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

NCT04618211 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: PHA022121-C2012020-003445-11
• Study Type: interventional
• Target: 74
• Locations: 13 countries
• Sites: 36

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.

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

Outcome Measures

Primary Outcomes (1)

• Change of the 3-symptom Composite Visual Analogue Scale (VAS-3) Score From Pre-treatment to 4 Hours Post-treatment

  The primary endpoint of the study was the change of the VAS-3 (3-symptom composite visual analogue scale) score from pre-treatment to 4 hours post-treatment. The VAS-3 was calculated as the mean of the VAS scores of the 3 major HAE symptoms: skin swelling, skin pain, and abdominal pain. The VAS scores of the 3 major HAE symptoms (skin swelling, skin pain, and abdominal pain) could range between 0 (No swelling/No pain) and 100 (Extreme swelling/Excruciating pain)

  Assessed from pre-treatment to 4 hours post-treatment

Secondary Outcomes (19)

• Time to Onset of Symptom Relief by ≥30% Reduction in Visual Analogue Scale (VAS-3) Composite Score From the Pre-treatment Score

  Assessed from pre-treatment to 48-hours post-treatment

• Time to Onset of Almost Complete or Complete Symptom Relief by Visual Analogue Scale (VAS-3)

  Assessed from pre-treatment to 48 hours post-treatment

• Time to a ≥50% Reduction in VAS-3 Composite Score From the Pre-treatment Score

  Assessed from pre-treatment to 48 hours post-treatment

• Change in the Mean Symptom Complex Severity (MSCS) Score From Pre-treatment to 4 Hours Post-treatment

  Pre-treatment and 4 hours post-treatment

• Treatment Outcome Score (TOS) at 4 Hours Post-treatment

  4 hours post-treatment

Study Arms (3)

Low dose/placebo

OTHER

Single low dose of deucrictibant or placebo

Drug: Deucrictibant; Drug: Placebo

Medium dose/placebo

OTHER

Single medium dose of deucrictibant or placebo

Drug: Deucrictibant; Drug: Placebo

High dose/placebo

OTHER

Single high dose of deucrictibant or placebo

Drug: Deucrictibant; Drug: Placebo

Interventions

Deucrictibant DRUG

deucrictibant soft capsules for oral use

Also known as: PHA-022121, PHA121, PHVS416

High dose/placebo; Low dose/placebo; Medium dose/placebo

Placebo DRUG

Matching placebo capsules for oral use

High dose/placebo; Low dose/placebo; Medium dose/placebo

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent form
• Diagnosis of HAE type I or II
• 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
• Reliable access and experience to use standard of care acute attack medications

You may not qualify if:

• 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 enrollment
• Positive serology for HIV or active infection with hepatitis B virus or hepatitis C virus
• Abnormal hepatic function
• Abnormal renal function
• History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
• History of documented severe hypersensitivity to any medicinal product
• Participation in any other investigational drug study within defined period

Sponsors & Collaborators

• Pharvaris Netherlands B.V.: lead

Study Sites (36)

Study site

Birmingham, Alabama, 35209, United States

Location

Study site

Paradise Valley, Arizona, 85253, 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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Chevy Chase, Maryland, 20815, 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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Sofia, Bulgaria

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Edmonton, Alberta, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Brno, Czechia

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Hradec Králové, Czechia

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Grenoble, France

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Montpellier, France

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Paris, France

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Berlin, Germany

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Dresden, Germany

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Frankfurt, Germany

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Mainz, Germany

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Ulm, Germany

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Budapest, Hungary

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Ashkelon, Israel

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Haifa, Israel

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Tel Aviv, Israel

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Monserrato, Italy

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Naples, Italy

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Amsterdam, Netherlands

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Krakow, Poland

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Barcelona, Spain

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Madrid, Spain

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Brighton, United Kingdom

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London, United Kingdom

Location

Related Publications (1)

• Maurer M, Stobiecki M, Valerieva A, Hakl R, Staevska MT, Bouillet L, Du-Thanh A, Kessel A, Kiani-Alikhan S, Magerl M, Reshef A, Baeza ML, Fain O, Farkas H, Greve J, Guilarte M, Jacobs JS, Li HH, Lleonart R, Manning ME, Sussman GL, Anderson J, Chapdelaine H, Cohn DM, Hagin D, Kralickova P, Ritchie B, Spadaro G, Staubach P, Tarzi MD, Yang WH, Jouvin MH, Crabbe R, van Leeuwen S, Chen H, Zhu L, Knolle J, Lesage A, Lu P, Riedl MA, Aygoren-Pursun E. Oral deucrictibant for on-demand treatment of hereditary angioedema attacks (RAPIDe-1): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haematol. 2026 Mar 19:S2352-3026(25)00341-2. doi: 10.1016/S2352-3026(25)00341-2. Online ahead of print.

  PMID: 41865747 DERIVED

MeSH Terms

Conditions

Angioedemas, Hereditary; Hereditary Angioedema Types I and II

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

Limitations and Caveats

Primary analysis is presented. For the endpoints "Time to Onset of Symptom Relief by 30% Reduction in Visual Analogue Scale (VAS-3)," "Time to almost or complete symptom relief by VAS," \& "Time to 50% reduction in VAS-3," the within participant correlation was not accounted for in the Kaplan-Meier estimation of median time and corresponding 95% confidence interval. Participant flow is reported according to randomized treatment cohort, efficacy \& safety results are according to treatment group.

Results Point of Contact

• Title: Pharvaris Clinical
• Organization: Pharvaris Netherlands B.V.

clinical@pharvaris.com

31 712036410

Study Officials

• Marcus Maurer, Prof MD

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: October 26, 2020
• First Posted: November 5, 2020
• Study Start: February 3, 2021
• Primary Completion: September 23, 2022
• Study Completion: March 1, 2023
• Last Updated: December 17, 2025
• Results First Posted: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IL (3); PL (1); CZ (2); DE (5); BU (1); IT (2); FR (3); HU (1); NL (1); ES (2); GB (2); CA (5); US (8)