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

NCT06806657 | Completed Phase 4 FDA Drug

• 2 other identifiers: CSL312_40022024-517757-27-00
• Study Type: interventional
• Target: 18
• Locations: 3 countries
• Sites: 11

Brief Summary

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.

Conditions

Hereditary Angioedema

Keywords

Autosomal dominant disease; Hereditary angioedema attack; Monoclonal antibody

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (9)

• 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)

  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)

Study Arms (1)

Garadacimab

EXPERIMENTAL

Biological: Garadacimab

Interventions

Garadacimab BIOLOGICAL

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.

Also known as: CSL312 and Factor XIIa inhibitor monoclonal antibody

Garadacimab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (11)

Research Solutions of Arizona

Litchfield Park, Arizona, 85340, United States

Location

Allergy and Asthma Clinic of Northwest Arkansas

Bentonville, Arkansas, 72712, United States

Location

Donald Levy M.D.

Orange, California, 92868, United States

Location

Raffi Tachdjian MD, Inc.

Santa Monica, California, 90404, United States

Location

Bernstein Clinical Research Center, LLC

Cincinnati, Ohio, 45236, United States

Location

Chronicle Bio

West Valley City, Utah, 84119, United States

Location

McMaster University-Hamilton

Hamilton, Ontario, ON L8N3Z5, Canada

Location

Montreal Clinical Research Institute

Montreal, Quebec, QC H2W 1R7, Canada

Location

Clinique Spécialisée en Allergie de la Capitale

Québec, G1V 4W2, Canada

Location

HZRM Hämophilie Zentrum Rhein Main GmbH

Frankfurt, 60596, Germany

Location

Hautklinik und Poliklinik der Universitätsklinik Mainz

Mainz, 55131, Germany

Location

MeSH Terms

Conditions

Angioedemas, Hereditary

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Study Officials

• Study Director

  CSL Behring

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 4, 2025
• Study Start: April 28, 2025
• Primary Completion: June 29, 2026
• Study Completion: June 29, 2026
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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
• 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.

Locations

US (6); CA (3); DE (2)