A Study of Navenibart (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 navenibart in participants with hereditary angioedema (HAE). One group of participants will get 1 dose of navenibart, and 2 other groups will get 2 doses of navenibart. Researchers will study the effects of navenibart in participants with HAE as this is the first time that the drug has been given to participants with HAE.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema
• Intervention / Treatment: Drug: Navenibart

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 navenibart in participants with type I or type II HAE in 3 dose cohorts. The first cohort will receive 1 dose of navenibart; the second and third cohorts will receive 2 sequential doses. This is the first trial of navenibart in participants with HAE and the first evaluation of a multiple-dose regimen. After the required follow up period, participants who are willing and eligible to consent can begin participation in the long-term open label extension study (STAR-0215-202, ALPHA-SOLAR; NCT06007677).

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1680
    • Diagnostical Consultative Center Convex Ltd.
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2R3
      • University of Alberta
  • Ontario
    • Ottawa, Ontario, Canada, K1H 1E4
      • Ottawa Allergy Research Corporation
• Czechia
  • Hradec Králové, Czechia, 500 05
    • Institute of Clinical Immunology/Allergology, Faculty Hospital
• Germany
  • Berlin, Germany, 12203
    • Charité Universitätsmedizin Berlin
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • Leeds, United Kingdom, LS9 7TF
    • St. James's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Allervie Clinical Research
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Medical Research of Arizona a Division of Allergy, Asthma & Immunology Associates, LTD.
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Allergy & Asthma Clinic of Northwest Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Acuro Research, Inc.
  • California
    • San Diego, California, United States, 92122
      • UC San Diego US HAEA Angioedema Center
    • Santa Monica, California, United States, 90404
      • Raffi Tachdjian MD, Inc
    • Walnut Creek, California, United States, 94598
      • Allergy & Asthma Clinical Research
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Institute for Asthma and Allergy, PC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43235
      • Optimed Research
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health Milton S. Hershey Medical Center
  • Texas
    • Dallas, Texas, United States, 75231
      • AARA Research Center

Participation Criteria

Eligibility Criteria

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

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 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 - Single Dose; Participants received 1 dose (450 milligrams [mg]) of navenibart.	Drug: Navenibart; Navenibart will be administered as a subcutaneous bolus injection.; Other Names: STAR-0215
Experimental: Cohort 2 - Multiple Dose; Participants received 2 doses (600 mg, 300 mg) of navenibart administered 3 months apart.	Drug: Navenibart; Navenibart will be administered as a subcutaneous bolus injection.; Other Names: STAR-0215
Experimental: Cohort 3 - Multiple Dose; Participants received 2 doses (600 mg) of navenibart administered 1 month apart.	Drug: Navenibart; Navenibart will be administered as a subcutaneous bolus injection.; Other Names: STAR-0215

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Treatment-emergent Adverse Events	An adverse event was any untoward medical occurrence in a clinical investigation participant who was administered a pharmaceutical product that did not necessarily have a causal relationship with the treatment. A treatment-emergent adverse event was defined as any adverse event with an onset at the time of or following the start of treatment with study drug, or medical conditions present before the start of treatment that increased in severity or relationship at the time of or following the start of treatment. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' section.	Day 1 through Day 448 (Cohort 1), Day 531 (Cohort 2), Day 475 (Cohort 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Monthly Hereditary Angioedema (HAE) Attack Rate	An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). The HAE attack rate was the number of unique investigator-confirmed HAE attacks per month.	Baseline, Day 168 (Cohort 1), Day 251 (Cohort 2), Day 195 (Cohort 3)
Number of Participants Who Were HAE Attack Free	An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).	Baseline through Day 168 (Cohort 1), Day 251 (Cohort 2), Day 195 (Cohort 3)
Severity of HAE Attacks Experienced by Participants	An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). All HAE attacks were classified by the investigator according to severity: mild (transient or mild discomfort); moderate (mild to moderate limitation in activity, some assistance with daily activities needed); severe (marked limitation in activity, assistance with daily activities required).	Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3)
Duration of HAE Attacks	An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).	Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3)
Number of HAE Attacks Requiring On-demand Therapy	An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).	Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3)
Time to First HAE Attack After First and Last Dosing	An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). The time to first HAE attack was calculated by: ([First HAE attack or censor date] - First Treatment date) +1. If a participant did not have an HAE attack, they were censored to the end of study date.	Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3)
Proportion of HAE Attack-free Days	An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). The proportion of HAE attack-free days was calculated by: (the number of HAE attack-free days/duration of evaluation period in days).	Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3)
Maximum Drug Concentration (Cmax) of Navenibart	Blood samples were collected at designated timepoints to measure the Cmax of navenibart. Results reported as micrograms/milliliter (mcg/mL).	Day 1 (pre-dose, 4 hours post dose) up to Day 168 (Cohort 1); Day 1 (pre-dose, 4 hours post dose) up to Day 251 (Cohort 2); Day 1 (pre-dose, 4 hours post dose) up to Day 195 (Cohort 3)
Percent Change From Baseline in Plasma Levels of Cleaved High-molecular-weight Kininogen (cHMWK)	Blood samples were collected to measure the plasma levels of cHMWK (a measure of plasma kallikrein activity). Results reported as percent change in percentage cHMWK (%cHMWK). A decrease in %cHMWK is reflective of the pharmacodynamic activity of navenibart.	Baseline, Day 56 (Cohort 1), Day 90 (Cohort 2), Day 41 (Cohort 3)
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) to Navenibart	Blood samples were collected at designated timepoints to assess the formation of navenibart ADAs in serum.	Day 1 (pre-dose) up to Day 168 (Cohort 1); Day 1 (pre-dose) up to Day 251 (Cohort 2); Day 1 (pre-dose) up to Day 195 (Cohort 3)

Collaborators and Investigators

• Sponsor: Astria Therapeutics, Inc.

Publications and helpful links

General Publications

• Banerji A, Craig T, Sitz K, Li HH, Lumry W, Adatia A, Yang W, Jacobs JS, Tachdjian R, Soong W, Manning M, Wedner J, Savic S, Manson A, Valerieva A, Gunsior M, Mugundu G, Cohen T, Bernard K, VanEenwyk C, Joseph K, Best JM, Morabito C, Riedl MA. Open-label phase 1b/2 trial of navenibart, a long-acting plasma kallikrein inhibitor for hereditary angioedema. J Allergy Clin Immunol. 2026 Mar 5:S0091-6749(26)00171-5. doi: 10.1016/j.jaci.2026.02.034. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2023
• Primary Completion (Actual): March 13, 2025
• Study Completion (Actual): March 13, 2025

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): May 8, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: HAE; Angioedema
• Additional Relevant MeSH Terms: Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immunologic Deficiency Syndromes; Skin Diseases; Urticaria; Skin Diseases, Vascular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Angioedema; Angioedemas, Hereditary
• Other Study ID Numbers: STAR-0215-201; 2022-502953-32 (EudraCT Number)

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
• product manufactured in and exported from the U.S.: No