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Completed

NCT Number: NCT04656418

CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks

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.

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Key information

Conditions

Hereditary Angioedema Angioedema Angioedemas, Hereditary Cardiovascular Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hereditary Complement Deficiency Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Immunologic Deficiency Syndromes Primary Immunodeficiency Diseases Skin Diseases Skin Diseases, Vascular Skin and Connective Tissue Diseases Urticaria Vascular Diseases

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of Alberta - Research Transition Facility, Edmonton, Alberta, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

CSL312

Biological

Fully human immunoglobulin G subclass 4/lambda recombinant monoclonal antibody

Other names: Factor XIIa inhibitor monoclonal antibody, garadacimab

Placebo

Drug

Buffer without active ingredient

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

CSL Behring

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Dec 7, 2020
Registry last updated
Jun 29, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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