Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II

Study Overview
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Brief Summary
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This study evaluates the safety and efficacy of PHA-022121 administered orally for prophylaxis against angioedema attacks in patients with hereditary angioedema (HAE). The study consists of 2 parts, with patients completing participation in Part 1 prior to initiation of treatment in Part 2. Part 1 of the study has 3 parallel arms and approximately 30 patients will be equally randomized to one of two dose regimens of PHA-022121 or matching placebo. Patients will continue to the single open-label arm in Part 2 of the study after completion of Part 1. The screening period is up to 8 weeks and the treatment periods are 12 weeks (Part 1) and 30 months (Part 2) in duration.

Official Title
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A Phase II, Double-blind, Placebo-controlled, Randomized, Dose-ranging, Parallel Group Study to Evaluate the Safety and Efficacy of PHA-022121 Administered Orally for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Due to C1-Inhibitor Deficiency (Type I or Type II)

Conditions
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Hereditary Angioedema Type II, Hereditary Angioedema, Hereditary Angioedema Type I, 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
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* Drug: Deucrictibant low dose
* Drug: Deucrictibant high dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent form Diagnosis of HAE type I or II Documented history of at least 3 HAE attacks within the last 3 consecutive months prior to screening, or a minimum of 2 HAE attacks during the screening period Reliable access and experience to use standard of care acute attack medications 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 enrolment Abnormal hepatic function Abnormal renal function History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Low dose<br>BID low dose of deucrictibant | Drug: Deucrictibant low dose<br>* Deucrictibant softgel capsules for oral use (PHVS416)<br>|
| Experimental: Part 1: High dose<br>BID high dose of deucrictibant | Drug: Deucrictibant high dose<br>* Deucrictibant softgel capsules for oral use (PHVS416)<br>|
| Placebo Comparator: Part 1: Placebo<br>BID placebo | Drug: Placebo<br>* Matching placebo capsules for oral use<br>|
| Experimental: Part 2: Open-label<br>BID high dose of deucrictibant | Drug: Deucrictibant high dose<br>* Deucrictibant softgel capsules for oral use (PHVS416)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of investigator-confirmed HAE attacks |  | Day 0 to Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of investigator-confirmed moderate or severe HAE attacks during the treatment period |  | Day 0 to Day 84 | 
| Number of investigator-confirmed HAE attacks requiring acute treatment during the treatment period |  | Day 0 to Day 84 | 
| Number of patients achieving reduction in attack rate during the treatment period relative to baseline |  | Day 0 to Day 84 | 
| Number of patients that are attack-free during the treatment period |  | Day 0 to Day 84 | 
| Number and proportion of days with angioedema symptoms during the treatment period |  | Day 0 to Day 84 | 
| Time to first investigator-confirmed HAE attack in the treatment period |  | Day 0 to Day 84 | 
| Number of investigator-confirmed HAE attacks resulting in a visit to the emergency department or an admission to hospital |  | Day 0 to Day 84 | 
| Number of investigator-confirmed angioedema attacks during the treatment period in Part 2. |  | Day 84 to Day 938 | 
| Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period in Part 2. |  | Day 84 to Day 938 | 
| Number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period in Part 2. |  | Day 84 to Day 938 | 
| Incidence of HAE attacks during the treatment period in Part 2 (attack rate trend over time). |  | Day 84 to Day 938 | 
| Number and proportion of days with angioedema symptoms during the treatment period in Part 2. |  | Day 84 to Day 938 | 

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