Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II (HAE CHAPTER-1)

A Phase II, Double-blind, Placebo-controlled, Randomized, Dose-ranging, Parallel Group Study to Evaluate the Safety and Efficacy of PHA-022121 Administered Orally for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Due to C1-Inhibitor Deficiency (Type I or Type II)

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.

Study Overview

• Status: Active, not recruiting
• 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
• Intervention / Treatment: Drug: Placebo; Drug: Deucrictibant low dose; Drug: Deucrictibant high dose

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pharvaris Clinical Team; Phone Number: +31 (71) 203-6410; Email: clinicaltrials@pharvaris.com

Study Locations

• Austria
  • Wien, Austria, A-1090
    • Study Site
• Bulgaria
  • Sofia, Bulgaria, 1680
    • Study Site
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 1E4
      • Study Site
  • Quebec
    • Montréal, Quebec, Canada, H2W 1R7
      • Study Site
• Germany
  • Berlin, Germany, 10117
    • Study Site
  • Frankfurt, Germany, 60323
    • Study Site
• Ireland
  • Dublin, Ireland, D08NHY1
    • Study Site
• Italy
  • Milan, Italy, 20157
    • Study Site
  • Palermo, Italy, 0146
    • Study Site
  • PD
    • Padua, PD, Italy, 35128
      • Study Site
• Poland
  • Kraków, Poland
    • Study Site
• United Kingdom
  • England
    • Brighton, England, United Kingdom, BN2 1ES
      • Study Site
    • Bristol, England, United Kingdom, BS10 5NB
      • Study Site
    • Cambridge, England, United Kingdom, CB2 0QQ
      • Study Site
    • London, England, United Kingdom, E1 1FR
      • Study Site
    • Southampton, England, United Kingdom, SO16 6YD
      • Study Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Study Site
  • Arizona
    • Paradise Valley, Arizona, United States, 85253
      • Study Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part 1: Placebo; BID placebo	Drug: Placebo; Matching placebo capsules for oral use
Experimental: Part 1: Low dose; BID low dose of deucrictibant	Drug: Deucrictibant low dose; Deucrictibant softgel capsules for oral use (PHVS416)
Experimental: Part 1: High dose; BID high dose of deucrictibant	Drug: Deucrictibant high dose; Deucrictibant softgel capsules for oral use (PHVS416)
Experimental: Part 2: Open-label; BID high dose of deucrictibant	Drug: Deucrictibant high dose; Deucrictibant softgel capsules for oral use (PHVS416)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of investigator-confirmed HAE attacks	Day 0 to Day 84

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of investigator-confirmed moderate or severe HAE attacks during the treatment period	Day 0 to Day 84
Number of investigator-confirmed HAE attacks requiring acute treatment during the treatment period	Day 0 to Day 84
Number of patients achieving reduction in attack rate during the treatment period relative to baseline	Day 0 to Day 84
Number of patients that are attack-free during the treatment period	Day 0 to Day 84
Number and proportion of days with angioedema symptoms during the treatment period	Day 0 to Day 84
Time to first investigator-confirmed HAE attack in the treatment period	Day 0 to Day 84
Number of investigator-confirmed HAE attacks resulting in a visit to the emergency department or an admission to hospital	Day 0 to Day 84
Number of investigator-confirmed angioedema attacks during the treatment period in Part 2.	Day 84 to Day 938
Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period in Part 2.	Day 84 to Day 938
Number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period in Part 2.	Day 84 to Day 938
Incidence of HAE attacks during the treatment period in Part 2 (attack rate trend over time).	Day 84 to Day 938
Number and proportion of days with angioedema symptoms during the treatment period in Part 2.	Day 84 to Day 938

Collaborators and Investigators

• Sponsor: Pharvaris Netherlands B.V.
• Investigators: Principal Investigator: Marc Riedl, MD, UC San Diego, La Jolla, California, United States; Principal Investigator: Emel Aygören-Pürsün, MD, University Hospital Frankfurt - Goethe University, Frankfurt, Germany

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Actual): October 2, 2023
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Prophylaxis; HAE; HAE Type I; HAE Type II; Oral Treatment; PHVS416; PHA121; Bradykinin B2 Receptor Antagonist; Deucrictibant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II
• Other Study ID Numbers: PHA022121-C301; 2021-000227-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No