Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema Attacks

NCT04739059 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: CSL312_30022020-003918-12
• Study Type: interventional
• Target: 171
• Locations: 14 countries
• Sites: 44

Brief Summary

This phase 3b study will evaluate long-term safety and efficacy of CSL312 (also known as garadacimab) when administered subcutaneously (SC)

Conditions

Hereditary Angioedema

Outcome Measures

Primary Outcomes (4)

• Number of subjects with treatment emergent adverse events (TEAEs)

  Up to 45 months

• Percentage of subjects with TEAEs

  Up to 45 months

• TEAEs rates per injection

  Up to 45 months

• TEAEs rates per subject year

  Up to 45 months

Secondary Outcomes (9)

• The time-normalized number (per month and year) of Hereditary Angioedema (HAE attacks) for the entire study

  Up to 43 months

• The percentage reduction and the number of subjects experiencing at least ≥ 50% ≥ 70%, ≥ 90 or equal to 100% (attack free) reduction in the time-normalized number of HAE attacks on Treatment compared to Run-in Period

  Up to 43 months

• The time-normalized number (per month and year) of HAE attacks requiring on-demand treatment in subjects on treatment

  Up to 43 months

• The time-normalized number (per month and year) of moderate and/or severe HAE attacks in subjects on treatment

  Up to 43 months

• Number and percentage of subjects rating their response to therapy as good or excellent

  Up to 43 months

Study Arms (1)

CSL312

EXPERIMENTAL

Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody administered subcutaneously

Biological: CSL312

Interventions

CSL312 BIOLOGICAL

Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody

Also known as: Factor XIIa inhibitor monoclonal antibody, garadacimab

CSL312

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:

• \- Males and females aged ≥ 12 years
• \- Diagnosed with clinically confirmed C1-INH HAE
• \- Experienced ≥ 3 HAE attacks during the 3 months before Screening
• \- Participated in the Run-in Period for at least 1 month (CSL312-naïve subjects only)
• \- Experienced at least an average of 1 HAE attack per month during the Run-in Period

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 C1-INH products, androgens, antifibrinolytics or other small molecule medications for routine prophylaxis against HAE attacks at least 2 weeks before the first day of the Run-in Period
• \- Use of monoclonal antibodies such as lanadelumab (Takhzyro®) 3 months before the first day of the Run-in Period.
• \- Female subjects use estrogen-containing oral contraceptives or hormone replacement therapy within 4 weeks prior to screening
• \- Female or male subjects who are fertile and sexually active not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 30 days after receipt of the last dose of CSL312
• \- Pregnant, breastfeeding, or not willing to cease breastfeeding

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (44)

Clinical Research Center of Alabama

Birmingham, Alabama, 35209, United States

Location

Research Solutions of Arizona

Litchfield Park, Arizona, 85340, United States

Location

Medical Research of Arizona

Scottsdale, Arizona, 85251, United States

Location

Little Rock Allergy & Asthma Clinic

Little Rock, Arkansas, 72205, United States

Location

Donald S. Levy M.D.

Orange, California, 92868, United States

Location

Raffi Tachdjian MD, Inc.

Santa Monica, California, 90404, United States

Location

Allergy & Asthma Clinical Research

Walnut Creek, California, 94598, United States

Location

Institute for Asthma and Allergy PC

Chevy Chase, Maryland, 20815, United States

Location

Bernstein Clinical Research Center, LLC

Cincinnati, Ohio, 45236, United States

Location

PennState Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

AARA Research Center

Dallas, Texas, 75231, United States

Location

Campbelltown Hospital / Western Sydney University

Campbelltown, New South Wales, 2560, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Fiona Stanley Hospital, Department of Clinical Immunology

Murdoch, Western Australia, 6150, Australia

Location

University of Alberta - Research Transition Facility

Edmonton, Alberta, T6G 2B7, Canada

Location

McMaster University

Hamilton, Ontario, L8N 3Z5, Canada

Location

Ottawa Allergy Research Corp

Ottawa, Ontario, K1H 1E4, Canada

Location

Gordon Sussman Clinical Research

Toronto, Ontario, M3B 3S6, Canada

Location

Montreal Clinical Research Institute

Montreal, Quebec, H2W 1R7, Canada

Location

University hospital St. Anna Ustav klinicke imunologie a alergologie, Fakultní nemocnice u sv. Anny v Brně

Brno, 65691, Czechia

Location

University Hospital Motol

Prague, 150 06, Czechia

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Johannes Gutenberg-Universität KöR, Hautklinik und Poliklinik der Universitätsmedizin, Clinical Research Center

Mainz, 55131, Germany

Location

HZRM Haemophilie Zentrum Rhein Main GmbH

Mörfelden-Walldorf, 64546, Germany

Location

The University of Hong Kong, Queen Mary Hospital

Hong Kong, Hong Kong

Location

Semmelweis Egyetem Altalanos Orvostudományi Kar Belgyógyászati és Hematológiai Klinika

Budapest, 1088, Hungary

Location

Barzilai University Medical Center

Ashkelon, 7830604, Israel

Location

Koga Community Hospital

Shizuoka, Daikakuji Yaizu-shi, 425-0088, Japan

Location

Mie University Hospital

Mie, Edobashi, Tsu-shi, Edobashi, Tsu-shi, Japan

Location

Juntendo University Hospital

Tokyo, Hongo Bunkyo-ku, 113-8431, Japan

Location

Saitama Medical Center

Saitama, Kamoda Kawagoe-shi, 350-8550, Japan

Location

St. Marianna University School of Medicine Hospital

Kanagawa, Kawasaki-shi, 216-8511, Japan

Location

Clover Hospital

Kanagawa, Kugenumaishigami, Fujisawa-shi, 251-0025, Japan

Location

Saiyu Soka Hospital

Saitama, Matsubara Soka-shi, 340-0041, Japan

Location

National Hospital Organization Disaster Medical Center

Tokyo, Midoricho, Tachikawa-shi, 190-0014, Japan

Location

Saga University Hospital

Saga, Nebeshima, Saga-shi, 849-8501, Japan

Location

Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital

Miyakojima-ku, Osaka-shi, 534-0021, Japan

Location

Amsterdam UMC, location AMC

Amsterdam, 1105, Netherlands

Location

Auckland City Hospital

Grafton, Auckland, 1023, New Zealand

Location

NRC Institute of Immunology FMBA Russia

Moscow, 115522, Russia

Location

Hospital Universitari General de La Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Gregorio Marañón, Servicio de Alergia

Madrid, 28007, Spain

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

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 3
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: February 4, 2021
• Study Start: April 29, 2021
• Primary Completion: November 21, 2025
• Study Completion: November 21, 2025
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.
• Access Criteria: Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee. An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee. The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

Locations

DE (4); RU (1); US (11); HK (1); AU (3); CA (5); NL (1); ES (2); CZ (2); TW (1); NZ (1); JP (10); HU (1); IL (1)