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

Phase 3

Active, not recruiting

• Conditions: Hereditary Angioedema
• Interventions: Biological: CSL312

• Registration Number: NCT04739059
• Lead Sponsor: CSL Behring

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-01
• Study First Submitted QC: 2021-02-01
• Study First Posted: 2021-02-04
• Study Start: 2021-03-29
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-08
• Last Update Posted: 2025-01-09
• Primary Completion: 2025-11
• Study Completion: 2025-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 171

Inclusion Criteria

• 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

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Exclusion Criteria

• 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CSL312	CSL312	Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody administered subcutaneously

Primary Outcome Measures

Name	Time	Method
Number of subjects with treatment emergent adverse events (TEAEs)	Up to 45 months
TEAEs rates per subject year	Up to 45 months
TEAEs rates per injection	Up to 45 months
Percentage of subjects with TEAEs	Up to 45 months

Secondary Outcome Measures

Name	Time	Method
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
The time-normalized number (per month and year) of Hereditary Angioedema (HAE attacks) for the entire study	Up to 43 months
The number and percentage of subjects experiencing CSL312 induced anti-CSL312 antibodies	Up to 45 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 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 number and percentage of subjects experiencing serious adverse events (SAEs), including deaths	Up to 45 months
The number and percentage of subjects experiencing TEAEs	Up to 45 months
The number and percentage of subjects experiencing adverse events of special interest (AESIs)	Up to 45 months

Trial Locations

Locations (44)

Gordon Sussman Clinical Research; 🇨🇦 Toronto, Ontario, Canada

Semmelweis Egyetem Altalanos Orvostudományi Kar Belgyógyászati és Hematológiai Klinika; 🇭🇺 Budapest, Hungary

McMaster University; 🇨🇦 Hamilton, Ontario, Canada

Clinical Research Center of Alabama; 🇺🇸 Birmingham, Alabama, United States

Donald S. Levy M.D.; 🇺🇸 Orange, California, United States

Medical Research of Arizona; 🇺🇸 Scottsdale, Arizona, United States

Little Rock Allergy & Asthma Clinic; 🇺🇸 Little Rock, Arkansas, United States

PennState Health Milton S. Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

AARA Research Center; 🇺🇸 Dallas, Texas, United States

Fiona Stanley Hospital, Department of Clinical Immunology; 🇦🇺 Murdoch, West Australia, Australia

Ottawa Allergy Research Corp; 🇨🇦 Ottawa, Ontario, Canada

Montreal Clinical Research Institute; 🇨🇦 Montréal, Quebec, Canada

University hospital St. Anna Ustav klinicke imunologie a alergologie, Fakultní nemocnice u sv. Anny v Brně; 🇨🇿 Brno, Czechia

University Hospital Motol; 🇨🇿 Praha 5, Czechia

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Johannes Gutenberg-Universität KöR, Hautklinik und Poliklinik der Universitätsmedizin, Clinical Research Center; 🇩🇪 Mainz, Germany

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt, Germany

The University of Hong Kong, Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong

HZRM Haemophilie Zentrum Rhein Main GmbH; 🇩🇪 Mörfelden-Walldorf, Germany

Barzilai University Medical Center; 🇮🇱 Ashkelon, Israel

Koga Community Hospital; 🇯🇵 Shizuoka, Daikakuji Yaizu-shi, Japan

Juntendo University Hospital; 🇯🇵 Tokyo, Hongo Bunkyo-ku, Japan

St. Marianna University School of Medicine Hospital; 🇯🇵 Kanagawa, Kawasaki-shi, Japan

Clover Hospital; 🇯🇵 Kanagawa, Kugenumaishigami, Fujisawa-shi, Japan

Saitama Medical Center; 🇯🇵 Saitama, Kamoda Kawagoe-shi, Japan

National Hospital Organization Disaster Medical Center; 🇯🇵 Tokyo, Midoricho, Tachikawa-shi, Japan

Saiyu Soka Hospital; 🇯🇵 Saitama, Matsubara Soka-shi, Japan

Saga University Hospital; 🇯🇵 Saga, Nebeshima, Saga-shi, Japan

Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital; 🇯🇵 Miyakojima-ku, Osaka-shi, Japan

NRC Institute of Immunology FMBA Russia; 🇷🇺 Moscow, Russian Federation

Amsterdam UMC, location AMC; 🇳🇱 Amsterdam, Netherlands

Hospital Universitari General de La Vall d'Hebron; 🇪🇸 Barcelona, Spain

Taichung Veterans General Hospital; 🇨🇳 Taichung City, Taiwan

Hospital Gregorio Marañón, Servicio de Alergia; 🇪🇸 Madrid, Spain

Bernstein Clinical Research Center, LLC; 🇺🇸 Cincinnati, Ohio, United States

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Institute for Asthma and Allergy PC; 🇺🇸 Chevy Chase, Maryland, United States

University of Alberta - Research Transition Facility; 🇨🇦 Edmonton, Alberta, Canada

Raffi Tachdjian MD, Inc.; 🇺🇸 Santa Monica, California, United States

Campbelltown Hospital / Western Sydney University; 🇦🇺 Campbelltown, New South Wales, Australia

Mie University Hospital; 🇯🇵 Mie, Edobashi, Tsu-shi, Japan

Auckland City Hospital; 🇳🇿 Grafton, Auckland, New Zealand

Research Solutions of Arizona; 🇺🇸 Litchfield Park, Arizona, United States

Allergy & Asthma Clinical Research; 🇺🇸 Walnut Creek, California, United States