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CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04656418
Recruitment Status : Completed
First Posted : December 7, 2020
Results First Posted : June 29, 2023
Last Update Posted : June 29, 2023
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hereditary Angioedema Biological: CSL312 Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Actual Study Start Date : January 27, 2021
Actual Primary Completion Date : June 7, 2022
Actual Study Completion Date : June 7, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Biological: CSL312
Fully human immunoglobulin G subclass 4/lambda recombinant monoclonal antibody
Other Names:
  • Factor XIIa inhibitor monoclonal antibody
  • garadacimab
Placebo Comparator: 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.
 Drug: Placebo
Buffer without active ingredient


Outcome Measures
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Primary Outcome Measures :
  1. Time-Normalized Number of Hereditary Angioedema (HAE) Attacks Per Month During Treatment Period [ Time Frame: 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 :
  1. Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period [ Time Frame: 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.


  2. Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment [ Time Frame: 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.

  3. Time-Normalized Number of Moderate or Severe HAE Attacks Per Month [ Time Frame: 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.

  4. Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period [ Time Frame: 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.

  5. Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo [ Time Frame: 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.

  6. Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) [ Time Frame: 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).

  7. Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI) [ Time Frame: 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.

  8. Number of Participants With CSL312-induced Anti-CSL312 Antibodies [ Time Frame: Up to 8 months ]
  9. Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 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.

  10. Percentage of Participants With at Least One AE, SAE, and AESI [ Time Frame: 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.

  11. Percentage of Participants With CSL312-induced Anti-CSL312 Antibodies [ Time Frame: Up to 6 months ]
  12. Percentage of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs [ Time Frame: 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.


Eligibility Criteria
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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04656418


Locations
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Sponsors and Collaborators
CSL Behring
Investigators
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Study Director: Study Director CSL Behring LLC
  Study Documents (Full-Text)

Documents provided by CSL Behring:
Study Protocol  [PDF] December 8, 2020
Statistical Analysis Plan  [PDF] April 21, 2021

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT04656418    
Other Study ID Numbers: CSL312_3001
2020-000570-25 ( EudraCT Number )
First Posted: December 7, 2020    Key Record Dates
Results First Posted: June 29, 2023
Last Update Posted: June 29, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
 Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Hereditary Complement Deficiency Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes