HAE Type II; Oral Treatment; Bradykinin B2 Receptor Antagonists; PHVS416; PHA121; On-Demand; Deucrictibant; Pharvaris; HAE Type III

Outcome Measures

Primary Outcomes (1)

• 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.

  The PGI-C (7-point scale) is used to evaluate the change in the HAE attack symptoms as compared to pre-treatment.

  Pre-treatment to 12 hours post-treatment.

Secondary Outcomes (11)

• Proportion of study drug-treated attacks achieving PGI-C rating of at least "a little better" at 4 hours post-treatment.

  Pre-treatment to 4 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.

  Pre-treatment to 12 hours post-treatment.

• Time to substantial symptom relief by Patient Global Impression of Severity (PGI-S).

  Pre-treatment to 12 hours post-treatment.

• Time to complete symptom resolution, defined as achieving PGI-S rating of "none" within 48 hours post-treatment.

  Pre-treatment to 48 hours post-treatment.

• Time to End of Progression (EoP) in attack symptoms within 12 hours.

  Pre-treatment to 12 hours post-treatment.

Study Arms (2)

Arm 1

EXPERIMENTAL

Deucrictibant administered for first HAE attack, placebo administered for second HAE attack.

Drug: Deucrictibant, Placebo

Arm 2

EXPERIMENTAL

Placebo administered for first HAE attack, deucrictibant administered for second HAE attack.

Drug: Deucrictibant, Placebo

Interventions

Deucrictibant, Placebo DRUG

Deucrictibant Soft Capsules for Oral Use

Arm 1; Arm 2

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent/assent.
• Male or female, aged ≥12 to ≤75 years at the time of providing written informed consent/assent.
• Diagnosis of HAE-1/2/3.
• History of at least 2 HAE attacks in the last 3 months before screening.
• Experience with using standard-of-care treatment to effectively manage on-demand treatment for HAE attacks.
• Participants on long-term prophylactic therapy with plasma-derived C1-INH (danazol, anti-fibrinolytics, berotralstat, or lanadelumab) must be on a stable dose and regimen and intend to remain on the same dose for 6 months before screening and the duration of the study. OR, Participant has stopped using plasma-derived C1-INH (danazol, anti-fibrinolytics, berotralstat) at least 2 weeks or lanadelumab at least 10 weeks before screening.
• Capable of recording, without assistance, electronic HAE diary and ePRO data using an electronic device.
• For adolescent participants aged ≥12 and \<18 years of age: body weight ≥40 kg.
• Female participants of childbearing potential must agree to the protocol specified pregnancy testing and contraception methods.

You may not qualify if:

• Any female who is pregnant, plans to become pregnant, or is breastfeeding.
• Any diagnosis of angioedema other than HAE.
• Any clinically significant comorbidity or systemic dysfunction that would interfere with the participant's safety or ability to participate in the study.
• Use of attenuated androgens for short-term prophylaxis within 2 weeks before screening.
• Abnormal hepatic function.
• Abnormal renal function (eGFR \<60 ml/min/1.73 m2).
• History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse.
• Has received prior on-demand HAE treatment with deucrictibant.
• Currently participating in any other investigational drug study or receiving other investigational treatment within the last 30 days, or within 5 half-lives (whichever is longer) of the time of randomization.
• Prior gene therapy for any indication at any time.
• Use of concomitant medications with systemic absorption that are strong inhibitors of CYP3A4 or strong inducers of CYP3A4 within the last 30 days, or within 5 half-lives (whichever is longer) of the time of randomization.
• Known hypersensitivity to study drug or any of the excipients of study drug.

Sponsors & Collaborators

• Pharvaris Netherlands B.V.: lead

Study Sites (76)

Study Site

Birmingham, Alabama, 35209, United States

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Paradise Valley, 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, 80907-6231, 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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Box Hill, 3128, Australia

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Graz, 8036, Austria

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Linz, 4021, Austria

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Vienna, 1090, Austria

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Paraná, 80810-100, Brazil

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Ribeirão Preto, 14048-900, Brazil

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Salvador, 41950-640, 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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Bogotá, 00, Colombia

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Bogotá, 111221, Colombia

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Bogotá, 111711, Colombia

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Medellín, 050021, Colombia

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Brno, 602 00, Czechia

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Lille, 59037, 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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Dublin, D08 A978, Ireland

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Catania, 95124, Italy

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Milan, 20138, Italy

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Milan, 20097, 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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Chiba, 260-8677, Japan

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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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Amsterdam, 1105 AZ, Netherlands

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Skopje, 1000, North Macedonia

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Krakow, 31-503, Poland

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San Juan, 00918, Puerto Rico

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San Juan, 00927, Puerto Rico

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Sângeorgiu de Mureş, 547530, Romania

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Riyadh, 11471, Saudi Arabia

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Singapore, 308433, Singapore

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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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Lund, 22185, Sweden

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Ankara, 06203, Turkey (Türkiye)

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Istanbul, 34093, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Bristol, BS10 5NB, United Kingdom

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Camberley, GU16 7UJ, United Kingdom

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Cambridge, CB2 0QQ, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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London, E1 2ES, United Kingdom

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Plymouth, PL6 8DH, 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

  Pharvaris Netherlands B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: April 3, 2024
• Study Start: February 26, 2024
• Primary Completion: October 17, 2025
• Study Completion: October 17, 2025
• Last Updated: November 21, 2025

Record last verified: 2025-11

Locations

ZA (1); CA (1); GB (6); FR (2); HK (1); IT (6); TU (3); SE (1); BU (2); AR (2); JP (5); BR (5); US (13); HU (1); SA (1); RO (1); ES (2); AU (2); PR (2); IE (1); PL (1); DE (4); CZ (1); CO (4); KR (2); SG (1); NL (1); NO (1)