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Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema (RAPIDe-2)

Primary Purpose

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

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
deucrictibant low dose
deucrictibant medium dose
deucrictibant high dose
deucrictibant selected dose
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, On-Demand, PHA121, PHVS416, PHA-022121, Deucrictibant

Eligibility Criteria

18 Years - undefined (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. must have received at least 1 dose of study drug (including the non-attack visit) in Study PHA022121-C201.

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 enrolment
  5. History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
  6. Discontinued from Study PHA022121-C201 after enrollment for any study drug-related safety reason.
  7. Use of concomitant medications that are potent CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole, ritonavir, grapefruit) or potent CYP3A4 inducers (e.g., phenytoin, rifampicin, St. John's Wort).
  8. Participation in any other investigational drug study within defined period

Sites / Locations

  • Study site
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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Part A: Low dose

Part A: Medium dose

Part A: High dose

Part B: Selected dose

Arm Description

Single low dose of deucrictibant

Single medium dose of deucrictibant

Single high dose of deucrictibant

Single dose of deucrictibant

Outcomes

Primary Outcome Measures

Treatment-emergent Adverse Events (TEAEs), treatment-related TEAEs, treatment-emergent serious adverse events (TESAEs), and treatment-related TESAEs
Heart Rate
Descriptive in nature, no formal statistical hypothesis testing will be performed.
Blood pressure
Systolic and diastolic blood pressure will be measured. Descriptive in nature, no formal statistical hypothesis testing will be performed.
Body temperature
Descriptive in nature, no formal statistical hypothesis testing will be performed.

Secondary Outcome Measures

Time to onset of symptom relief (TOSR) assessed by the 3- or 5-symptom visual analog scale score (VAS-3 or VAS-5)
VAS-3 (non-laryngeal attacks) and VAS-5 (laryngeal attacks) scores range between 0 and 100. Symptom relief is defined as a 50% or higher reduction of the VAS-3 or VAS-5 score from the pre-treatment value.
Time to almost complete or complete symptom relief (TACSR and TCSR) assessed by VAS-3 or VAS-5
VAS scores range between 0 and 100. Almost complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 or VAS-5 having a value < 10. Complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 or VAS-5 having a value of 0.
Time to symptom improvement based on patient global impression of severity (PGI-S)
PGI-S evaluates the severity of attack symptoms with a 5-point response scale.
Time to symptom improvement based on patient global impression of change (PGI-C)
PGI-C evaluates the change in the attack symptoms over time with a 7-point response scale.
Change of VAS-3 score and individual VAS score from pre-treatment to 4 h post-treatment for non-laryngeal attacks
VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.
Change in 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.
Proportion of PHA-022121-treated attacks requiring a second dose of PHA-022121
Treatment satisfaction questionnaire for medication (TSQM) scores
TSQM scores range from 0 to 100. A higher score means a better outcome.

Full Information

First Posted
April 28, 2022
Last Updated
May 10, 2023
Sponsor
Pharvaris Netherlands B.V.
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1. Study Identification

Unique Protocol Identification Number
NCT05396105
Brief Title
Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema
Acronym
RAPIDe-2
Official Title
A Phase II/III, Extension Study of Orally Administered PHA-022121 for Acute Treatment of 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
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 28, 2022 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (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 long-term on-demand treatment with orally administered deucrictibant for acute hereditary angioedema (HAE) attacks, including laryngeal attacks, in patients with HAE due to C1-esterase inhibitor (C1-INH) deficiency (type I/II). The study will enroll patients from Study PHA022121-C201 (NCT04618211) who elect to participate in this extension study and meet the eligibility requirements.
Detailed Description
In Part A of the study, the double-blind treatment assignment from Study PHA022121-C201 will be maintained. The treatment in Part A will consist of 3 soft capsules per administered dose as in Study PHA022121-C201. In Part B of the study, the selected dose and formulation of deucrictibant will be administered. The to-be-marketed deucrictibant formulation will be one single soft capsule at the strength proposed for marketing, based on the unblinding and evaluation of clinical data from Study PHA022121-C201. The duration of the treatment period (Part A plus Part B) is dependent upon the time of patient enrollment. The study is planned to continue until the availability of commercial supply, or another means of continued treatment can be provided.

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 [C1-INH] Deficiency, C1 Esterase Inhibitor Deficiency, C1 Esterase Inhibitor, Deficiency of, C1 Inhibitor Deficiency
Keywords
HAE, HAE Type I, HAE Type II, Oral Treatment, Bradykinin B2 Receptor Antagonists, On-Demand, PHA121, PHVS416, PHA-022121, Deucrictibant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Non-Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part A: Low dose
Arm Type
Experimental
Arm Description
Single low dose of deucrictibant
Arm Title
Part A: Medium dose
Arm Type
Experimental
Arm Description
Single medium dose of deucrictibant
Arm Title
Part A: High dose
Arm Type
Experimental
Arm Description
Single high dose of deucrictibant
Arm Title
Part B: Selected dose
Arm Type
Experimental
Arm Description
Single dose of deucrictibant
Intervention Type
Drug
Intervention Name(s)
deucrictibant low dose
Other Intervention Name(s)
PHVS416, PHA121, PHA-022121
Intervention Description
deucrictibant soft capsules for oral use
Intervention Type
Drug
Intervention Name(s)
deucrictibant medium dose
Other Intervention Name(s)
PHVS416, PHA121, PHA-022121
Intervention Description
deucrictibant soft capsules for oral use
Intervention Type
Drug
Intervention Name(s)
deucrictibant high dose
Other Intervention Name(s)
PHVS416, PHA121, PHA-022121
Intervention Description
deucrictibant soft capsules for oral use
Intervention Type
Drug
Intervention Name(s)
deucrictibant selected dose
Other Intervention Name(s)
PHVS416, PHA121, PHA-022121
Intervention Description
deucrictibant soft capsule for oral use
Primary Outcome Measure Information:
Title
Treatment-emergent Adverse Events (TEAEs), treatment-related TEAEs, treatment-emergent serious adverse events (TESAEs), and treatment-related TESAEs
Time Frame
From enrollment through study completion, up to 40 months (dependent on time of enrollment).
Title
Heart Rate
Description
Descriptive in nature, no formal statistical hypothesis testing will be performed.
Time Frame
From enrollment through study completion, up to 40 months (dependent on time of enrollment).
Title
Blood pressure
Description
Systolic and diastolic blood pressure will be measured. Descriptive in nature, no formal statistical hypothesis testing will be performed.
Time Frame
From enrollment through study completion, up to 40 months (dependent on time of enrollment).
Title
Body temperature
Description
Descriptive in nature, no formal statistical hypothesis testing will be performed.
Time Frame
From enrollment through study completion, up to 40 months (dependent on time of enrollment).
Secondary Outcome Measure Information:
Title
Time to onset of symptom relief (TOSR) assessed by the 3- or 5-symptom visual analog scale score (VAS-3 or VAS-5)
Description
VAS-3 (non-laryngeal attacks) and VAS-5 (laryngeal attacks) scores range between 0 and 100. Symptom relief is defined as a 50% or higher reduction of the VAS-3 or VAS-5 score from the pre-treatment value.
Time Frame
Assessed from pre-treatment to 48 hours post-treatment
Title
Time to almost complete or complete symptom relief (TACSR and TCSR) assessed by VAS-3 or VAS-5
Description
VAS scores range between 0 and 100. Almost complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 or VAS-5 having a value < 10. Complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 or VAS-5 having a value of 0.
Time Frame
Assessed from pre-treatment to 48 hours post-treatment
Title
Time to symptom improvement based on patient global impression of severity (PGI-S)
Description
PGI-S evaluates the severity of attack symptoms with a 5-point response scale.
Time Frame
Assessed from pre-treatment to 48 hours post-treatment
Title
Time to symptom improvement based on patient global impression of change (PGI-C)
Description
PGI-C evaluates the change in the attack symptoms over time with a 7-point response scale.
Time Frame
Assessed from pre-treatment to 48 hours post-treatment
Title
Change of VAS-3 score and individual VAS score from pre-treatment to 4 h post-treatment for non-laryngeal attacks
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
Title
Change in Mean symptom complex severity (MSCS) score
Description
MSCS scores range between 0 and 3. A higher score means a worse outcome.
Time Frame
Assessed from pre-treatment to 48 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
Assessed from pre-treatment to 4 hours post-treatment
Title
Proportion of PHA-022121-treated attacks requiring a second dose of PHA-022121
Time Frame
From enrollment through study completion, up to 40 months (dependent on time of enrollment).
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Signed and dated informed consent form Diagnosis of HAE type I or II must have received at least 1 dose of study drug (including the non-attack visit) in Study PHA022121-C201. 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 enrolment History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse Discontinued from Study PHA022121-C201 after enrollment for any study drug-related safety reason. Use of concomitant medications that are potent CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole, ritonavir, grapefruit) or potent CYP3A4 inducers (e.g., phenytoin, rifampicin, St. John's Wort). Participation in any other investigational drug study within defined period
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pharvaris Clinical Team
Phone
+31 (71) 203-6410
Email
clinicaltrials@pharvaris.com
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
Individual Site Status
Active, not recruiting
Facility Name
Study site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Study site
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Study site
City
Sofia
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
Study site
City
Montréal
State/Province
Quebec
Country
Canada
Individual Site Status
Recruiting
Facility Name
Study site
City
Brno
Country
Czechia
Individual Site Status
Recruiting
Facility Name
Study site
City
Grenoble
ZIP/Postal Code
38043
Country
France
Individual Site Status
Recruiting
Facility Name
Study site
City
Paris
ZIP/Postal Code
75010
Country
France
Individual Site Status
Recruiting
Facility Name
Study site
City
Berlin
ZIP/Postal Code
10114
Country
Germany
Individual Site Status
Recruiting
Facility Name
Study site
City
Frankfurt am Main
ZIP/Postal Code
60596
Country
Germany
Individual Site Status
Recruiting
Facility Name
Study site
City
Budapest
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Study site
City
Ashkelon
Country
Israel
Individual Site Status
Recruiting
Facility Name
Study site
City
Kraków
Country
Poland
Individual Site Status
Recruiting
Facility Name
Study site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Study site
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Individual Site Status
Recruiting
Facility Name
Study site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema

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