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Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema (RAPIDe-1)

Primary Purpose

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

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

About this trial

This is an interventional treatment trial for Hereditary Angioedema focused on measuring HAE, HAE Type I, HAE Type II, Oral Treatment, Bradykinin B2 Receptor Antagonists, PHVS416, PHA121, PHA-022121, Deucrictibant

Eligibility Criteria

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

Key Inclusion Criteria:

  1. Signed and dated informed consent form
  2. Diagnosis of HAE type I or II
  3. Documented history of HAE attacks: at least three in the last 4 months, or at least two in the last 2 months prior to screening
  4. Reliable access and experience to use standard of care acute attack medications

Key Exclusion Criteria:

  1. Pregnancy or breast-feeding
  2. Clinically significant abnormal electrocardiogram
  3. Any other systemic disease or significant disease or disorder that would interfere with the patient's safety or ability to participate in the study
  4. Use of C1-esterase inhibitor, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy within a defined period prior to enrollment
  5. Positive serology for HIV or active infection with hepatitis B virus or hepatitis C virus
  6. Abnormal hepatic function
  7. Abnormal renal function
  8. History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
  9. History of documented severe hypersensitivity to any medicinal product
  10. 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 Type

Other

Other

Other

Arm Label

Low dose/placebo

Medium dose/placebo

High dose/placebo

Arm Description

Single low dose of deucrictibant or placebo

Single medium dose of deucrictibant or placebo

Single high dose of deucrictibant or placebo

Outcomes

Primary Outcome Measures

Change of the 3-symptom composite visual analogue scale (VAS-3) score from pre-treatment to 4 hours post-treatment
VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.

Secondary Outcome Measures

Time to onset of symptom relief by visual analogue scale (VAS-3) score
VAS-3 scores range between 0 and 100. Symptom relief is defined as a 50% or higher reduction of the VAS-3 score from the pre-treatment value.
Proportion of study drug treated attacks requiring HAE rescue medication
Qualifying attacks treated with study drug may use approved rescue medication if no symptom relief within 4 h has been experienced.
Time to onset of almost complete and complete symptom relief by visual analogue scale (VAS-3)
VAS scores range between 0 and 100. Almost complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 having a value < 10. Complete symptom relief is defined as all 3 individual VAS scores are of the VAS-3 having a value of 0.
Mean symptom complex severity (MSCS) score
MSCS scores range between 0 and 3. A higher score means a worse outcome.
Treatment outcome score (TOS)
TOS scores range between -100 and 100. A positive score indicates improvement, a score of 0 indicates no change, and a negative score indicates worsening compared to pre-treatment.
Treatment satisfaction questionnaire for medication (TSQM) scores
TSQM scores range from 0 to 100. A higher score means a better outcome.
Treatment-emergent adverse events (TEAEs)
Treatment-related adverse events (AEs)
Treatment-emergent serious adverse events (TESAEs)

Full Information

First Posted
October 26, 2020
Last Updated
June 19, 2023
Sponsor
Pharvaris Netherlands B.V.
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1. Study Identification

Unique Protocol Identification Number
NCT04618211
Brief Title
Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema
Acronym
RAPIDe-1
Official Title
A Phase II, Double-blind, Placebo-controlled, Randomized, Cross-over, Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema Due to C1-inhibitor Deficiency Type I and II
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
February 3, 2021 (Actual)
Primary Completion Date
September 23, 2022 (Actual)
Study Completion Date
March 1, 2023 (Actual)

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 efficacy of orally administered deucrictibant for the acute treatment of attacks in patients with hereditary angioedema (HAE). Eligible subjects are randomized to one of three single doses of deucrictibant and placebo. The study will compare symptom relief (skin pain, skin swelling, abdominal pain) during HAE attacks and safety of each dose of deucrictibant with placebo.
Detailed Description
In Part I of the study, patients in non-attack state receive the assigned active single dose of deucrictibant at the study center to assess pharmacokinetics (the way the body absorbs, distributes, and gets rid of the drug) and safety. In Part II of the study, patients self-administer blinded study drug at home to treat three HAE attacks with deucrictibant or placebo (cross-over).

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 Antagonists, PHVS416, PHA121, PHA-022121, Deucrictibant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low dose/placebo
Arm Type
Other
Arm Description
Single low dose of deucrictibant or placebo
Arm Title
Medium dose/placebo
Arm Type
Other
Arm Description
Single medium dose of deucrictibant or placebo
Arm Title
High dose/placebo
Arm Type
Other
Arm Description
Single high dose of deucrictibant or placebo
Intervention Type
Drug
Intervention Name(s)
Deucrictibant
Other Intervention Name(s)
PHA-022121, PHA121, PHVS416
Intervention Description
deucrictibant soft capsules for oral use
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo capsules for oral use
Primary Outcome Measure Information:
Title
Change of the 3-symptom composite visual analogue scale (VAS-3) score from pre-treatment to 4 hours post-treatment
Description
VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.
Time Frame
Pre-treatment and 4 hours post-treatment
Secondary Outcome Measure Information:
Title
Time to onset of symptom relief by visual analogue scale (VAS-3) score
Description
VAS-3 scores range between 0 and 100. Symptom relief is defined as a 50% or higher reduction of the VAS-3 score from the pre-treatment value.
Time Frame
Assessed from pre-treatment to 48 hours post-treatment
Title
Proportion of study drug treated attacks requiring HAE rescue medication
Description
Qualifying attacks treated with study drug may use approved rescue medication if no symptom relief within 4 h has been experienced.
Time Frame
Assessed at 4 hours post-study drug treatment
Title
Time to onset of almost complete and complete symptom relief by visual analogue scale (VAS-3)
Description
VAS scores range between 0 and 100. Almost complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 having a value < 10. Complete symptom relief is defined as all 3 individual VAS scores are of the VAS-3 having a value of 0.
Time Frame
Assessed from pre-treatment to 48 hours post-treatment
Title
Mean symptom complex severity (MSCS) score
Description
MSCS scores range between 0 and 3. A higher score means a worse outcome.
Time Frame
4 hours post-treatment
Title
Treatment outcome score (TOS)
Description
TOS scores range between -100 and 100. A positive score indicates improvement, a score of 0 indicates no change, and a negative score indicates worsening compared to pre-treatment.
Time Frame
Pre-treatment and 4 hours post-treatment
Title
Treatment satisfaction questionnaire for medication (TSQM) scores
Description
TSQM scores range from 0 to 100. A higher score means a better outcome.
Time Frame
48 hours post-treatment
Title
Treatment-emergent adverse events (TEAEs)
Time Frame
From post-dose non-attack visit through study completion, approximately 26 weeks
Title
Treatment-related adverse events (AEs)
Time Frame
From post-dose non-attack visit through study completion, approximately 26 weeks
Title
Treatment-emergent serious adverse events (TESAEs)
Time Frame
From post-dose non-attack visit through study completion, approximately 26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Signed and dated informed consent form Diagnosis of HAE type I or II Documented history of HAE attacks: at least three in the last 4 months, or at least two in the last 2 months prior to screening Reliable access and experience to use standard of care acute attack medications Key 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 enrollment Positive serology for HIV or active infection with hepatitis B virus or hepatitis C virus Abnormal hepatic function Abnormal renal function History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse History of documented severe hypersensitivity to any medicinal product Participation in any other investigational drug study within defined period
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcus Maurer, Prof MD
Organizational Affiliation
Charite University, Berlin, 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
San Diego
State/Province
California
ZIP/Postal Code
92122
Country
United States
Facility Name
Study site
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Study site
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Study site
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
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
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Study site
City
Sofia
Country
Bulgaria
Facility Name
Study site
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
Study site
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Study site
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Study site
City
Montréal
State/Province
Quebec
Country
Canada
Facility Name
Study site
City
Québec City
State/Province
Quebec
Country
Canada
Facility Name
Study site
City
Brno
Country
Czechia
Facility Name
Study site
City
Hradec Králové
Country
Czechia
Facility Name
Study site
City
Grenoble
Country
France
Facility Name
Study site
City
Montpellier
Country
France
Facility Name
Study site
City
Paris
Country
France
Facility Name
Study site
City
Berlin
Country
Germany
Facility Name
Study site
City
Dresden
Country
Germany
Facility Name
Study site
City
Frankfurt
Country
Germany
Facility Name
Study site
City
Mainz
Country
Germany
Facility Name
Study site
City
Ulm
Country
Germany
Facility Name
Study site
City
Budapest
Country
Hungary
Facility Name
Study site
City
Ashkelon
Country
Israel
Facility Name
Study site
City
Haifa
Country
Israel
Facility Name
Study site
City
Tel Aviv
Country
Israel
Facility Name
Study site
City
Monserrato
Country
Italy
Facility Name
Study site
City
Naples
Country
Italy
Facility Name
Study site
City
Amsterdam
Country
Netherlands
Facility Name
Study site
City
Kraków
Country
Poland
Facility Name
Study site
City
Barcelona
Country
Spain
Facility Name
Study site
City
Madrid
Country
Spain
Facility Name
Study site
City
Brighton
Country
United Kingdom
Facility Name
Study site
City
London
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 Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema

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