Study of Oral Deucrictibant Extended-Release Tablet for Prophylaxis Against Angioedema Attacks in Adolescents and Adults With HAE (CHAPTER-3)

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Orally Administered Deucrictibant Extended-Release Tablet for Prophylaxis Against Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of once-daily orally administered deucrictibant extended-release tablet compared to placebo for prophylaxis to prevent angioedema attacks in participants aged ≥ 12 years with hereditary angioedema.

Study Overview

• Status: Active, not recruiting
• Conditions: Hereditary Angioedema (HAE)
• Intervention / Treatment: Drug: Placebo; Drug: Deucrictibant

Detailed Description

The study consists of a Screening Period during which eligibility is confirmed, a Treatment Period of 24 weeks, and a Follow-up Period of maximum 4 weeks or subjects may roll over into the open-label study PHA022121-C307 (CHAPTER-4). During the Treatment period participants will receive blinded study drug (deucrictibant or placebo randomized in a 2:1 ratio). Participants will undergo regular efficacy and safety assessments, complete an electronic diary daily, and also complete questionnaires at predefined timepoints during the study.

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Corrientes, Argentina
    • Study Site
  • San Martín, Argentina
    • Study Site
• Brazil
  • Santo André, Brazil
    • Study Site
• Bulgaria
  • Sofia, Bulgaria, 1431
    • Study Site
  • Sofia, Bulgaria, 1680
    • Study Site
• Canada
  • Edmonton, Canada
    • Study Site
  • Ottawa, Canada
    • Study Site
• France
  • Grenoble, France
    • Study Site
  • Lille, France, 59037
    • Study Site
• Germany
  • Berlin, Germany
    • Study Site
  • Frankfurt, Germany
    • Study Site
  • Hanover, Germany
    • Study Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Study Site
• Hungary
  • Budapest, Hungary
    • Study Site
• Ireland
  • Dublin, Ireland
    • Study Site
• Italy
  • Milan, Italy, 20062
    • Study Site
  • Padua, Italy
    • Study Site
• Japan
  • Kawasaki, Japan
    • Study Site
  • Tokyo, Japan, 113-0033
    • Study Site
  • Tokyo, Japan, 1130033
    • Study Site
• New Zealand
  • Auckland, New Zealand
    • Study Site
• Poland
  • Krakow, Poland
    • Study Site
• Puerto Rico
  • San Juan, Puerto Rico
    • Study Site
• Romania
  • Sângeorgiu de Mureş, Romania
    • Study Site
• Singapore
  • Singapore, Singapore
    • Study Site
• Slovakia
  • Martin, Slovakia
    • Study Site
• South Africa
  • Cape Town, South Africa
    • Study Site
• South Korea
  • Daegu, South Korea
    • Study Site
  • Seoul, South Korea, 06351
    • Study Site
  • Seoul, South Korea
    • Study Site
  • Suwon, South Korea
    • Study Site
• Spain
  • Barcelona, Spain, 08907
    • Study Site
  • Barcelona, Spain, 08013
    • Study Site
  • Seville, Spain
    • Study Site
• Switzerland
  • Basel, Switzerland
    • Study Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye)
    • Study Site
  • Istanbul, Turkey (Türkiye)
    • Study Site
  • Izmir, Turkey (Türkiye)
    • Study Site
• United Kingdom
  • Birmingham, United Kingdom, B18 7QH
    • Study Site
  • Birmingham, United Kingdom, B9 5SS
    • Study Site
  • Bristol, United Kingdom, BS10 5NB
    • Study Site
  • Cambridge, United Kingdom, CB2 0QQ
    • Study Site
  • Frimley, United Kingdom, GU16 7UJ
    • Study Site
  • Leeds, United Kingdom, LS9 7TF
    • Study Site
  • London, United Kingdom, NW3 2QG
    • Study Site
  • Oxford, United Kingdom
    • Study Site
  • Plymouth, United Kingdom, PL6 5FP
    • Study Site
  • Southampton, United Kingdom
    • Study Site
  • Stoke, United Kingdom
    • Study Site
  • England
    • London, England, United Kingdom, E1 1FR
      • Study Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Study Site
  • California
    • San Diego, California, United States, 92122
      • Study Site
    • Santa Monica, California, United States, 90404
      • Study Site
    • Walnut Creek, California, United States, 94598
      • Study Site
  • Maryland
    • Chevy Chase, Maryland, United States, 20915
      • Study Site
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of written informed consent/assent.
2. Male or female, aged ≥12 years at the time of providing written informed consent/assent.
3. Diagnosis of hereditary angioedema (HAE)
4. History of at least 3 HAE attacks within the 3 consecutive months prior to Screening Visit
5. Predefined number of attacks during the Screening Period
6. Reliable access and ability to use standard of care on-demand treatments to effectively manage acute HAE attacks.
7. Willing and able to adhere to all protocol requirements, including eDiary and ePRO data recording.
8. Female participants of childbearing potential must agree to the protocol specified pregnancy testing and contraception methods.

Exclusion Criteria:

1. Any diagnosis of angioedema other than HAE
2. Participation in a clinical study with any other investigational drug within the last 30 days or within 5 half-lives of the investigational drug at Screening (whichever is longer)
3. Has received prior prophylactic treatment with deucrictibant
4. Exposure to ACE inhibitors or any estrogen-containing medications with systemic absorption within 4 weeks of Screening
5. Prior gene therapy for any indication at any time
6. Use of prophylactic treatment for HAE within 2 weeks of Screening for C1INH, oral kallikrein inhibitors, or anti-fibrinolytics; within 4 weeks of Screening for attenuated androgens; within 5 half-lives of Screening for monoclonal antibodies, or within 7 days of Screening for short-term prophylaxis
7. Any females who are pregnant, plan to become pregnant, or are currently breast-feeding
8. Abnormal hepatic function
9. Moderate or severe renal impairment
10. Any clinically significant comorbidity or systemic dysfunction that would interfere with the participant's safety or ability to participate in the study.
11. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse
12. Use of medications that are moderate and strong inhibitors or strong inducers of CYP3A4 within the last 30 days or within 5 half-lives (whichever is longer) of the time of randomization
13. Known hypersensitivity to deucrictibant or any of the excipients of the study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; Deucrictibant 40mg extended-release tablet by mouth once daily	Drug: Deucrictibant; Deucrictibant 40mg extended-release tablet for once daily oral use
Experimental: Placebo; Placebo 1 tablet by mouth once daily	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time-normalized (per 4 weeks) number of Investigator-confirmed HAE attacks during the 24-week Treatment Period	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-normalized number of Investigator-confirmed HAE attacks treated with on-demand medication during the 24-week Treatment Period		24 weeks
Time-normalized number of Investigator-confirmed moderate or severe HAE attacks during the 24-week Treatment Period		24 weeks
Time-normalized number of Investigator-confirmed severe HAE attacks during the 24-week Treatment Period		24 weeks
Proportion of participants achieving ≥50% reduction in HAE attack rate relative to baseline during the 24-week Treatment Period		24 weeks
Proportion of participants achieving ≥70% reduction in HAE attack rate relative to baseline during the 24-week Treatment Period		24 weeks
Proportion of participants achieving ≥90% reduction in HAE attack rate relative to baseline during the 24-week Treatment Period		24 weeks
Proportion of participants that are HAE attack-free during the 24-week Treatment Period		24 weeks
Proportion of time without angioedema symptoms during the 24-week Treatment Period		24 weeks
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation		Up to 38 weeks
Pharmacokinetics [PK]: Deucrictibant plasma concentration time profiles		24 weeks
Patient reported outcome: Angioedema Quality of Life (AE-QoL) questionnaire	The AE-QoL is a short 17-item questionnaire designed to retrospectively assess HRQoL, with a recall period of 4 weeks. Its results can be displayed as a total score or as 4 domain scores. The scores range from 0 to 100, after linear transformation of raw values, with higher scores indicating higher HRQoL impairment.	24 weeks
Patient reported outcome: Patient Global Assessment of Change (PGA-Change)	PGA-Change assesses on a 5-point scale how the participant's QoL has been impacted by HAE since start taking the study drug	24 weeks
Patient reported outcome: Angioedema Control Test 4-week version (AECT-4wk)	AECT-4wk measures disease control retrospectively, it comprises 4 questions over a 4-week recall period. Scores for the responses in the AECT range from 0 to 16, with higher scores indicating better disease control (≤ 9 poorly controlled; ≥ 10 well controlled)	24 weeks
Patient reported outcome: Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP)	WPAI-SHP is a questionnaire assessing how a health condition impacts a person's ability to work and do regular activities and it includes 4 domains. Scores indicate the percentage of time the patient missed work or was less productive owing to HAE-related complications.	Up to 34 weeks
Patient reported outcome: Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9)	TSQM-9 is a 9-item questionnaire evaluating patient treatment satisfaction and it includes 3 domains. Scoring is by domain and each domain score is computed by summing the individual TSQM items in each domain and then transforming the composite score into a value ranging from 0 to 100, with higher scores indicating higher satisfaction.	Up to 34 weeks

Collaborators and Investigators

• Sponsor: Pharvaris Netherlands B.V.
• Investigators: Study Director: Study Director, Pharvaris, Pharvaris Netherlands B.V.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: October 24, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Actual): November 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Prophylaxis; HAE; Oral Treatment; Bradykinin B2 Receptor Antagonists; PHA121; Deucrictibant; PHVS719
• Additional Relevant MeSH Terms: Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immunologic Deficiency Syndromes; Skin Diseases; Urticaria; Skin Diseases, Vascular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Angioedema; Angioedemas, Hereditary; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: PHA022121-C305

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No