Hereditary AngioedemaPhase 3NCT04739059
Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema Attacks
A Phase 3 study testing CSL312 in people with Hereditary Angioedema, run by CSL Behring at 44 sites in 14 countries.
Trial summary
This phase 3b study will evaluate long-term safety and efficacy of CSL312 (also known as garadacimab) when administered subcutaneously (SC) Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- CSL312
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 171 participants
- Where
- 44 sitesin 14 countries
- Study dates
- 29 Mar 2021to 21 Nov 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Males and females aged ≥ 12 years
- Diagnosed with clinically confirmed C1-INH HAE
- Experienced ≥ 3 HAE attacks during the 3 months before Screening
- Participated in the Run-in Period for at least 1 month (CSL312-naïve subjects only)
- Experienced at least an average of 1 HAE attack per month during the Run-in Period
Who cannot join
- Concomitant diagnosis of another form of angioedema, such as idiopathic or acquired angioedema or recurrent angioedema associated with urticaria
- Use of C1-INH products, androgens, antifibrinolytics or other small molecule medications for routine prophylaxis against HAE attacks at least 2 weeks before the first day of the Run-in Period
- Use of monoclonal antibodies such as lanadelumab (Takhzyro®) 3 months before the first day of the Run-in Period.
- Female subjects use estrogen-containing oral contraceptives or hormone replacement therapy within 4 weeks prior to screening
- Female or male subjects who are fertile and sexually active not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 30 days after receipt of the last dose of CSL312
- Pregnant, breastfeeding, or not willing to cease breastfeeding
Trial locations and contacts
44 sites in 14 countries.
44 sites in 14 countries
United States11 sites
Clinical Research Center of Alabama
Birmingham, Alabama, 35209
Institute for Asthma and Allergy PC
Chevy Chase, Maryland, 20815
Bernstein Clinical Research Center, LLC
Cincinnati, Ohio, 45236
AARA Research Center
Dallas, Texas, 75231
PennState Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Research Solutions of Arizona
Litchfield Park, Arizona, 85340
Little Rock Allergy & Asthma Clinic
Little Rock, Arkansas, 72205
Donald S. Levy M.D.
Orange, California, 92868
Raffi Tachdjian MD, Inc.
Santa Monica, California, 90404
Medical Research of Arizona
Scottsdale, Arizona, 85251
Allergy & Asthma Clinical Research
Walnut Creek, California, 94598
Japan10 sites
St. Marianna University School of Medicine Hospital
Kanagawa, Kawasaki-shi, 216-8511
Clover Hospital
Kanagawa, Kugenumaishigami, Fujisawa-shi, 251-0025
Mie University Hospital
Mie, Edobashi, Tsu-shi, Edobashi, Tsu-shi
Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital
Miyakojima-ku, Osaka-shi, 534-0021
Saga University Hospital
Saga, Nebeshima, Saga-shi, 849-8501
Saitama Medical Center
Saitama, Kamoda Kawagoe-shi, 350-8550
Saiyu Soka Hospital
Saitama, Matsubara Soka-shi, 340-0041
Koga Community Hospital
Shizuoka, Daikakuji Yaizu-shi, 425-0088
Juntendo University Hospital
Tokyo, Hongo Bunkyo-ku, 113-8431
National Hospital Organization Disaster Medical Center
Tokyo, Midoricho, Tachikawa-shi, 190-0014
Canada5 sites
University of Alberta - Research Transition Facility
Edmonton, Alberta, T6G 2B7
McMaster University
Hamilton, Ontario, L8N 3Z5
Montreal Clinical Research Institute
Montreal, Quebec, H2W 1R7
Ottawa Allergy Research Corp
Ottawa, Ontario, K1H 1E4
Gordon Sussman Clinical Research
Toronto, Ontario, M3B 3S6
Germany4 sites
Charité - Universitätsmedizin Berlin
Berlin, 10117
Universitätsklinikum Frankfurt
Frankfurt, 60590
Johannes Gutenberg-Universität KöR, Hautklinik und Poliklinik der Universitätsmedizin, Clinical Research Center
Mainz, 55131
HZRM Haemophilie Zentrum Rhein Main GmbH
Mörfelden-Walldorf, 64546
Australia3 sites
Campbelltown Hospital / Western Sydney University
Campbelltown, New South Wales, 2560
The Alfred Hospital
Melbourne, Victoria, 3004
Fiona Stanley Hospital, Department of Clinical Immunology
Murdoch, Western Australia, 6150
Czechia2 sites
University hospital St. Anna Ustav klinicke imunologie a alergologie, Fakultní nemocnice u sv. Anny v Brně
Brno, 65691
University Hospital Motol
Prague, 150 06
Spain2 sites
Hospital Universitari General de La Vall d'Hebron
Barcelona, 8035
Hospital Gregorio Marañón, Servicio de Alergia
Madrid, 28007
Hungary1 site
Semmelweis Egyetem Altalanos Orvostudományi Kar Belgyógyászati és Hematológiai Klinika
Budapest, 1088
About this study
Official title: An Open-label Study to Evaluate the Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema
This phase 3b study will evaluate long-term safety and efficacy of CSL312 (also known as garadacimab) when administered subcutaneously (SC)
- Conditions
- Hereditary Angioedema
- Being tested
- CSL312
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CSL312Biological
Also called Factor XIIa inhibitor monoclonal antibody, garadacimab
Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| CSL312 | Experimental | Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody administered subcutaneously Receives: Biological: CSL312 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Measured: Approximately up to 54 months
Percentage of Participants With TEAE
The percentage of participants was rounded to one place of decimal.
Measured: Approximately up to 54 months
Number of TEAE
Measured: Approximately up to 54 months
TEAE Rates Per Injection
The TEAE rate per injection was calculated as the number of TEAE/ total number of injections. The number of injections was defined as the total injections received by participants during the respective safety evaluation period.
Measured: Approximately up to 54 months
TEAE Rates Per Participant Year
The TEAE rate per participant year was calculated as the total number of TEAE/ participant years. Participant years was defined as the sum of the time (in years) that participant were exposed to study treatment during the respective safety evaluation period.
Measured: Approximately up to 54 months
Secondary outcomes (22)
The Time-normalized Number (Per Month) of Hereditary Angioedema (HAE) Attacks During the Run-in Period and 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.
Measured: Run-in Period: Up to Day 60 and Treatment Period: Approximately up to 52 months
The Time-normalized Number (Per Year) of HAE Attacks During Treatment Period
Time-normalized number of HAE attacks per year during treatment was calculated per participant as: [number of HAE attacks / length of participant treatment in days]*365.25.
Measured: Approximately up to 52 months
Percentage Reduction in the Attack Rate During the Treatment Period Compared to the Run-in Period
The percentage reduction 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).
Measured: Run-in Period: Up to 60 days and Treatment Period: Approximately up to 52 months
Number of Participants With Percentage Reduction (of >=50%, >=70%, >=90%, and 100%) in HAE Attacks
The number of participants who achieved a percentage reduction in HAE attacks of >=50% (also considered as responders), >=70%, >=90%, and 100% (attack free) during the Treatment Period compared with the Run-in Period. The percentage reduction in the time-normalized number of HAE attacks per month was calculated as 100*[1 - (time-normalized number of HAE attacks per month under CSL312 treatment / time-normalized number of HAE attacks per month during Run-in Period)].
Measured: Run-in Period: Up to Day 60 and Treatment Period: Approximately up to 52 months
The Time-normalized Number (Per Month) of HAE Attacks 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 during treatment period / length of participant treatment in days]*30.4375.
Measured: Approximately up to 52 months
The Time-normalized Number (Per Year) of HAE Attacks Requiring On-demand Treatment
Time-normalized number of HAE attacks requiring on demand treatment per year was calculated per participant as: [number of HAE attacks requiring on demand treatment during treatment period / length of participant treatment in days]*365.25.
Measured: Approximately up to 52 months
The Time-normalized Number (Per Month) of Moderate and/or Severe HAE Attacks
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.
Measured: Approximately up to 52 months
The Time-normalized Number (Per Year) of Moderate and/or Severe HAE Attacks
Time-normalized number of moderate or severe HAE attacks per year during treatment period was calculated per participant as: [number of moderate or severe HAE attacks /length of participant treatment in days]*365.25.
Measured: Approximately up to 52 months
Number of Participants Rating Their Response to Therapy as Good or Excellent
Number of participants rating their response to therapy as good or excellent was evaluated as per Subject's Global Assessment of Response to Therapy (SGART) questionnaire. SGART is a patient-reported outcome that represents the participant's overall response to treatment 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. Cumulative responses as "Good or Excellent" are reported for this outcome measure.
Measured: At Months 12, 24, and 36
Percentage of Participants Rating Their Response to Therapy as Good or Excellent
Percentage of participants rating their response to therapy as good or excellent was evaluated as per SGART questionnaire. SGART is a patient-reported outcome that represents the participant's overall response to treatment 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. Cumulative responses as "Good or Excellent" are reported for this outcome measure. The percentage of participants was rounded to one place of decimal.
Measured: At Months 12, 24, and 36
Number of Participants Experiencing Serious Adverse Events (SAE), Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation
Measured: Approximately up to 54 months
Percentage of Participants Experiencing SAE, Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation
The percentage of participants was rounded to one decimal place.
Measured: Approximately up to 54 months
Number of Participants Experiencing TEAE by Severity
Severity of AE was assessed by the investigator and categorized as mild, moderate and severe. A mild AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. A moderate AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. A severe AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.
Measured: Approximately up to 54 months
Percentage of Participants Experiencing TEAE by Severity
Severity of AE was assessed by the investigator and categorized as mild, moderate and severe. A mild AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. A moderate AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. A severe AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention. The percentage of participants was rounded to one decimal place.
Measured: Approximately up to 54 months
Number of Participants Experiencing Adverse Events of Special Interest (AESI)
The AESI defined for this study were thromboembolic events, abnormal bleeding events, and severe hypersensitivity including anaphylaxis. The AESI reported have been identified by investigators.
Measured: Approximately up to 54 months
Percentage of Participants Experiencing AESI
The AESI defined for this study were thromboembolic events, abnormal bleeding events, and severe hypersensitivity including anaphylaxis. The AESI reported have been identified by investigators.
Measured: Approximately up to 54 months
Number of Participants With Laboratory Findings Reported as TEAE
Measured: Approximately up to 54 months
Percentage of Participants With Laboratory Findings Reported as TEAE
The percentage of participant was rounded to one place of decimal.
Measured: Approximately up to 54 months
Number of Participants With Normal C1-esterase Inhibitor (nC1-INH) Experiencing TEAE
Measured: Approximately up to 54 months
Percentage of Participants With nC1-INH Experiencing TEAE
Measured: Approximately up to 54 months
Number of Participants With Anti-CSL312 Antibodies
Measured: At Day 1, Months 6, 12, 36 and 43 (end of treatment [EOT])
Percentage of Participants With Anti-CSL312 Antibodies
The percentage of participants was rounded to one decimal place.
Measured: At Day 1, Months 6, 12, 36 and 43 (EOT)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2021
- Study start29 Mar 2021
- Primary completion21 Nov 2025
- Study completion21 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- More trials run by CSL BehringThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04739059
- Sponsor's protocol ID
- CSL312_3002
- Other IDs
- 2020-003918-12
- Status last verified
- Apr 2026
- First submitted
- 1 Feb 2021
- Last updated
- 2 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Craig TJ, Guilarte M, Li HH, Anderson J, Martinez Saguer I, Jacobs JS, Tachdjian R, Farkas H, Yang WH, Ohsawa I, Hakl R, Pollen M, Pragst I, Lawo JP, Shetty H, Nenci C, Magerl M. Long-Term Integrated Safety and Efficacy of Garadacimab for Hereditary Angioedema Prophylaxis. Adv Ther. 2026 Jun 10. doi: 10.1007/s12325-026-03628-x. Online ahead of print.
PubMed 42268494Guilarte M, Lumry WR, Magerl M, Martinez Saguer I, Reshef A, Sobotkova M, Braverman J, Lawo JP, Wieman L, Nenci C, Katelaris CH. Garadacimab improves long-term health-related quality of life in patients with hereditary angioedema. Allergy Asthma Proc. 2025 May 1;46(3):192-199. doi: 10.2500/aap.2025.46.250027.
PubMed 40380363Staubach P, Craig TJ, Fukuda T, Aygoren-Pursun E, Hakl R, Braverman J, Lawo JP, Pollen M, Nenci C, Li PH, Farkas H. Becoming attack-free further improves health-related quality of life in patients with hereditary angioedema receiving garadacimab. Allergy Asthma Proc. 2025 May 1;46(3):200-208. doi: 10.2500/aap.2025.46.250026.
PubMed 40380356