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

Hereditary Angioedema Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04618211
• Other study ID #: PHA022121-C201
• Secondary ID: 2020-003445-11
• Status: Completed
• Phase: Phase 2
• Start date: February 3, 2021
• Est. completion date: March 1, 2023

Study information

• Verified date: June 2023
• Source: Pharvaris Netherlands B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: March 1, 2023
• Est. primary completion date: September 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Angioedema
• C1 Esterase Inhibitor Deficiency
• C1 Inhibitor Deficiency
• Hereditary Angioedema
• Hereditary Angioedema - Type 1
• Hereditary Angioedema - Type 2
• Hereditary Angioedema Attack
• Hereditary Angioedema Type I
• Hereditary Angioedema Type II
• Hereditary Angioedema Types I and II
• Hereditary Angioedema With C1 Esterase Inhibitor Deficiency

Intervention

Drug:
• Deucrictibant
deucrictibant soft capsules for oral use
• Placebo
Matching placebo capsules for oral use

Locations

Country	Name	City	State
Bulgaria	Study site	Sofia
Canada	Study site	Edmonton	Alberta
Canada	Study site	Montréal	Quebec
Canada	Study site	Ottawa	Ontario
Canada	Study site	Québec City	Quebec
Canada	Study site	Toronto	Ontario
Czechia	Study site	Brno
Czechia	Study site	Hradec Králové
France	Study site	Grenoble
France	Study site	Montpellier
France	Study site	Paris
Germany	Study site	Berlin
Germany	Study site	Dresden
Germany	Study site	Frankfurt
Germany	Study site	Mainz
Germany	Study site	Ulm
Hungary	Study site	Budapest
Israel	Study site	Ashkelon
Israel	Study site	Haifa
Israel	Study site	Tel Aviv
Italy	Study site	Monserrato
Italy	Study site	Naples
Netherlands	Study site	Amsterdam
Poland	Study site	Kraków
Spain	Study site	Barcelona
Spain	Study site	Madrid
United Kingdom	Study site	Brighton
United Kingdom	Study site	London
United States	Study site	Birmingham	Alabama
United States	Study site	Chevy Chase	Maryland
United States	Study site	Hershey	Pennsylvania
United States	Study site	Paradise Valley	Arizona
United States	Study site	Saint Louis	Missouri
United States	Study site	San Diego	California
United States	Study site	Santa Monica	California
United States	Study site	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Pharvaris Netherlands B.V.

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Pre-treatment and 4 hours post-treatment
Secondary	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.	Assessed from pre-treatment to 48 hours post-treatment
Secondary	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.	Assessed at 4 hours post-study drug treatment
Secondary	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.	Assessed from pre-treatment to 48 hours post-treatment
Secondary	Mean symptom complex severity (MSCS) score	MSCS scores range between 0 and 3. A higher score means a worse outcome.	4 hours post-treatment
Secondary	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.	Pre-treatment and 4 hours post-treatment
Secondary	Treatment satisfaction questionnaire for medication (TSQM) scores	TSQM scores range from 0 to 100. A higher score means a better outcome.	48 hours post-treatment
Secondary	Treatment-emergent adverse events (TEAEs)		From post-dose non-attack visit through study completion, approximately 26 weeks
Secondary	Treatment-related adverse events (AEs)		From post-dose non-attack visit through study completion, approximately 26 weeks
Secondary	Treatment-emergent serious adverse events (TESAEs)		From post-dose non-attack visit through study completion, approximately 26 weeks