CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks

Hereditary Angioedema Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04656418
• Other study ID #: CSL312_3001
• Secondary ID: 2020-000570-25
• Status: Completed
• Phase: Phase 3
• Start date: January 27, 2021
• Est. completion date: June 7, 2022

Study information

• Verified date: June 2023
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: June 7, 2022
• Est. primary completion date: June 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

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

Drug:
• Placebo
Buffer without active ingredient

Locations

Country	Name	City	State
Canada	University of Alberta - Research Transition Facility	Edmonton	Alberta
Canada	Ottawa Allergy Research Corp	Ottawa	Ontario
Canada	Clinique specialisee en allergie de la Capitale	Québec
Canada	Gordon Sussman Clinical Research Inc.	Toronto	Ontario
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Frankfurt Goethe-Universität	Frankfurt	Hessen
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	CRC Clinical Research / Hautklinik und Poliklinik der Universitätsklinik Mainz	Mainz
Germany	HZRM Hämophilie Zentrum Rhein Main GmbH	Mörfelden-Walldorf
Hungary	Semmelweis University	Budapest
Israel	Barzilai University Medical Center	Ashkelon
Japan	Juntendo University Hospital	Bunkyo	Tokyo
Japan	Hiroshima University Hospital	Hiroshima-shi	Hiroshima
Japan	St.Marianna University School of Medicine Hospital	Kawasaki-shi	Kanagawa
Japan	Kobe University Hospital	Kobe-shi	Hyogo
Japan	Saga University Hospital	Saga	Saga-shi
Japan	Saitama Medical Center	Saitama	Kawagoe-shi
Japan	Saiyu Soka Hospital	Saitama
Japan	Koga Community Hospital	Yaizu-shi	Shizuoka
Netherlands	Amsterdam UMC, Location AMC	Amsterdam
United States	Clinical Research Center of Alabama	Birmingham	Alabama
United States	Institute of Asthma and Allergy	Chevy Chase	Maryland
United States	Bernstein Clinical Research Center LLC	Cincinnati	Ohio
United States	AARA Research Center	Dallas	Texas
United States	Pennsylvania State University	Hershey	Pennsylvania
United States	Raffi Tachdjian MD, Inc.	Santa Monica	California
United States	Medical Research of Arizona	Scottsdale	Arizona
United States	Allergy and Asthma Clinical Research	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Hungary,  Israel,  Japan,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time-Normalized Number of Hereditary Angioedema (HAE) Attacks Per Month During Treatment Period	Time-normalized number of HAE attacks per month during treatment was calculated per participant as: [number of HAE attacks / length of participant treatment in days] * 30.4375.	First injection up to 6 months
Secondary	Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period	Percentage change in the time-normalized number of HAE attacks was calculated within a participant as: 100 * [1 - (time-normalized number of HAE attacks per month during treatment period / time-normalized number of HAE attacks per month during run-in period)]. Time-normalized number of HAE attacks per month during treatment period was calculated per participant as: [number of HAE attacks / length of participant treatment in days] * 30.4375.	6 months, first 3-months and second 3-months of treatment period
Secondary	Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment	Time-normalized number of HAE attacks per month requiring on-demand treatment was calculated per participant as: [number of HAE attacks requiring on-demand treatment / length of participant in days] * 30.4375.	6 months, first 3-months and second 3-months of treatment period
Secondary	Time-Normalized Number of Moderate or Severe HAE Attacks Per Month	Time-normalized number of moderate or severe HAE attacks per month during treatment period was calculated per participant as: [number of moderate or severe HAE attacks / length of participant treatment in days] * 30.4375.	6 months, first 3-months and second 3-months of treatment period
Secondary	Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period	Time-normalized number of HAE attacks per month during treatment was calculated per participant as: [number of HAE attacks / length of participant treatment in days] * 30.4375.	First 3-months and second 3-months of treatment period
Secondary	Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo	Relative difference in means in the time-normalized number of HAE attacks per month CSL312 to Placebo was calculated as: 100 * [(mean time-normalized number of HAE attacks for CSL312 - mean time-normalized number of HAE attacks for placebo) / mean time-normalized number of HAE attacks for placebo]. Time-normalized number of HAE attacks per month during treatment was calculated per participant as: [number of HAE attacks / length of participant treatment in days] * 30.4375.	6 months, first 3-months and second 3-months of treatment period
Secondary	Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART)	SGART is a self-assessment by the participant and measures the subject's overall treatment response to the investigational product using the following ratings: 0 (none: worse or no response at all, not acceptable), 1 (poor: very little response, not acceptable), 2 (fair: some response, acceptable but could be better), 3 (good: good response, acceptable), and 4 (excellent: excellent response, as good as can be imagined).	Up to 6 months
Secondary	Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI)	AE is any untoward medical occurrence in a participant administered with an investigational product which does not necessarily have a causal relationship with treatment, can be any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product, whether or not considered related to product. SAE is any untoward medical occurrence that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event. An AESI is an AE of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor is appropriate.	From first dose of study drug up to 3 months after the last injection (approximately 8 months)
Secondary	Number of Participants With CSL312-induced Anti-CSL312 Antibodies		Up to 8 months
Secondary	Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs)	Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters.	From first dose of study drug up to 3 months after the last injection (approximately 8 months)
Secondary	Percentage of Participants With at Least One AE, SAE, and AESI	AE is any untoward medical occurrence in a participant administered with an investigational product which does not necessarily have a causal relationship with treatment, can be any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product, whether or not considered related to product. SAE is any untoward medical occurrence that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event. An AESI is an AE of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor is appropriate.	From first dose of study drug up to 3 months after the last injection (approximately 8 months)
Secondary	Percentage of Participants With CSL312-induced Anti-CSL312 Antibodies		Up to 6 months
Secondary	Percentage of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs	Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters.	From first dose of study drug up to 3 months after the last injection (approximately 8 months)