CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks

Phase 3

Completed

• Conditions: Hereditary Angioedema
• Interventions: Biological: CSL312; Drug: Placebo

• Registration Number: NCT04656418
• Lead Sponsor: CSL Behring

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-12-01
• Study First Submitted QC: 2020-12-01
• Study First Posted: 2020-12-07
• Study Start: 2021-01-27
• Primary Completion: 2022-06-07
• Study Completion: 2022-06-07
• Status Verified: 2023-06
• Results First Submitted: 2023-06-07
• Results First Submitted QC: 2023-06-07
• Last Update Submitted: 2023-06-07
• Results First Posted: 2023-06-29
• Last Update Posted: 2023-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CSL312	CSL312	Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg subcutaneous (SC) injections, once monthly from Months 2 to 6.
Placebo	Placebo	Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.

Primary Outcome Measures

Name	Time	Method
Time-Normalized Number of Hereditary Angioedema (HAE) Attacks Per Month During Treatment Period	First injection up to 6 months	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.

Secondary Outcome Measures

Name	Time	Method
Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment	6 months, first 3-months and second 3-months of treatment period	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.
Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs)	From first dose of study drug up to 3 months after the last injection (approximately 8 months)	Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters.
Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period	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.
Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI)	From first dose of study drug up to 3 months after the last injection (approximately 8 months)	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.
Number of Participants With CSL312-induced Anti-CSL312 Antibodies	Up to 8 months
Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period	6 months, first 3-months and second 3-months of treatment 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.
Time-Normalized Number of Moderate or Severe HAE Attacks Per Month	6 months, first 3-months and second 3-months of treatment period	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.
Percentage of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs	From first dose of study drug up to 3 months after the last injection (approximately 8 months)	Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters.
Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo	6 months, first 3-months and second 3-months of treatment period	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.
Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART)	Up to 6 months	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).
Percentage of Participants With at Least One AE, SAE, and AESI	From first dose of study drug up to 3 months after the last injection (approximately 8 months)	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.
Percentage of Participants With CSL312-induced Anti-CSL312 Antibodies	Up to 6 months

Trial Locations

Locations (28)

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

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

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

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

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

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

Pennsylvania State University; 🇺🇸 Hershey, Pennsylvania, United States

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

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

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

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

Clinique specialisee en allergie de la Capitale; 🇨🇦 Québec, Canada

Charité Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Universitätsklinikum Leipzig; 🇩🇪 Leipzig, Germany

CRC Clinical Research / Hautklinik und Poliklinik der Universitätsklinik Mainz; 🇩🇪 Mainz, Germany

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

Barzilai University Medical Center; 🇮🇱 Ashkelon, Israel

Kobe University Hospital; 🇯🇵 Kobe-shi, Hyogo, Japan

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

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

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

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

Juntendo University Hospital; 🇯🇵 Bunkyo, Tokyo, Japan

Saiyu Soka Hospital; 🇯🇵 Saitama, Japan

Amsterdam UMC, Location AMC; 🇳🇱 Amsterdam, Netherlands

Universitätsklinikum Frankfurt Goethe-Universität; 🇩🇪 Frankfurt, Hessen, Germany

Hiroshima University Hospital; 🇯🇵 Hiroshima-shi, Hiroshima, Japan

Semmelweis University; 🇭🇺 Budapest, Hungary