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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

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

Intervention / Treatment
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* Drug: Deucrictibant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Signed and dated informed consent form Diagnosis of HAE type I or II 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 Reliable access and experience to use standard of care acute attack medications Key Exclusion Criteria: Pregnancy or breast-feeding Clinically significant abnormal electrocardiogram Any other systemic disease or significant disease or disorder that would interfere with the patient's safety or ability to participate in the study Use of C1-esterase inhibitor, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy within a defined period prior to enrollment Positive serology for HIV or active infection with hepatitis B virus or hepatitis C virus Abnormal hepatic function Abnormal renal function History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse History of documented severe hypersensitivity to any medicinal product Participation in any other investigational drug study within defined period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Low dose/placebo<br>Single low dose of deucrictibant or placebo | Drug: Deucrictibant<br>* deucrictibant soft capsules for oral use<br>* Other names: PHVS416;Drug: Placebo<br>* Matching placebo capsules for oral use<br>|
| Other: Medium dose/placebo<br>Single medium dose of deucrictibant or placebo | Drug: Deucrictibant<br>* deucrictibant soft capsules for oral use<br>* Other names: PHVS416;Drug: Placebo<br>* Matching placebo capsules for oral use<br>|
| Other: High dose/placebo<br>Single high dose of deucrictibant or placebo | Drug: Deucrictibant<br>* deucrictibant soft capsules for oral use<br>* Other names: PHVS416;Drug: Placebo<br>* Matching placebo capsules for oral use<br>|

What is the study measuring?
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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 | VAS-3 scores range between 0 and 100. A larger reduction means a better outcome. | Pre-treatment and 4 hours post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| Mean symptom complex severity (MSCS) score | MSCS scores range between 0 and 3. A higher score means a worse outcome. | 4 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. | Pre-treatment and 4 hours post-treatment | 
| 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 | 
| Treatment-emergent adverse events (TEAEs) |  | From post-dose non-attack visit through study completion, approximately 26 weeks | 
| Treatment-related adverse events (AEs) |  | From post-dose non-attack visit through study completion, approximately 26 weeks | 
| Treatment-emergent serious adverse events (TESAEs) |  | From post-dose non-attack visit through study completion, approximately 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAE Type I, HAE Type II, Oral Treatment, Bradykinin B2 Receptor Antagonists, PHVS416, PHA121, HAE, PHA-022121, Deucrictibant