Clinical trial NCT04739059: Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema Attacks
Official title: An Open-label Study to Evaluate the Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hereditary Angioedema
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2021-02-04
Enrollment: 171
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of subjects with treatment emergent adverse events (TEAEs)
timeFrame: Up to 45 months
measure: Percentage of subjects with TEAEs
timeFrame: Up to 45 months
measure: TEAEs rates per injection
timeFrame: Up to 45 months
measure: TEAEs rates per subject year
timeFrame: Up to 45 months
Secondary outcomes:
measure: The time-normalized number (per month and year) of Hereditary Angioedema (HAE attacks) for the entire study
timeFrame: Up to 43 months
measure: 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
timeFrame: Up to 43 months
measure: The time-normalized number (per month and year) of HAE attacks requiring on-demand treatment in subjects on treatment
timeFrame: Up to 43 months
measure: The time-normalized number (per month and year) of moderate and/or severe HAE attacks in subjects on treatment
timeFrame: Up to 43 months
measure: Number and percentage of subjects rating their response to therapy as good or excellent
timeFrame: Up to 43 months
measure: The number and percentage of subjects experiencing TEAEs
timeFrame: Up to 45 months
measure: The number and percentage of subjects experiencing adverse events of special interest (AESIs)
timeFrame: Up to 45 months
measure: The number and percentage of subjects experiencing serious adverse events (SAEs), including deaths
timeFrame: Up to 45 months
measure: The number and percentage of subjects experiencing CSL312 induced anti-CSL312 antibodies
timeFrame: Up to 45 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama
state: Alabama
city: Litchfield Park
country: United States
facility: Research Solutions of Arizona
state: Arizona
city: Scottsdale
country: United States
facility: Medical Research of Arizona
state: Arizona
city: Little Rock
country: United States
facility: Little Rock Allergy & Asthma Clinic
state: Arkansas
city: Orange
country: United States
facility: Donald S. Levy M.D.
state: California
city: Santa Monica
country: United States
facility: Raffi Tachdjian MD, Inc.
state: California
city: Walnut Creek
country: United States
facility: Allergy & Asthma Clinical Research
state: California
city: Chevy Chase
country: United States
facility: Institute for Asthma and Allergy PC
state: Maryland
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center, LLC
state: Ohio
city: Hershey
country: United States
facility: PennState Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Campbelltown
country: Australia
facility: Campbelltown Hospital / Western Sydney University
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital, Department of Clinical Immunology
state: West Australia
city: Edmonton
country: Canada
facility: University of Alberta - Research Transition Facility
state: Alberta
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Allergy Research Corp
state: Ontario
city: Toronto
country: Canada
facility: Gordon Sussman Clinical Research
state: Ontario
city: Montréal
country: Canada
facility: Montreal Clinical Research Institute
state: Quebec
city: Brno
country: Czechia
facility: University hospital St. Anna Ustav klinicke imunologie a alergologie, Fakultní nemocnice u sv. Anny v Brně
city: Praha 5
country: Czechia
facility: University Hospital Motol
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universität KöR, Hautklinik und Poliklinik der Universitätsmedizin, Clinical Research Center
city: Mörfelden-Walldorf
country: Germany
facility: HZRM Haemophilie Zentrum Rhein Main GmbH
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong, Queen Mary Hospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Altalanos Orvostudományi Kar Belgyógyászati és Hematológiai Klinika
city: Ashkelon
country: Israel
facility: Barzilai University Medical Center
city: Shizuoka
country: Japan
facility: Koga Community Hospital
state: Daikakuji Yaizu-shi
city: Mie
country: Japan
facility: Mie University Hospital
state: Edobashi, Tsu-shi
city: Tokyo
country: Japan
facility: Juntendo University Hospital
state: Hongo Bunkyo-ku
city: Saitama
country: Japan
facility: Saitama Medical Center
state: Kamoda Kawagoe-shi
city: Kanagawa
country: Japan
facility: St. Marianna University School of Medicine Hospital
state: Kawasaki-shi
city: Kanagawa
country: Japan
facility: Clover Hospital
state: Kugenumaishigami, Fujisawa-shi
city: Saitama
country: Japan
facility: Saiyu Soka Hospital
state: Matsubara Soka-shi
city: Tokyo
country: Japan
facility: National Hospital Organization Disaster Medical Center
state: Midoricho, Tachikawa-shi
city: Saga
country: Japan
facility: Saga University Hospital
state: Nebeshima, Saga-shi
city: Miyakojima-ku
country: Japan
facility: Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital
state: Osaka-shi
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location AMC
city: Grafton
country: New Zealand
facility: Auckland City Hospital
state: Auckland
city: Moscow
country: Russian Federation
facility: NRC Institute of Immunology FMBA Russia
city: Barcelona
country: Spain
facility: Hospital Universitari General de La Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón, Servicio de Alergia
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hospital
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: