A Study of STAR-0215 in Participants With Hereditary Angioedema

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)

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 the other group 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hereditary Angioedema
• Intervention / Treatment: Drug: STAR-0215

Detailed Description

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 2 dose cohorts. The first cohort will receive 1 dose of STAR-0215; the second cohort 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.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Christopher Morabito, MD; Phone Number: 1-617-349-1971; Email: [email protected]

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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).

2. Experienced at least 4 HAE attacks within the 12 months prior to Screening, per participant report.
3. 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:

1. 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.

2. Use of therapies prescribed for the prevention of HAE attacks prior to Screening:

   1. lanadelumab within 90 days
   2. berotralstat within 21 days
   3. all other prophylactic therapies, within 7 days
3. 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.
4. Any exposure to androgens (for example, stanozolol, danazol, oxandrolone, methyltestosterone, testosterone) within 7 days prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Experiencing Treatment-emergent Adverse Events	Day 1 through Day 168 (Cohort 1) and Day 251 (Cohort2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline In Monthly HAE Attack Rate		Baseline through Day 168 (Cohort 1) and Day 251 (Cohort 2)
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
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
Number of Participants Experiencing HAE Attacks Requiring On-demand Therapy		Cohort 1: Day 1 through Day 168; Cohort 2: Day 1 through Day 251
Time To First HAE Attack After First And Last Dosing		Cohort 1: Day 1 through Day 168; Cohort 2: Day 1 through Day 251
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-infusion, up to 4 hours post dose); Days 2, 7, 14, 28, 56, 84, 112, 140, and 168; Cohort 2: Days 1 and 84 (pre-infusion, up to 4 hours post dose); Days 2, 7, 14, 28, 56, 85, 90, 97, 111, 139, 167, 209, and 251
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-infusion, up to 4 hours post dose); Days 2, 7, 14, 28, 56, 84, 112, 140, and 168; Cohort 2: Days 1 and 84 (pre-infusion, up to 4 hours post dose); Days 2, 7, 14, 28, 56, 85, 90, 97, 111, 139, 167, 209, and 251
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-infusion); Days 14, 28, 56, 84, 112, 140, and 168; Cohort 2: Days 1 and 84 (pre-infusion); Days 14, 28, 56, 111, 167, and 251

Collaborators and Investigators

• Sponsor: Astria Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2023
• Primary Completion (Anticipated): November 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: January 6, 2023
• First Submitted That Met QC Criteria: January 13, 2023
• First Posted (Actual): January 23, 2023

Study Record Updates

• Last Update Posted (Actual): January 23, 2023
• Last Update Submitted That Met QC Criteria: January 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: HAE; Angioedema
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary
• Other Study ID Numbers: STAR-0215-201

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