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

Hereditary Angioedema Clinical Trial

Official title:

An Open-label Study to Evaluate the Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04739059
• Other study ID #: CSL312_3002
• Secondary ID: 2020-003918-12
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 29, 2021
• Est. completion date: November 2025

Study information

• Verified date: June 2024
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 171
• Est. completion date: November 2025
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Biological:
• CSL312
Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody

Locations

Country	Name	City	State
Australia	Campbelltown Hospital / Western Sydney University	Campbelltown	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital, Department of Clinical Immunology	Murdoch	West Australia
Canada	University of Alberta - Research Transition Facility	Edmonton	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	Montreal Clinical Research Institute	Montréal	Quebec
Canada	Ottawa Allergy Research Corp	Ottawa	Ontario
Canada	Gordon Sussman Clinical Research	Toronto	Ontario
Czechia	University hospital St. Anna Ustav klinicke imunologie a alergologie, Fakultní nemocnice u sv. Anny v Brne	Brno
Czechia	University Hospital Motol	Praha 5
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Johannes Gutenberg-Universität KöR, Hautklinik und Poliklinik der Universitätsmedizin, Clinical Research Center	Mainz
Germany	HZRM Haemophilie Zentrum Rhein Main GmbH	Mörfelden-Walldorf
Hong Kong	The University of Hong Kong, Queen Mary Hospital	Hong Kong
Hungary	Semmelweis Egyetem Altalanos Orvostudományi Kar Belgyógyászati és Hematológiai Klinika	Budapest
Israel	Barzilai University Medical Center	Ashkelon
Japan	Clover Hospital	Kanagawa	Kugenumaishigami, Fujisawa-shi
Japan	St. Marianna University School of Medicine Hospital	Kanagawa	Kawasaki-shi
Japan	Mie University Hospital	Mie	Edobashi, Tsu-shi
Japan	Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital	Miyakojima-ku	Osaka-shi
Japan	Saga University Hospital	Saga	Nebeshima, Saga-shi
Japan	Saitama Medical Center	Saitama	Kamoda Kawagoe-shi
Japan	Saiyu Soka Hospital	Saitama	Matsubara Soka-shi
Japan	Koga Community Hospital	Shizuoka	Daikakuji Yaizu-shi
Japan	Juntendo University Hospital	Tokyo	Hongo Bunkyo-ku
Japan	National Hospital Organization Disaster Medical Center	Tokyo	Midoricho, Tachikawa-shi
Netherlands	Amsterdam UMC, location AMC	Amsterdam
New Zealand	Auckland City Hospital	Grafton	Auckland
Russian Federation	NRC Institute of Immunology FMBA Russia	Moscow
Spain	Hospital Universitari General de La Vall d'Hebron	Barcelona
Spain	Hospital Gregorio Marañón, Servicio de Alergia	Madrid
Taiwan	Taichung Veterans General Hospital	Taichung City
United States	Clinical Research Center of Alabama	Birmingham	Alabama
United States	Institute for Asthma and Allergy PC	Chevy Chase	Maryland
United States	Bernstein Clinical Research Center, LLC	Cincinnati	Ohio
United States	AARA Research Center	Dallas	Texas
United States	PennState Health Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Research Solutions of Arizona	Litchfield Park	Arizona
United States	Little Rock Allergy & Asthma Clinic	Little Rock	Arkansas
United States	Donald S. Levy M.D.	Orange	California
United States	Raffi Tachdjian MD, Inc.	Santa Monica	California
United States	Medical Research of Arizona	Scottsdale	Arizona
United States	Allergy & Asthma Clinical Research	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Germany,  Hong Kong,  Hungary,  Israel,  Japan,  Netherlands,  New Zealand,  Russian Federation,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with treatment emergent adverse events (TEAEs)		Up to 45 months
Primary	Percentage of subjects with TEAEs		Up to 45 months
Primary	TEAEs rates per injection		Up to 45 months
Primary	TEAEs rates per subject year		Up to 45 months
Secondary	The time-normalized number (per month and year) of Hereditary Angioedema (HAE attacks) for the entire study		Up to 43 months
Secondary	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
Secondary	The time-normalized number (per month and year) of HAE attacks requiring on-demand treatment in subjects on treatment		Up to 43 months
Secondary	The time-normalized number (per month and year) of moderate and/or severe HAE attacks in subjects on treatment		Up to 43 months
Secondary	Number and percentage of subjects rating their response to therapy as good or excellent		Up to 43 months
Secondary	The number and percentage of subjects experiencing TEAEs		Up to 45 months
Secondary	The number and percentage of subjects experiencing adverse events of special interest (AESIs)		Up to 45 months
Secondary	The number and percentage of subjects experiencing serious adverse events (SAEs), including deaths		Up to 45 months
Secondary	The number and percentage of subjects experiencing CSL312 induced anti-CSL312 antibodies		Up to 45 months