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)

• ClinicalTrials.gov Identifier: NCT05047185
• Recruitment Status: Active, not recruiting
• First Posted: September 17, 2021
• Last Update Posted: February 21, 2024
• Sponsor: Pharvaris Netherlands B.V.
• Information provided by (Responsible Party): Pharvaris Netherlands B.V.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
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	Drug: Deucrictibant low dose; Drug: Deucrictibant high dose; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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)
• Actual Study Start Date: April 19, 2022
• Actual Primary Completion Date: October 2, 2023
• Estimated Study Completion Date: December 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of investigator-confirmed HAE attacks [ Time Frame: Day 0 to Day 84 ]

Secondary Outcome Measures :

1. Number of investigator-confirmed moderate or severe HAE attacks during the treatment period [ Time Frame: Day 0 to Day 84 ]
2. Number of investigator-confirmed HAE attacks requiring acute treatment during the treatment period [ Time Frame: Day 0 to Day 84 ]
3. Number of patients achieving reduction in attack rate during the treatment period relative to baseline [ Time Frame: Day 0 to Day 84 ]
4. Number of patients that are attack-free during the treatment period [ Time Frame: Day 0 to Day 84 ]
5. Number and proportion of days with angioedema symptoms during the treatment period [ Time Frame: Day 0 to Day 84 ]
6. Time to first investigator-confirmed HAE attack in the treatment period [ Time Frame: Day 0 to Day 84 ]
7. Number of investigator-confirmed HAE attacks resulting in a visit to the emergency department or an admission to hospital [ Time Frame: Day 0 to Day 84 ]
8. Number of investigator-confirmed angioedema attacks during the treatment period in Part 2. [ Time Frame: Day 84 to Day 938 ]
9. Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period in Part 2. [ Time Frame: Day 84 to Day 938 ]
10. Number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period in Part 2. [ Time Frame: Day 84 to Day 938 ]
11. Incidence of HAE attacks during the treatment period in Part 2 (attack rate trend over time). [ Time Frame: Day 84 to Day 938 ]
12. Number and proportion of days with angioedema symptoms during the treatment period in Part 2. [ Time Frame: Day 84 to Day 938 ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Alabama

Study site

Birmingham, Alabama, United States, 35209

United States, Arizona

Study site

Paradise Valley, Arizona, United States, 85253

United States, Missouri

Study site

Saint Louis, Missouri, United States, 63141

Austria

Study Site

Wien, Austria, A-1090

Bulgaria

Study site

Sofia, Bulgaria, 1680

Canada, Ontario

Study site

Ottawa, Ontario, Canada, K1H 1E4

Canada, Quebec

Study site

Montréal, Quebec, Canada, H2W 1R7

Germany

Study site

Berlin, Germany, 10117

Study site

Frankfurt, Germany, 60323

Ireland

Study site

Dublin, Ireland, D08NHY1

Italy

Study site

Padua, PD, Italy, 35128

Study site

Milan, Italy, 20157

Study site

Palermo, Italy, 0146

Poland

Study site

Kraków, Poland

United Kingdom

Study site

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

Sponsors and Collaborators

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

More Information

• Responsible Party: Pharvaris Netherlands B.V.
• ClinicalTrials.gov Identifier: NCT05047185
• Other Study ID Numbers: PHA022121-C301; 2021-000227-13 ( EudraCT Number )
• First Posted: September 17, 2021
• Last Update Posted: February 21, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pharvaris Netherlands B.V.:

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

Additional relevant MeSH terms:

Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes