Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II

NCT05047185 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: PHA022121-C3012021-000227-13
• Study Type: interventional
• Target: 34
• Locations: 9 countries
• Sites: 19

Brief Summary

This study evaluates the safety and efficacy of PHA-022121 administered orally for prophylaxis against angioedema attacks in patients with hereditary angioedema (HAE). The study consists of 2 parts, with patients completing participation in Part 1 prior to initiation of treatment in Part 2. Part 1 of the study has 3 parallel arms and approximately 30 patients will be equally randomized to one of two dose regimens of PHA-022121 or matching placebo. Patients will continue to the single open-label arm in Part 2 of the study after completion of Part 1. The screening period is up to 8 weeks and the treatment periods are 12 weeks (Part 1) and 30 months (Part 2) in duration.

Conditions

Hereditary Angioedema; Hereditary Angioedema Type I; Hereditary Angioedema Type 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; Hereditary Angioedema Types I and II

Keywords

HAE; HAE Type I; HAE Type II; Oral Treatment; Bradykinin B2 Receptor Antagonist; PHVS416; PHA121; Prophylaxis; Deucrictibant

Outcome Measures

Primary Outcomes (1)

• Number of Investigator-confirmed Hereditary Angioedema (HAE) Attacks (Expressed as the Normalized Number of Attacks Per Month [4 Weeks] of Exposure) During the Treatment Period in Part 1

  HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily electronic patient-reported outcome (ePRO) diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28. Mean rate ratio, confidence interval (CI), and p-value were estimated using a generalized linear model with Poisson distribution, with baseline attack rate included as a factor.

  Up to Day 84

Secondary Outcomes (13)

• Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 1

  Up to Day 84

• Number of Investigator-confirmed HAE Attacks Requiring Acute Treatment During the Treatment Period in Part 1

  Up to Day 84

• Number of Participants Achieving ≥50%, ≥70% and ≥90% Reduction in Attack Rate Relative to Baseline During the Treatment Period in Part 1

  Up to Day 84

• Number of Participants Who Were Investigator-confirmed Attack-free During the Treatment Period in Part 1

  Up to Day 84

• Number of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 1

  Up to Day 84

Study Arms (4)

Part 1: Low dose

EXPERIMENTAL

BID low dose of deucrictibant

Drug: Deucrictibant low dose

Part 1: High dose

EXPERIMENTAL

BID high dose of deucrictibant

Drug: Deucrictibant high dose

Part 1: Placebo

PLACEBO COMPARATOR

BID placebo

Drug: Placebo

Part 2: Open-label

EXPERIMENTAL

BID high dose of deucrictibant

Drug: Deucrictibant high dose

Interventions

Deucrictibant low dose DRUG

Deucrictibant softgel capsules for oral use (PHVS416)

Part 1: Low dose

Deucrictibant high dose DRUG

Deucrictibant softgel capsules for oral use (PHVS416)

Part 1: High dose; Part 2: Open-label

Placebo DRUG

Matching placebo capsules for oral use

Part 1: 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 at least 3 HAE attacks within the last 3 consecutive months prior to screening, or a minimum of 2 HAE attacks during the screening period
• 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 enrolment
• Abnormal hepatic function
• Abnormal renal function
• History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
• Participation in any other investigational drug study within defined period

Sponsors & Collaborators

• Pharvaris Netherlands B.V.: lead

Study Sites (19)

Study site

Birmingham, Alabama, 35209, United States

Location

Study site

Paradise Valley, Arizona, 85253, United States

Location

Study site

St Louis, Missouri, 63141, United States

Location

Study Site

Vienna, A-1090, Austria

Location

Study site

Sofia, 1680, Bulgaria

Location

Study site

Ottawa, Ontario, K1H 1E4, Canada

Location

Study site

Montreal, Quebec, H2W 1R7, Canada

Location

Study site

Berlin, 10117, Germany

Location

Study site

Frankfurt, 60323, Germany

Location

Study site

Dublin, D08NHY1, Ireland

Location

Study site

Padua, PD, 35128, Italy

Location

Study site

Milan, 20157, Italy

Location

Study site

Palermo, 0146, Italy

Location

Study site

Krakow, Poland

Location

Study site

Brighton, England, BN2 1ES, United Kingdom

Location

Study site

Bristol, England, BS10 5NB, United Kingdom

Location

Study site

Cambridge, England, CB2 0QQ, United Kingdom

Location

Study site

London, England, E1 1FR, United Kingdom

Location

Study site

Southampton, England, SO16 6YD, United Kingdom

Location

Related Publications (1)

• Aygoren-Pursun E, Stobiecki M, Valerieva A, Cancian M, Gompels M, Grigoriadou S, Kiani-Alikhan S, Kinaciyan T, Yang WH, Anderson J, Arcoleo F, Chapdelaine H, Conlon N, Eren E, Guarino MD, Gurugama P, Magerl M, Manning ME, Tarzi MD, Wedner HJ, Zanichelli A, Crabbe R, Mulders S, Levy J, Zhu L, Knolle J, Lesage A, Lu P, Riedl MA. Oral deucrictibant for prophylaxis of hereditary angioedema attacks (CHAPTER-1): primary analysis of a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haematol. 2026 Apr;13(4):e215-e226. doi: 10.1016/S2352-3026(26)00004-9. Epub 2026 Mar 19.

  PMID: 41865746 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

Results Point of Contact

• Title: Pharvaris Netherlands B.V. - Pharvaris clinical
• Organization: Pharvaris Netherlands B.V.

clinical@pharvaris.com

+31712036410

Study Officials

• Marc Riedl, MD

  UC San Diego, La Jolla, California, United States

  PRINCIPAL INVESTIGATOR

• Emel Aygören-Pürsün, MD

  University Hospital Frankfurt - Goethe University, Frankfurt, Germany

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: September 17, 2021
• Study Start: April 19, 2022
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: August 17, 2026
• Results First Posted: August 17, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1); US (3); AU (1); DE (2); PL (1); GB (5); IT (3); CA (2); IE (1)