A Study of STAR-0215 in Participants With Hereditary Angioedema

Study Overview
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Brief Summary
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The goal of this clinical trial is to test the drug STAR-0215 in participants with hereditary angioedema (HAE). One group of participants will get 1 dose of STAR-0215, and two other groups will get 2 doses of STAR-0215. Researchers will study the effects of STAR-0215 in participants with HAE as this is the first time that the drug has been given to participants with HAE.

Detailed Description
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This is a Phase 1b/2 single and multiple dose trial evaluating the safety, tolerability, clinical activity, pharmacokinetics, pharmacodynamics, and immunogenicity of subcutaneous administration of STAR-0215 in participants with type I or type II HAE in 3 dose cohorts. The first cohort will receive 1 dose of STAR-0215; the second and third cohorts will receive 2 sequential doses. This is the first trial of STAR-0215 in participants with HAE and the first evaluation of a multiple-dose regimen.

Official Title
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A Phase 1b/2 Single and Multiple Dose Study to Assess the Safety, Tolerability, Clinical Activity, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of STAR-0215 in Participants With Hereditary Angioedema (The ALPHA-STAR Trial)

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Drug: STAR-0215


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of HAE (type I or II). The following must be met: a. Documented clinical history consistent with HAE (for example, subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria). Experienced at least 2 HAE attacks during the Run-In period, as confirmed by an investigator based on meeting the protocol-specified definition of an HAE attack. Exclusion Criteria: Any concomitant diagnosis of another form of chronic angioedema, such as acquired C1 inhibitor deficiency, HAE with normal C1-INH (also known as HAE type III), idiopathic angioedema, or angioedema associated with urticaria. Use of therapies prescribed for the prevention of HAE attacks prior to Screening: lanadelumab within 90 days berotralstat within 21 days all other prophylactic therapies, within 7 days Any exposure to angiotensin-converting enzyme inhibitors or any estrogen containing medications with systemic absorption (such as hormonal contraceptives or hormone replacement therapy) within 28 days prior to Screening. Any exposure to androgens (for example, stanozolol, danazol, oxandrolone, methyltestosterone, testosterone) within 7 days prior to Screening.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - Single Dose<br>Participants will receive 1 dose of STAR-0215. | Drug: STAR-0215<br>* STAR-0215 will be administered as a subcutaneous bolus injection.<br>|
| Experimental: Cohort 2 - Multiple Dose<br>Participants will receive 2 doses of STAR-0215 administered 3 months apart. | Drug: STAR-0215<br>* STAR-0215 will be administered as a subcutaneous bolus injection.<br>|
| Experimental: Cohort 3 - Multiple Dose<br>Participants will receive 2 doses of STAR-0215 administered 1 month apart. | Drug: STAR-0215<br>* STAR-0215 will be administered as a subcutaneous bolus injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Treatment-emergent Adverse Events |  | Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Monthly HAE Attack Rate |  | Baseline through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3) | 
| Severity of HAE Attacks Experienced by Participants | All HAE attacks will be classified according to severity (mild, moderate, and severe). | Cohort 1: Day 1 through Day 168; Cohort 2: Day 1 through Day 251; Cohort 3: Day 1 through Day 195 | 
| Duration of HAE Attacks | Duration will be reported as shorter than 12 hours, 12 to 24 hours, 24 to 48 hours, and longer than 48 hours. | Cohort 1: Day 1 through Day 168; Cohort 2: Day 1 through Day 251; Cohort 3: Day 1 through Day 195 | 
| Number of Participants Experiencing HAE Attacks Requiring On-demand Therapy |  | Cohort 1: Day 1 through Day 168; Cohort 2: Day 1 through Day 251; Cohort 3: Day 1 through Day 195 | 
| Time to First HAE Attack After First and Last Dosing |  | Cohort 1: Day 1 through Day 168; Cohort 2: Day 1 through Day 251; Cohort 3: Day 1 through Day 195 | 
| Serum Concentration of STAR-0215 | Blood samples will be collected to measure the serum concentration of STAR-0215 before and after study drug administration. | Cohort 1: Day 1 (pre-dose, 4 hours post dose) up to Day 168; Cohort 2: Days 1 and 84 (pre-dose, 4 hours post dose) up to Day 251; Cohort 3: Days 1 and 28 (pre-dose, 4 hours post dose) up to Day 195 | 
| Plasma Levels of Cleaved High-molecular-weight Kininogen | Blood samples will be collected to measure the plasma levels of cleaved high-molecular-weight kininogen (a measure of plasma kallikrein activity). | Cohort 1: Day 1 (pre-dose, 4 hours post dose) up to Day 168; Cohort 2: Days 1 and 84 (pre-dose, 4 hours post dose) up to Day 251; Cohort 3: Days 1 and 28 (pre-dose, 4 hours post dose) up to Day 195 | 
| Number of Participants with Anti-drug Antibodies To STAR-0215 | Blood samples will be collected to assess the formation of STAR-0215 anti-drug antibodies in serum before and after study drug administration. | Cohort 1: Day 1 (pre-dose); Days 14, 28, 56, 84, 112, 140, and 168; Cohort 2: Days 1 and 84 (pre-dose); Days 14, 28, 56, 111, 167, and 251; Cohort 3: Days 1 and 28 (pre-dose); Days 14, 55, 111, and 195 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAE, Angioedema