Back to resultsCSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks
Primary Purpose
Hereditary Angioedema
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
CSL312
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for 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
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
Sites / Locations
- Clinical Research Center of Alabama
- Medical Research of Arizona
- Raffi Tachdjian MD, Inc.
- Allergy and Asthma Clinical Research
- Institute of Asthma and Allergy
- Bernstein Clinical Research Center LLC
- Pennsylvania State University
- AARA Research Center
- University of Alberta - Research Transition Facility
- Ottawa Allergy Research Corp
- Gordon Sussman Clinical Research Inc.
- Clinique specialisee en allergie de la Capitale
- Universitätsklinikum Frankfurt Goethe-Universität
- Charité Universitätsmedizin Berlin
- Universitätsklinikum Leipzig
- CRC Clinical Research / Hautklinik und Poliklinik der Universitätsklinik Mainz
- HZRM Hämophilie Zentrum Rhein Main GmbH
- Semmelweis University
- Barzilai University Medical Center
- Hiroshima University Hospital
- Kobe University Hospital
- St.Marianna University School of Medicine Hospital
- Saitama Medical Center
- Saga University Hospital
- Koga Community Hospital
- Juntendo University Hospital
- Saiyu Soka Hospital
- Amsterdam UMC, Location AMC
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
CSL312
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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).
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.
Number of Participants With CSL312-induced Anti-CSL312 Antibodies
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.
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.
Percentage of Participants With CSL312-induced Anti-CSL312 Antibodies
Percentage of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs
Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04656418
Brief Title
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
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
January 27, 2021 (Actual)
Primary Completion Date
June 7, 2022 (Actual)
Study Completion Date
June 7, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CSL312
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
CSL312
Other Intervention Name(s)
Factor XIIa inhibitor monoclonal antibody, garadacimab
Intervention Description
Fully human immunoglobulin G subclass 4/lambda recombinant monoclonal antibody
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Buffer without active ingredient
Primary Outcome Measure Information:
Title
Time-Normalized Number of Hereditary Angioedema (HAE) Attacks Per Month During Treatment Period
Description
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.
Time Frame
First injection up to 6 months
Secondary Outcome Measure Information:
Title
Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period
Description
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 Frame
6 months, first 3-months and second 3-months of treatment period
Title
Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment
Description
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.
Time Frame
6 months, first 3-months and second 3-months of treatment period
Title
Time-Normalized Number of Moderate or Severe HAE Attacks Per Month
Description
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.
Time Frame
6 months, first 3-months and second 3-months of treatment period
Title
Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period
Description
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.
Time Frame
First 3-months and second 3-months of treatment period
Title
Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo
Description
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.
Time Frame
6 months, first 3-months and second 3-months of treatment period
Title
Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART)
Description
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).
Time Frame
Up to 6 months
Title
Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI)
Description
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.
Time Frame
From first dose of study drug up to 3 months after the last injection (approximately 8 months)
Title
Number of Participants With CSL312-induced Anti-CSL312 Antibodies
Time Frame
Up to 8 months
Title
Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs)
Description
Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters.
Time Frame
From first dose of study drug up to 3 months after the last injection (approximately 8 months)
Title
Percentage of Participants With at Least One AE, SAE, and AESI
Description
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.
Time Frame
From first dose of study drug up to 3 months after the last injection (approximately 8 months)
Title
Percentage of Participants With CSL312-induced Anti-CSL312 Antibodies
Time Frame
Up to 6 months
Title
Percentage of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs
Description
Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters.
Time Frame
From first dose of study drug up to 3 months after the last injection (approximately 8 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
CSL Behring LLC
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Research Center of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Medical Research of Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
Raffi Tachdjian MD, Inc.
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Allergy and Asthma Clinical Research
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Institute of Asthma and Allergy
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Bernstein Clinical Research Center LLC
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45231
Country
United States
Facility Name
Pennsylvania State University
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
AARA Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
University of Alberta - Research Transition Facility
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Ottawa Allergy Research Corp
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 1E4
Country
Canada
Facility Name
Gordon Sussman Clinical Research Inc.
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3B 3S6
Country
Canada
Facility Name
Clinique specialisee en allergie de la Capitale
City
Québec
ZIP/Postal Code
G1V 4W2
Country
Canada
Facility Name
Universitätsklinikum Frankfurt Goethe-Universität
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
Facility Name
Charité Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Universitätsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
CRC Clinical Research / Hautklinik und Poliklinik der Universitätsklinik Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
HZRM Hämophilie Zentrum Rhein Main GmbH
City
Mörfelden-Walldorf
ZIP/Postal Code
64546
Country
Germany
Facility Name
Semmelweis University
City
Budapest
ZIP/Postal Code
1088
Country
Hungary
Facility Name
Barzilai University Medical Center
City
Ashkelon
ZIP/Postal Code
7830604
Country
Israel
Facility Name
Hiroshima University Hospital
City
Hiroshima-shi
State/Province
Hiroshima
ZIP/Postal Code
734-8551
Country
Japan
Facility Name
Kobe University Hospital
City
Kobe-shi
State/Province
Hyogo
ZIP/Postal Code
'650-0017
Country
Japan
Facility Name
St.Marianna University School of Medicine Hospital
City
Kawasaki-shi
State/Province
Kanagawa
ZIP/Postal Code
216-8511
Country
Japan
Facility Name
Saitama Medical Center
City
Saitama
State/Province
Kawagoe-shi
ZIP/Postal Code
350-8550
Country
Japan
Facility Name
Saga University Hospital
City
Saga
State/Province
Saga-shi
ZIP/Postal Code
'849-8501
Country
Japan
Facility Name
Koga Community Hospital
City
Yaizu-shi
State/Province
Shizuoka
ZIP/Postal Code
425-0088
Country
Japan
Facility Name
Juntendo University Hospital
City
Bunkyo
State/Province
Tokyo
ZIP/Postal Code
113-8431
Country
Japan
Facility Name
Saiyu Soka Hospital
City
Saitama
ZIP/Postal Code
340-0041
Country
Japan
Facility Name
Amsterdam UMC, Location AMC
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.
If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.
IPD Sharing Time Frame
IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.
IPD Sharing Access Criteria
Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.
An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.
The requesting party must execute an appropriate data sharing agreement before IPD will be made available.
Citations:
PubMed Identifier
36326435
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.
Results Reference
derived
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CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks
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