A Study of Navenibart in Participants With Hereditary Angioedema (ALPHA-ORBIT)

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Navenibart in Participants With Hereditary Angioedema (HAE)

This is a Phase 3 multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of subcutaneous administration of navenibart in adult and adolescent participants with type 1 or type 2 hereditary angioedema (HAE). The goal of this clinical trial is to evaluate the efficacy and safety of navenibart compared to placebo in preventing HAE attacks in participants with HAE.

Study Overview

• Status: Enrolling by invitation
• Conditions: Hereditary Angioedema (HAE)
• Intervention / Treatment: Drug: navenibart; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 145
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Murdoch, Australia, WA 6150
    • Site 74
  • New South Wales
    • Campbelltown, New South Wales, Australia, 2560
      • Site 68
  • Victoria
    • Melbourne, Victoria, Australia
      • Site 76
• Austria
  • Vienna, Austria, 1090
    • Site 83
• Brazil
  • Santo André, Brazil, 09060870
    • Site 45
• Bulgaria
  • Sofia, Bulgaria, 1680
    • Site 28
• Canada
  • Edmonton, Canada, AB T6G 2B7
    • Site 23
  • Ontario
    • Ottawa, Ontario, Canada, K1H 1E4
      • Site 5
• Czechia
  • Hradec Králové, Czechia, 500 05
    • Site 37
  • Prague, Czechia, 150 06
    • Site 39
• France
  • La Tronche, France, 38700
    • Site 46
  • Lille, France, 59037
    • Site 54
  • Marseille, France, 13005
    • Site 65
  • Nice, France, 06202
    • Site 72
  • Paris, France, 75012
    • Site 52
• Germany
  • Berlin, Germany, 12203
    • Site 38
  • Frankfurt, Germany, D-60590
    • Site 44
  • Hanover, Germany, 30625
    • Site 70
• Hong Kong
  • Hong Kong, Hong Kong
    • Site 20
• Hungary
  • Budapest, Hungary, 1088
    • Site 64
• Israel
  • Ashkelon, Israel, 7830604
    • Site 55
  • Haifa, Israel, 3104802
    • Site 49
  • Petah Tikva, Israel, 49100
    • Site 35
  • Petah Tikva, Israel, 4920235
    • Site 34
  • Tel Aviv, Israel, 6423906
    • Site 53
• Italy
  • Milan, Italy, 20138
    • Site 42
  • Milan, Italy, 20157
    • Site 85
  • Monserrato, Italy, 09042
    • Sie 51
  • Monserrato, Italy, CA 09042
    • Site 51
  • Padova, Italy, 35128
    • Site 66
  • San Donato Milanese, Italy, 20097
    • Site 40
  • Torino, Italy, 10128
    • Site 41
• Japan
  • Hiroshima, Japan, 730-8518
    • Site 57
  • Hiroshima, Japan, 734-8551
    • Site 50
  • Kawasaki, Japan, 216-8511
    • Site 58
  • Nagasaki, Japan, 852-8501
    • Site 80
  • Saga, Japan, 849-8501
    • Site 47
  • Tokyo, Japan, 173-0032
    • Site 73
  • Kurume-shi
    • Fukuoka, Kurume-shi, Japan, 830-0011
      • Site 30
  • Mei
    • Tsu, Mei, Japan, 514-8507
      • Site 56
  • Saitama
    • Kawagoe, Saitama, Japan, 350-8550
      • Site 61
  • Soka-shi
    • Saitama, Soka-shi, Japan, 340-0041
      • Site 31
• Netherlands
  • Amsterdam, Netherlands
    • Site 27
• New Zealand
  • Auckland, New Zealand
    • Site 75
• North Macedonia
  • Skopje, North Macedonia, 1000
    • Site 33
• Poland
  • Krakow, Poland, 31-503
    • Site 71
  • Lodz, Poland, 92-213
    • Site 78
  • Rzeszów, Poland, 35-051
    • Site 29
  • Warsaw, Poland, 04-141
    • Site 79
• Portugal
  • Coimbra, Portugal, 3004-561
    • Site 81
  • Lisbon, Portugal, 1649-028
    • Site 82
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Site 59
• South Africa
  • Cape Town, South Africa, 7700
    • Site 21
• South Korea
  • Seongnam-si, South Korea
    • Site 77
  • Jongno
    • Seoul, Jongno, South Korea
      • Site 62
  • Seoul
    • Yangcheon, Seoul, South Korea
      • Site 60
• Spain
  • Barcelona, Spain
    • Site 32
  • Madrid, Spain, 28007
    • Site 63
  • Santa Cruz de Tenerife, Spain, 38010
    • Site 84
  • Seville, Spain, 41013
    • Site 48
  • Valencia, Spain, 46026
    • Site 36
• United Kingdom
  • Bristol, United Kingdom, BS10 5N
    • Site 19
  • Cambridge, United Kingdom, CB2 0QQ
    • Site 16
  • Frimley, United Kingdom, GU16 7UJ
    • Site 22
  • London, United Kingdom, E1 2ES
    • Site 17
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8HD
      • Site 18
  • London
    • Hampstead, London, United Kingdom, NW3 2QG
      • Site 24
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Site 9
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Site 2
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Site 3
  • California
    • San Diego, California, United States, 92122
      • Site 26
    • San Diego, California, United States, 92123,
      • Site 14
    • Santa Monica, California, United States, 90404
      • Site 4
    • Walnut Creek, California, United States, 94598
      • Site 1
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Site 8
    • Colorado Springs, Colorado, United States, 80907
      • Site 11
  • Florida
    • Tampa, Florida, United States, 33613
      • Site 25
    • Weston, Florida, United States, 33331
      • Site 69
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • Site 6
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Site 67
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Site 13
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Site 10
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Site 7
    • Toledo, Ohio, United States, 43617
      • Site 12
  • Pennsylvania
    • Hummelstown, Pennsylvania, United States, 17036
      • Site 15
  • Texas
    • Dallas, Texas, United States, 75231
      • Site 86

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented diagnosis of HAE (Type 1 or 2). The following must be met:

  1. Documented clinical history consistent with HAE
  2. Lab findings consistent with HAE Type 1 or 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:

• 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 3), idiopathic angioedema, or angioedema associated with urticaria.

• Use of therapies prescribed for the prevention of HAE attacks may not be used during the trial or within the below time frames prior to the Run-In Period (adult participants may be on these medications at the time of the Screening Visit, but will need to washout prior to entering the Run-In Period).

  1. Tranexamic acid, oral danazol, oral stanazolol, and oral oxandrolone within 3 days prior to Run-In
  2. Plasma-derived C1INH for LTP within 14 days prior to Run-In
  3. Berotralstat within 21 days prior to Run-In
  4. Lanadelumab within 70 days prior to Run-In
  5. Garadacimab within 90 days prior to Run-In

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (adult); Participants will receive placebo every 3 months.	Drug: Placebo; Placebo will be administered as a subcutaneous injection.
Experimental: Adult Navenibart Dosing Regimen 1; Participants will receive 600 mg of navenibart every 3 months.	Drug: navenibart; Navenibart will be administered as a subcutaneous injection.; Other Names: STAR-0215
Experimental: Adult Navenibart Dosing Regimen 2; Participants will receive 600 mg of navenibart on Day 1 and 300 mg every 3 months starting at month 3.	Drug: navenibart; Navenibart will be administered as a subcutaneous injection.; Other Names: STAR-0215
Experimental: Adult Navenibart Dosing Regimen 3; Participants will receive 600 mg of navenibart every 6 months.	Drug: navenibart; Navenibart will be administered as a subcutaneous injection.; Other Names: STAR-0215
Experimental: Adolescent Navenibart Dosing Regimen 1; Participants will receive 600 mg of navenibart on Day 1 and 300 mg every 3 months starting at month 3.	Drug: navenibart; Navenibart will be administered as a subcutaneous injection.; Other Names: STAR-0215

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of time-normalized investigator-confirmed HAE attacks during the 6-month Treatment Period.	Day 1 through Day 181

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of moderate or severe investigator-confirmed HAE attacks during the 6-month Treatment Period.	Day 1 through Day 181
Number of investigator-confirmed HAE attacks that require on-demand treatment during the 6-month Treatment Period.	Day 1 through Day 181
Percent reduction in monthly investigator-confirmed HAE attacks in the 6-month Treatment Period versus the Run-In Period.	Baseline through Day 181
Time to first investigator-confirmed HAE attack after first and second dose.	Day 1 through Day 181
The number of participants responding to treatment, defined as a ≥ 50%, ≥ 70%, or ≥ 90% reduction from the Run-In Period in investigator-confirmed HAE attack rate (for adult participants: compared to placebo during the 6-month Treatment Period).	Baseline through Day 181
Number of participants with no investigator-confirmed HAE attacks during the 6-month Treatment Period.	Day 1 through Day 181
Change from baseline (Day 1) in the Angioedema Quality of Life questionnaire total score.	Day 1 through Day 181

Other Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events.	Day 1 through Day 361

Collaborators and Investigators

• Sponsor: Astria Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: February 19, 2025
• First Submitted That Met QC Criteria: February 19, 2025
• First Posted (Actual): February 24, 2025

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 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; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: STAR-0215-301

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