Clinical trial NCT04656418: CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks
Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-arm Study to Investigate the Efficacy and Safety of Subcutaneous Administration of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2020-12-07
Enrollment: 64
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a multicenter, double-blind, randomized, placebo-controlled, parallel-arm study to investigate the efficacy and safety of subcutaneous administration of CSL312 (garadacimab) in the prophylactic treatment of hereditary angioedema.


Eligibility criteria: Inclusion Criteria:

* Male or female ≥ 12 years of age; diagnosed with clinically confirmed C1-INH hereditary angioedema; experience ≥ 3 attacks during the 3 months before screening.

Note: For subjects taking any prophylactic HAE therapy during the 3 months before Screening, ≥ 3 HAE attacks may be documented over 3 consecutive months before commencing the prophylactic therapy.

Exclusion Criteria:

* Concomitant diagnosis of another form of angioedema such as idiopathic or acquired angioedema, recurrent angioedema associated with urticarial or hereditary angioedema type 3

Primary outcomes:
measure: Time-Normalized Number of Hereditary Angioedema (HAE) Attacks Per Month During Treatment Period
timeFrame: First injection up to 6 months
Secondary outcomes:
measure: Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period
timeFrame: 6 months, first 3-months and second 3-months of treatment period
measure: Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment
timeFrame: 6 months, first 3-months and second 3-months of treatment period
measure: Time-Normalized Number of Moderate or Severe HAE Attacks Per Month
timeFrame: 6 months, first 3-months and second 3-months of treatment period
measure: Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period
timeFrame: First 3-months and second 3-months of treatment period
measure: Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo
timeFrame: 6 months, first 3-months and second 3-months of treatment period
measure: Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART)
timeFrame: Up to 6 months
measure: Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI)
timeFrame: From first dose of study drug up to 3 months after the last injection (approximately 8 months)
measure: Number of Participants With CSL312-induced Anti-CSL312 Antibodies
timeFrame: Up to 8 months
measure: Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to 3 months after the last injection (approximately 8 months)
measure: Percentage of Participants With at Least One AE, SAE, and AESI
timeFrame: From first dose of study drug up to 3 months after the last injection (approximately 8 months)
measure: Percentage of Participants With CSL312-induced Anti-CSL312 Antibodies
timeFrame: Up to 6 months
measure: Percentage of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs
timeFrame: From first dose of study drug up to 3 months after the last injection (approximately 8 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama
state: Alabama
city: Scottsdale
country: United States
facility: Medical Research of Arizona
state: Arizona
city: Santa Monica
country: United States
facility: Raffi Tachdjian MD, Inc.
state: California
city: Walnut Creek
country: United States
facility: Allergy and Asthma Clinical Research
state: California
city: Chevy Chase
country: United States
facility: Institute of Asthma and Allergy
state: Maryland
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center LLC
state: Ohio
city: Hershey
country: United States
facility: Pennsylvania State University
state: Pennsylvania
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Edmonton
country: Canada
facility: University of Alberta - Research Transition Facility
state: Alberta
city: Ottawa
country: Canada
facility: Ottawa Allergy Research Corp
state: Ontario
city: Toronto
country: Canada
facility: Gordon Sussman Clinical Research Inc.
state: Ontario
city: Québec
country: Canada
facility: Clinique specialisee en allergie de la Capitale
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt Goethe-Universität
state: Hessen
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Mainz
country: Germany
facility: CRC Clinical Research / Hautklinik und Poliklinik der Universitätsklinik Mainz
city: Mörfelden-Walldorf
country: Germany
facility: HZRM Hämophilie Zentrum Rhein Main GmbH
city: Budapest
country: Hungary
facility: Semmelweis University
city: Ashkelon
country: Israel
facility: Barzilai University Medical Center
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima
city: Kobe-shi
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Kawasaki-shi
country: Japan
facility: St.Marianna University School of Medicine Hospital
state: Kanagawa
city: Saitama
country: Japan
facility: Saitama Medical Center
state: Kawagoe-shi
city: Saga
country: Japan
facility: Saga University Hospital
state: Saga-shi
city: Yaizu-shi
country: Japan
facility: Koga Community Hospital
state: Shizuoka
city: Bunkyo
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Saitama
country: Japan
facility: Saiyu Soka Hospital
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Location AMC
Study officials:
affiliation: CSL Behring LLC
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.