Safety Study in Subjects ≥ 12 Years of Age With Hereditary Angioedema Switching to Garadacimab

A Phase 4 Open-label Study to Evaluate the Safety After Switching to CSL312 (Garadacimab) From Current Prophylactic HAE Treatment in Subjects With HAE ≥ 12 Years of Age

This study is designed to evaluate the safety after switching to garadacimab from another prophylactic hereditary angioedema (HAE) treatment (marketed kallikrein [KK] inhibitor or plasma-derived C1-esterase inhibitor [pdC1INH]prophylactic) when administered once monthly for approximately 3 months in participants aged greater than or equal to (>=) 12 years with HAE.

Study Overview

• Status: Active, not recruiting
• Conditions: Hereditary Angioedema
• Intervention / Treatment: Biological: Garadacimab

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4W2
    • Clinique Spécialisée en Allergie de la Capitale
  • Ontario
    • Hamilton, Ontario, Canada, ON L8N3Z5
      • McMaster University-Hamilton
  • Quebec
    • Montreal, Quebec, Canada, QC H2W 1R7
      • Montreal Clinical Research Institute
• Germany
  • Frankfurt, Germany, 60596
    • HZRM Hämophilie Zentrum Rhein Main GmbH
  • Mainz, Germany, 55131
    • Hautklinik und Poliklinik der Universitätsklinik Mainz
• United States
  • Arizona
    • Litchfield Park, Arizona, United States, 85340
      • Research Solutions of Arizona
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Allergy and Asthma Clinic of Northwest Arkansas
  • California
    • Orange, California, United States, 92868
      • Donald Levy M.D.
    • Santa Monica, California, United States, 90404
      • Raffi Tachdjian MD, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Bernstein Clinical Research Center, LLC
  • Utah
    • West Valley City, Utah, United States, 84119
      • Chronicle Bio

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• • Aged >= 12 years at the time of providing written informed consent / assent.
• • Have a history of response to on-demand HAE treatment for the treatment of acute HAE attacks.
• • Documented laboratory diagnosis in medical records of C1-esterase inhibitor hereditary angioedema (HAE-C1INH) type 1 or type 2:
• ◦ Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria),
• ◦ C1-esterase inhibitor (C1INH) antigen concentration or functional activity less than (<) 50% of normal as documented in the participant's medical record, or
• ◦ C4-antigen concentration below the lower limit of the reference range as documented in the participant's medical record.
• For HAE-nC1INH: Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria); an HAE-associated FXII gene mutation (eg, FXII point mutation Thr328Lys or Thr328Arg, or deletion of 72 base pairs [c.971_1018 + 24del72], or duplication of 18 base pairs [c.892-909dup]), as documented in the participant's medical record, OR an HAE-associated plasminogen gene mutation (PLG) gene mutation (eg, PLG point mutation Lys330Glu), as documented in the participant's medical record; C1INH antigen concentration or functional activity 70 to 120% of the normal level, as documented in the participant's medical record.
• • Use of lanadelumab, berotralstat, or pdC1INH for the prophylactic treatment of HAE and be on a stable (consistent) dose / regimen of such medication for at least 3 months prior to Screening.

Exclusion Criteria:

• • Concomitant diagnosis of another form of angioedema, such as idiopathic or acquired angioedema or recurrent angioedema associated with urticaria.
• • Use of androgens, antifibrinolytics, or investigational products (other than garadacimab) for routine prophylaxis against HAE attacks.
• • Known or suspected hypersensitivity to monoclonal antibody therapy or hypersensitivity to the active substance (garadacimab) or to any of the excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Garadacimab

Biological: Garadacimab; Participants will receive a loading dose of garadacimab, followed by once monthly garadacimab administration for 2 months. Garadacimab will be given as a subcutaneous injection. The timing for the administration of the loading dose (first administration of garadacimab) is determined by the dosing schedule of the current HAE prophylactic treatment. No washout necessary.; Other Names: CSL312 and Factor XIIa inhibitor monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Up to Day 95 (End of study [EoS])
Percentage of Participants With TEAEs	Up to Day 95 (EoS)
Number of TEAEs	Up to Day 95 (EoS)
Rate of TEAEs per injection	Up to Day 95 (EoS)
Rate of TEAEs per participant year	Up to Day 95 (EoS)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With: Serious Adverse Events (SAEs), Deaths, Related TEAEs, TEAEs leading to study discontinuation, TEAEs by severity, Laboratory Findings Reported as an AE, and Adverse Events of Special Interest (AESI)	The AESIs for garadacimab are severe hypersensitivity including anaphylaxis.	Up to Day 95 (EoS)
Percentage of Participants With: SAEs, Deaths, Treatment Related TEAEs, TEAEs leading to study discontinuation, TEAEs by severity, Laboratory Findings Reported as an AE, and AESI		Up to Day 95 (EoS)
Number of SAEs, Deaths, Treatment Related TEAEs, TEAEs leading to study discontinuation, TEAEs by severity, AESI and Laboratory Findings Reported as an AE, and AESI		Up to Day 95 (EoS)
Rate per injection of: SAEs, Deaths, Treatment Related TEAEs, TEAEs leading to study discontinuation, TEAEs by severity, Laboratory Findings Reported as an AE, and AESI		Up to Day 95 (EoS)
Rate per participant year of: SAEs, Deaths, Treatment Related TEAEs, TEAEs leading to study discontinuation, TEAEs by severity, Laboratory Findings Reported as an AE, and AESI		Up to Day 95 (EoS)
Number of Participants with Anti-garadacimab Antibodies		Up to Day 95 (EoS)
Percentage of Participants with Anti-garadacimab Antibodies		Up to Day 95 (EoS)
Plasma Concentrations of Garadacimab		Up to Day 95 (EoS)
Percentage of Participants who Indicated Their Preference for Garadacimab		Up to Day 95 (EoS)

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2025
• Primary Completion (Estimated): June 23, 2026
• Study Completion (Estimated): June 23, 2026

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: February 3, 2025
• First Posted (Actual): February 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Monoclonal antibody; Autosomal dominant disease; Hereditary angioedema attack
• 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; Immunologic Factors; Physiological Effects of Drugs; Antibodies, Monoclonal
• Other Study ID Numbers: CSL312_4002; 2024-517757-27-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (i.e. FDA, EMA) is complete and the primary publication is available

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No