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

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

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.

Study Overview

• Status: Completed
• 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 Deficiency; C1 Inhibitor Deficiency
• Intervention / Treatment: Drug: Placebo; Drug: Deucrictibant

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).

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Study Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • Study Site
  • Ontario
    • Ottawa, Ontario, Canada
      • Study Site
    • Toronto, Ontario, Canada
      • Study Site
  • Quebec
    • Montreal, Quebec, Canada
      • Study Site
    • Québec, Quebec, Canada
      • Study Site
• Czechia
  • Brno, Czechia
    • Study Site
  • Hradec Králové, Czechia
    • Study Site
• France
  • Grenoble, France
    • Study Site
  • Montpellier, France
    • Study Site
  • Paris, France
    • Study Site
• Germany
  • Berlin, Germany
    • Study Site
  • Dresden, Germany
    • Study Site
  • Frankfurt, Germany
    • Study Site
  • Mainz, Germany
    • Study Site
  • Ulm, Germany
    • Study Site
• Hungary
  • Budapest, Hungary
    • Study Site
• Israel
  • Ashkelon, Israel
    • Study Site
  • Haifa, Israel
    • Study Site
  • Tel Aviv, Israel
    • Study Site
• Italy
  • Monserrato, Italy
    • Study Site
  • Naples, Italy
    • Study Site
• Netherlands
  • Amsterdam, Netherlands
    • Study Site
• Poland
  • Krakow, Poland
    • Study Site
• Spain
  • Barcelona, Spain
    • Study Site
  • Madrid, Spain
    • Study Site
• United Kingdom
  • Brighton, United Kingdom
    • Study Site
  • London, United Kingdom
    • Study Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Study Site
  • Arizona
    • Paradise Valley, Arizona, United States, 85253
      • Study Site
  • California
    • San Diego, California, United States, 92122
      • Study Site
    • Santa Monica, California, United States, 90404
      • Study Site
    • Walnut Creek, California, United States, 94598
      • Study Site
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Study Site
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Study Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (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. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Low dose/placebo; Single low dose of deucrictibant or placebo	Drug: Placebo; Matching placebo capsules for oral use; Drug: Deucrictibant; deucrictibant soft capsules for oral use; Other Names: PHVS416; PHA121; PHA-022121
Other: Medium dose/placebo; Single medium dose of deucrictibant or placebo	Drug: Placebo; Matching placebo capsules for oral use; Drug: Deucrictibant; deucrictibant soft capsules for oral use; Other Names: PHVS416; PHA121; PHA-022121
Other: High dose/placebo; Single high dose of deucrictibant or placebo	Drug: Placebo; Matching placebo capsules for oral use; Drug: Deucrictibant; deucrictibant soft capsules for oral use; Other Names: PHVS416; PHA121; PHA-022121

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the 3-symptom Composite Visual Analogue Scale (VAS-3) Score From Pre-treatment to 4 Hours Post-treatment	The primary endpoint of the study was the change of the VAS-3 (3-symptom composite visual analogue scale) score from pre-treatment to 4 hours post-treatment. The VAS-3 was calculated as the mean of the VAS scores of the 3 major HAE symptoms: skin swelling, skin pain, and abdominal pain. The VAS scores of the 3 major HAE symptoms (skin swelling, skin pain, and abdominal pain) could range between 0 (No swelling/No pain) and 100 (Extreme swelling/Excruciating pain)	Assessed from pre-treatment to 4 hours post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Onset of Symptom Relief by ≥30% Reduction in Visual Analogue Scale (VAS-3) Composite Score From the Pre-treatment Score	VAS-3 scores range between 0 and 100.	Assessed from pre-treatment to 48-hours post-treatment
Time to Onset of Almost Complete or 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
Time to a ≥50% Reduction in VAS-3 Composite Score From the Pre-treatment Score	Time to a ≥50% reduction in VAS-3 composite score from the pre-treatment score.	Assessed from pre-treatment to 48 hours post-treatment
Change in the Mean Symptom Complex Severity (MSCS) Score From Pre-treatment to 4 Hours Post-treatment	MSCS scores range between 0 and 3. A higher score means a worse outcome.	Pre-treatment and 4 hours post-treatment
Treatment Outcome Score (TOS) at 4 Hours Post-treatment	TOS 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.	4 hours post-treatment
Time to Onset of Primary Symptom Relief Assessed by a 30% Reduction in the VAS for the Primary Symptom	Time to onset of primary symptom relief assessed by a 30% reduction in the VAS for the primary symptom within 48 hours post-treatment	Within 48 hours post-treatment
Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 12 Hours.	Proportion of blinded study drug treated attacks requiring HAE rescue medication within 12 hours post-treatment.	Assessed at 12 hours post study drug treatment
Time to First HAE Rescue Medication Use for Study Drug-treated Attacks Within 48 Hours Post-treatment	The proportion of treated attacks with first use of HAE rescue medication within 48 hours post-treatment with PHA-022121.	Assessed at 48 hours post study drug treatment
Time to Change in the VAS Score for Skin Pain Score - 30% Reduction	Time to change in the VAS score for Skin Pain Score - 30% reduction within 48-hours post-treatment. VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.	Within 48 hours post treatment
Change in Mean Symptom Complex Severity Score From Pre-treatment to 24 Hours Post-treatment	Change in the Mean Symptom Complex Severity (MSCS) score from pre-treatment to 24 hours post-treatment. A lower MSCS score indicates a better outcome.	24 hours post-treatment
TOS at 24 Hours Post-treatment	Treatment outcome score at 24 hours post-treatment. A higher score indicates improvement.	Assessed within 24 hours post treatment
Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Effectiveness Domain Score	MMRM analysis of Treatment Satisfaction Questionnaire for Medication (TSQM) at 48 hours post-treatment. The 11-item TSQM (version II) evaluated participant treatment satisfaction with the medication for the following scales: effectiveness, side effects, convenience, and overall satisfaction Scale scores were transformed into scores ranging from 0 to 100 and could be used to calculate a total composite score, a higher score indicating greater satisfaction.	48 hours post-treatment
Time to Onset of Primary Symptom Relief by 50% Reduction in VAS Score	Time to Onset of Primary Symptom Relief by 50% Reduction in VAS Score within 48 hours post-treatment. VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.	Within 48 hours post-treatment
Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours.	Qualifying attacks treated with study drug may use approved rescue medication if no symptom relief within 4 hours has been experienced.	Assessed at 24 hours post-study drug treatment
Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours	Qualifying attacks treated with study drug may use approved rescue medication if no symptom relief within 4 hours has been experienced.	Assessed at 48 hours post-study drug treatment
Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Convenience Domain Score	MMRM analysis of Treatment Satisfaction Questionnaire for Medication (TSQM) at 48 hours post-treatment. The 11-item TSQM (version II) evaluated participant treatment satisfaction with the medication for the following scales: effectiveness, side effects, convenience, and overall satisfaction Scale scores were transformed into scores ranging from 0 to 100 and could be used to calculate a total composite score, a higher score indicating greater satisfaction.	48 hours post-treatment
Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Satisfaction Domain Score	MMRM analysis of Treatment Satisfaction Questionnaire for Medication (TSQM) at 48 hours post-treatment. The 11-item TSQM (version II) evaluated participant treatment satisfaction with the medication for the following scales: effectiveness, side effects, convenience, and overall satisfaction Scale scores were transformed into scores ranging from 0 to 100 and could be used to calculate a total composite score, a higher score indicating greater satisfaction.	48 hours post-treatment
Time to Change in the VAS Score for Skin Swelling Score - 30% Reduction	Time to change in the VAS score for Skin Swelling Score - 30% reduction within 48 hours post-treatment. VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.	Within 48 hours post-treatment
Time to Change in the VAS Score for Abdominal Pain Score - 30% Reduction	Time to change in the VAS score for Abdominal Pain Score - 30% reduction within 48 hours post-treatment. VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.	Within 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): February 3, 2021
• Primary Completion (Actual): September 23, 2022
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: November 4, 2020
• First Posted (Actual): November 5, 2020

Study Record Updates

• Last Update Posted (Estimated): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: HAE; HAE Type I; HAE Type II; Oral Treatment; Bradykinin B2 Receptor Antagonists; PHVS416; PHA121; PHA-022121; Deucrictibant
• Additional Relevant MeSH Terms: Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immunologic Deficiency Syndromes; Skin Diseases; Urticaria; Skin Diseases, Vascular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II
• Other Study ID Numbers: PHA022121-C201; 2020-003445-11 (EudraCT Number)

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