CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks
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
2 other identifiers
interventional
64
7 countries
28
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Jan 2021
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 1, 2020
CompletedFirst Posted
Study publicly available on registry
December 7, 2020
CompletedStudy Start
First participant enrolled
January 27, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 7, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 7, 2022
CompletedResults Posted
Study results publicly available
June 29, 2023
CompletedJune 29, 2023
June 1, 2023
1.4 years
December 1, 2020
June 7, 2023
June 7, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (12)
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
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 Moderate or Severe HAE Attacks Per Month
6 months, first 3-months and second 3-months of treatment period
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
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
- +7 more secondary outcomes
Study Arms (2)
CSL312
EXPERIMENTALParticipants 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 COMPARATORParticipants 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- Concomitant diagnosis of another form of angioedema such as idiopathic or acquired angioedema, recurrent angioedema associated with urticarial or hereditary angioedema type 3
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- CSL Behringlead
Study Sites (28)
Clinical Research Center of Alabama
Birmingham, Alabama, 35209, United States
Medical Research of Arizona
Scottsdale, Arizona, 85251, United States
Raffi Tachdjian MD, Inc.
Santa Monica, California, 90404, United States
Allergy and Asthma Clinical Research
Walnut Creek, California, 94598, United States
Institute of Asthma and Allergy
Chevy Chase, Maryland, 20815, United States
Bernstein Clinical Research Center LLC
Cincinnati, Ohio, 45231, United States
Pennsylvania State University
Hershey, Pennsylvania, 17033, United States
AARA Research Center
Dallas, Texas, 75231, United States
University of Alberta - Research Transition Facility
Edmonton, Alberta, T6G 2B7, Canada
Ottawa Allergy Research Corp
Ottawa, Ontario, K1H 1E4, Canada
Gordon Sussman Clinical Research Inc.
Toronto, Ontario, M3B 3S6, Canada
Clinique specialisee en allergie de la Capitale
Québec, G1V 4W2, Canada
Universitätsklinikum Frankfurt Goethe-Universität
Frankfurt am Main, Hesse, 60590, Germany
Charité Universitätsmedizin Berlin
Berlin, 10117, Germany
Universitätsklinikum Leipzig
Leipzig, 04103, Germany
CRC Clinical Research / Hautklinik und Poliklinik der Universitätsklinik Mainz
Mainz, 55131, Germany
HZRM Hämophilie Zentrum Rhein Main GmbH
Mörfelden-Walldorf, 64546, Germany
Semmelweis University
Budapest, 1088, Hungary
Barzilai University Medical Center
Ashkelon, 7830604, Israel
Hiroshima University Hospital
Hiroshima, Hiroshima, 734-8551, Japan
Kobe University Hospital
Kobe, Hyōgo, '650-0017, Japan
St.Marianna University School of Medicine Hospital
Kawasaki-shi, Kanagawa, 216-8511, Japan
Saitama Medical Center
Saitama, Kawagoe-shi, 350-8550, Japan
Saga University Hospital
Saga, Saga-shi, '849-8501, Japan
Koga Community Hospital
Yaizu-shi, Shizuoka, 425-0088, Japan
Juntendo University Hospital
Bunkyo, Tokyo, 113-8431, Japan
Saiyu Soka Hospital
Saitama, 340-0041, Japan
Amsterdam UMC, Location AMC
Amsterdam, 1105 AZ, Netherlands
Related Publications (2)
Craig TJ, Reshef A, Li HH, Jacobs JS, Bernstein JA, Farkas H, Yang WH, Stroes ESG, Ohsawa I, Tachdjian R, Manning ME, Lumry WR, Saguer IM, Aygoren-Pursun E, Ritchie B, Sussman GL, Anderson J, Kawahata K, Suzuki Y, Staubach P, Treudler R, Feuersenger H, Glassman F, Jacobs I, Magerl M. Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Apr 1;401(10382):1079-1090. doi: 10.1016/S0140-6736(23)00350-1. Epub 2023 Feb 28.
PMID: 36868261DERIVEDBeard 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.
PMID: 36326435DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- CSL Behring
Study Officials
- STUDY DIRECTOR
Study Director
CSL Behring LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 1, 2020
First Posted
December 7, 2020
Study Start
January 27, 2021
Primary Completion
June 7, 2022
Study Completion
June 7, 2022
Last Updated
June 29, 2023
Results First Posted
June 29, 2023
Record last verified: 2023-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- 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.
- 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.
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.