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

Phase 2

Completed

• Conditions: Hereditary Angioedema - Type 1; Hereditary Angioedema; Hereditary Angioedema - Type 2; Hereditary Angioedema Type I; Hereditary Angioedema Type II; Hereditary Angioedema Types I and II; Hereditary Angioedema Attack; C1 Inhibitor Deficiency; Hereditary Angioedema With C1 Esterase Inhibitor Deficiency; C1 Esterase Inhibitor Deficiency
• Interventions: Drug: Deucrictibant; Drug: Placebo

• Registration Number: NCT04618211
• Lead Sponsor: Pharvaris Netherlands B.V.

Brief 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.

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).

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2020-10-26
• Study First Submitted QC: 2020-11-04
• Study First Posted: 2020-11-05
• Study Start: 2021-02-03
• Primary Completion: 2022-09-23
• Study Completion: 2023-03-01
• Status Verified: 2023-06
• Disposition First Submitted: 2023-06-15
• Last Update Submitted: 2023-06-19
• Disposition First Posted: 2023-06-22
• Last Update Posted: 2023-06-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 74

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
High dose/placebo	Deucrictibant	Single high dose of deucrictibant or placebo
High dose/placebo	Placebo	Single high dose of deucrictibant or placebo
Medium dose/placebo	Placebo	Single medium dose of deucrictibant or placebo
Low dose/placebo	Deucrictibant	Single low dose of deucrictibant or placebo
Low dose/placebo	Placebo	Single low dose of deucrictibant or placebo
Medium dose/placebo	Deucrictibant	Single medium dose of deucrictibant or placebo

Primary Outcome Measures

Name	Time	Method
Change of the 3-symptom composite visual analogue scale (VAS-3) score from pre-treatment to 4 hours post-treatment	Pre-treatment and 4 hours post-treatment	VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.

Secondary Outcome Measures

Name	Time	Method
Treatment-emergent adverse events (TEAEs)	From post-dose non-attack visit through study completion, approximately 26 weeks
Time to onset of almost complete and complete symptom relief by visual analogue scale (VAS-3)	Assessed from pre-treatment to 48 hours post-treatment	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.
Mean symptom complex severity (MSCS) score	4 hours post-treatment	MSCS scores range between 0 and 3. A higher score means a worse outcome.
Treatment-emergent serious adverse events (TESAEs)	From post-dose non-attack visit through study completion, approximately 26 weeks
Proportion of study drug treated attacks requiring HAE rescue medication	Assessed at 4 hours post-study drug treatment	Qualifying attacks treated with study drug may use approved rescue medication if no symptom relief within 4 h has been experienced.
Treatment satisfaction questionnaire for medication (TSQM) scores	48 hours post-treatment	TSQM scores range from 0 to 100. A higher score means a better outcome.
Treatment-related adverse events (AEs)	From post-dose non-attack visit through study completion, approximately 26 weeks
Time to onset of symptom relief by visual analogue scale (VAS-3) score	Assessed from pre-treatment to 48 hours post-treatment	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.
Treatment outcome score (TOS)	Pre-treatment and 4 hours post-treatment	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.

Trial Locations

Locations (1)

Study site; 🇬🇧 London, United Kingdom