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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)

Primary Purpose

Hereditary Angioedema, Hereditary Angioedema Type I, Hereditary Angioedema Type II

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Deucrictibant low dose
Deucrictibant high dose
Placebo
Sponsored by
Pharvaris Netherlands B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hereditary Angioedema focused on measuring HAE, HAE Type I, HAE Type II, Oral Treatment, Bradykinin B2 Receptor Antagonist, PHVS416, PHA121, Prophylaxis, Deucrictibant

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Placebo Comparator

Experimental

Arm Label

Part 1: Low dose

Part 1: High dose

Part 1: Placebo

Part 2: Open-label

Arm Description

BID low dose of deucrictibant

BID high dose of deucrictibant

BID placebo

BID high dose of deucrictibant

Outcomes

Primary Outcome Measures

Number of investigator-confirmed HAE attacks

Secondary Outcome Measures

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

Full Information

First Posted
September 7, 2021
Last Updated
July 25, 2023
Sponsor
Pharvaris Netherlands B.V.
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1. Study Identification

Unique Protocol Identification Number
NCT05047185
Brief Title
Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II
Acronym
HAE CHAPTER-1
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)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 19, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharvaris Netherlands B.V.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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 Antagonist, PHVS416, PHA121, Prophylaxis, Deucrictibant

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Low dose
Arm Type
Experimental
Arm Description
BID low dose of deucrictibant
Arm Title
Part 1: High dose
Arm Type
Experimental
Arm Description
BID high dose of deucrictibant
Arm Title
Part 1: Placebo
Arm Type
Placebo Comparator
Arm Description
BID placebo
Arm Title
Part 2: Open-label
Arm Type
Experimental
Arm Description
BID high dose of deucrictibant
Intervention Type
Drug
Intervention Name(s)
Deucrictibant low dose
Intervention Description
Deucrictibant softgel capsules for oral use (PHVS416)
Intervention Type
Drug
Intervention Name(s)
Deucrictibant high dose
Intervention Description
Deucrictibant softgel capsules for oral use (PHVS416)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo capsules for oral use
Primary Outcome Measure Information:
Title
Number of investigator-confirmed HAE attacks
Time Frame
Day 0 to Day 84
Secondary Outcome Measure Information:
Title
Number of investigator-confirmed moderate or severe HAE attacks during the treatment period
Time Frame
Day 0 to Day 84
Title
Number of investigator-confirmed HAE attacks requiring acute treatment during the treatment period
Time Frame
Day 0 to Day 84
Title
Number of patients achieving reduction in attack rate during the treatment period relative to baseline
Time Frame
Day 0 to Day 84
Title
Number of patients that are attack-free during the treatment period
Time Frame
Day 0 to Day 84
Title
Number and proportion of days with angioedema symptoms during the treatment period
Time Frame
Day 0 to Day 84
Title
Time to first investigator-confirmed HAE attack in the treatment period
Time Frame
Day 0 to Day 84
Title
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
Title
Number of investigator-confirmed angioedema attacks during the treatment period in Part 2.
Time Frame
Day 84 to Day 938
Title
Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period in Part 2.
Time Frame
Day 84 to Day 938
Title
Number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period in Part 2.
Time Frame
Day 84 to Day 938
Title
Incidence of HAE attacks during the treatment period in Part 2 (attack rate trend over time).
Time Frame
Day 84 to Day 938
Title
Number and proportion of days with angioedema symptoms during the treatment period in Part 2.
Time Frame
Day 84 to Day 938

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Riedl, MD
Organizational Affiliation
UC San Diego, La Jolla, California, United States
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Emel Aygören-Pürsün, MD
Organizational Affiliation
University Hospital Frankfurt - Goethe University, Frankfurt, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Study site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Study site
City
Paradise Valley
State/Province
Arizona
ZIP/Postal Code
85253
Country
United States
Facility Name
Study site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Study site
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
Study Site
City
Wien
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Study site
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
Study site
City
Sofia
ZIP/Postal Code
1680
Country
Bulgaria
Facility Name
Study site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 1E4
Country
Canada
Facility Name
Study site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3B 3S6
Country
Canada
Facility Name
Study site
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2W 1R7
Country
Canada
Facility Name
Study site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Study site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Study site
City
Frankfurt
ZIP/Postal Code
60323
Country
Germany
Facility Name
Study site
City
Dublin
ZIP/Postal Code
D08NHY1
Country
Ireland
Facility Name
Study site
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Study site
City
Haifa
Country
Israel
Facility Name
Study site
City
Tel Aviv-Yafo
Country
Israel
Facility Name
Study site
City
Padua
State/Province
PD
ZIP/Postal Code
35128
Country
Italy
Facility Name
Study site
City
Milan
ZIP/Postal Code
20157
Country
Italy
Facility Name
Study site
City
Palermo
ZIP/Postal Code
0146
Country
Italy
Facility Name
Study site
City
Kraków
Country
Poland
Facility Name
Study site
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Study site
City
Birmingham
State/Province
England
ZIP/Postal Code
B18 7QH
Country
United Kingdom
Facility Name
Study site
City
Brighton
State/Province
England
ZIP/Postal Code
BN2 1ES
Country
United Kingdom
Facility Name
Study site
City
Bristol
State/Province
England
ZIP/Postal Code
BS10 5NB
Country
United Kingdom
Facility Name
Study site
City
Cambridge
State/Province
England
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
Study site
City
London
State/Province
England
ZIP/Postal Code
E1 1FR
Country
United Kingdom
Facility Name
Study site
City
Manchester
State/Province
England
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Study site
City
Southampton
State/Province
England
ZIP/Postal Code
SO16 6YD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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