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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: 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
• Intervention / Treatment: Drug: deucrictibant low dose; Drug: deucrictibant medium dose; Drug: deucrictibant high dose; Drug: deucrictibant selected dose

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.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Pharvaris Clinical Team; Phone Number: +31 (71) 203-6410; Email: clinicaltrials@pharvaris.com

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Recruiting
    • Study Site
• Canada
  • Quebec
    • Montréal, Quebec, Canada
      • Recruiting
      • Study Site
• Czechia
  • Brno, Czechia
    • Recruiting
    • Study Site
• France
  • Grenoble, France, 38043
    • Recruiting
    • Study Site
  • Paris, France, 75010
    • Recruiting
    • Study Site
• Germany
  • Berlin, Germany, 10114
    • Recruiting
    • Study Site
  • Frankfurt am Main, Germany, 60596
    • Recruiting
    • Study Site
• Hungary
  • Budapest, Hungary
    • Recruiting
    • Study Site
• Israel
  • Ashkelon, Israel
    • Recruiting
    • Study Site
• Poland
  • Kraków, Poland
    • Recruiting
    • Study Site
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Study Site
  • Barcelona, Spain, 08907
    • Recruiting
    • Study Site
  • Madrid, Spain, 28007
    • Recruiting
    • Study Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Active, not recruiting
      • Study Site
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Active, not recruiting
      • Study Site
  • California
    • Walnut Creek, California, United States, 94598
      • Active, not recruiting
      • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Low dose; Single low dose of deucrictibant	Drug: deucrictibant low dose; deucrictibant soft capsules for oral use; Other Names: PHVS416; PHA121; PHA-022121
Experimental: Part A: Medium dose; Single medium dose of deucrictibant	Drug: deucrictibant medium dose; deucrictibant soft capsules for oral use; Other Names: PHVS416; PHA121; PHA-022121
Experimental: Part A: High dose; Single high dose of deucrictibant	Drug: deucrictibant high dose; deucrictibant soft capsules for oral use; Other Names: PHVS416; PHA121; PHA-022121
Experimental: Part B: Selected dose; Single dose of deucrictibant	Drug: deucrictibant selected dose; deucrictibant soft capsule for oral use; Other Names: PHVS416; PHA121; PHA-022121

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).
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).
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).
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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).
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

Collaborators and Investigators

• Sponsor: Pharvaris Netherlands B.V.
• Investigators: Principal Investigator: Marcus Maurer, Prof MD, Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: April 28, 2022
• First Submitted That Met QC Criteria: May 24, 2022
• First Posted (Actual): May 31, 2022

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: HAE; HAE Type I; HAE Type II; Oral Treatment; Bradykinin B2 Receptor Antagonists; PHVS416; PHA121; On-Demand; PHA-022121; Deucrictibant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II
• Other Study ID Numbers: PHA022121-C303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No