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

Hereditary Angioedema Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05396105
• Other study ID #: PHA022121-C303
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 28, 2022
• Est. completion date: December 2024

Study information

• Verified date: May 2023
• Source: Pharvaris Netherlands B.V.
• Contact: Pharvaris Clinical Team
• Phone: +31 (71) 203-6410
• Email: clinicaltrials[@]pharvaris.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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 low dose
deucrictibant soft capsules for oral use
• deucrictibant medium dose
deucrictibant soft capsules for oral use
• deucrictibant high dose
deucrictibant soft capsules for oral use
• deucrictibant selected dose
deucrictibant soft capsule for oral use

Locations

Country	Name	City	State
Bulgaria	Study site	Sofia
Canada	Study site	Montréal	Quebec
Czechia	Study site	Brno
France	Study site	Grenoble
France	Study site	Paris
Germany	Study site	Berlin
Germany	Study site	Frankfurt am Main
Hungary	Study site	Budapest
Israel	Study site	Ashkelon
Poland	Study site	Kraków
Spain	Study site	Barcelona
Spain	Study site	Barcelona
Spain	Study site	Madrid
United States	Study site	Birmingham	Alabama
United States	Study site	Scottsdale	Arizona
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,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-emergent Adverse Events (TEAEs), treatment-related TEAEs, treatment-emergent serious adverse events (TESAEs), and treatment-related TESAEs		From enrollment through study completion, up to 40 months (dependent on time of enrollment).
Primary	Heart Rate	Descriptive in nature, no formal statistical hypothesis testing will be performed.	From enrollment through study completion, up to 40 months (dependent on time of enrollment).
Primary	Blood pressure	Systolic and diastolic blood pressure will be measured. Descriptive in nature, no formal statistical hypothesis testing will be performed.	From enrollment through study completion, up to 40 months (dependent on time of enrollment).
Primary	Body temperature	Descriptive in nature, no formal statistical hypothesis testing will be performed.	From enrollment through study completion, up to 40 months (dependent on time of enrollment).
Secondary	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.	Assessed from pre-treatment to 48 hours post-treatment
Secondary	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.	Assessed from pre-treatment to 48 hours post-treatment
Secondary	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.	Assessed from pre-treatment to 48 hours post-treatment
Secondary	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.	Assessed from pre-treatment to 48 hours post-treatment
Secondary	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.	Pre-treatment and 4 hours post-treatment
Secondary	Change in Mean symptom complex severity (MSCS) score	MSCS scores range between 0 and 3. A higher score means a worse outcome.	Assessed from pre-treatment to 48 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.	Assessed from pre-treatment to 4 hours post-treatment
Secondary	Proportion of PHA-022121-treated attacks requiring a second dose of PHA-022121		From enrollment through study completion, up to 40 months (dependent on time of enrollment).
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