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Completed

NCT Number: NCT04739059

Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema Attacks

This phase 3b study will evaluate long-term safety and efficacy of CSL312 (also known as garadacimab) when administered subcutaneously (SC)

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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

Campbelltown Hospital / Western Sydney University, Campbelltown, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

CSL312

Biological

Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody

Other names: Factor XIIa inhibitor monoclonal antibody, garadacimab

Primary outcomes

  1. Number of Participants With Treatment-emergent Adverse Events (TEAE)

    Time frame: Approximately up to 54 months

  2. Percentage of Participants With TEAE

    Time frame: Approximately up to 54 months

    The percentage of participants was rounded to one place of decimal.

  3. Number of TEAE

    Time frame: Approximately up to 54 months

  4. TEAE Rates Per Injection

    Time frame: Approximately up to 54 months

    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.

  5. TEAE Rates Per Participant Year

    Time frame: Approximately up to 54 months

    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.

Secondary outcomes

  1. The Time-normalized Number (Per Month) of Hereditary Angioedema (HAE) Attacks During the Run-in Period and Treatment Period

    Time frame: Run-in Period: Up to Day 60 and Treatment Period: Approximately up to 52 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.

  2. The Time-normalized Number (Per Year) of HAE Attacks During Treatment Period

    Time frame: Approximately up to 52 months

    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.

  3. Percentage Reduction in the Attack Rate During the Treatment Period Compared to the Run-in Period

    Time frame: Run-in Period: Up to 60 days and Treatment Period: Approximately up to 52 months

    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).

  4. Number of Participants With Percentage Reduction (of >=50%, >=70%, >=90%, and 100%) in HAE Attacks

    Time frame: Run-in Period: Up to Day 60 and Treatment Period: Approximately up to 52 months

    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)].

  5. The Time-normalized Number (Per Month) of HAE Attacks Requiring On-demand Treatment

    Time frame: Approximately up to 52 months

    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.

  6. The Time-normalized Number (Per Year) of HAE Attacks Requiring On-demand Treatment

    Time frame: Approximately up to 52 months

    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.

  7. The Time-normalized Number (Per Month) of Moderate and/or Severe HAE Attacks

    Time frame: Approximately up to 52 months

    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.

  8. The Time-normalized Number (Per Year) of Moderate and/or Severe HAE Attacks

    Time frame: Approximately up to 52 months

    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.

  9. Number of Participants Rating Their Response to Therapy as Good or Excellent

    Time frame: At Months 12, 24, and 36

    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.

  10. Percentage of Participants Rating Their Response to Therapy as Good or Excellent

    Time frame: At Months 12, 24, and 36

    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.

  11. Number of Participants Experiencing Serious Adverse Events (SAE), Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation

    Time frame: Approximately up to 54 months

  12. Percentage of Participants Experiencing SAE, Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation

    Time frame: Approximately up to 54 months

    The percentage of participants was rounded to one decimal place.

  13. Number of Participants Experiencing TEAE by Severity

    Time frame: Approximately up to 54 months

    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.

  14. Percentage of Participants Experiencing TEAE by Severity

    Time frame: Approximately up to 54 months

    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.

  15. Number of Participants Experiencing Adverse Events of Special Interest (AESI)

    Time frame: Approximately up to 54 months

    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.

  16. Percentage of Participants Experiencing AESI

    Time frame: Approximately up to 54 months

    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.

  17. Number of Participants With Laboratory Findings Reported as TEAE

    Time frame: Approximately up to 54 months

  18. Percentage of Participants With Laboratory Findings Reported as TEAE

    Time frame: Approximately up to 54 months

    The percentage of participant was rounded to one place of decimal.

  19. Number of Participants With Normal C1-esterase Inhibitor (nC1-INH) Experiencing TEAE

    Time frame: Approximately up to 54 months

  20. Percentage of Participants With nC1-INH Experiencing TEAE

    Time frame: Approximately up to 54 months

  21. Number of Participants With Anti-CSL312 Antibodies

    Time frame: At Day 1, Months 6, 12, 36 and 43 (end of treatment [EOT])

  22. Percentage of Participants With Anti-CSL312 Antibodies

    Time frame: At Day 1, Months 6, 12, 36 and 43 (EOT)

    The percentage of participants was rounded to one decimal place.

Sponsors and collaborators

Lead sponsor

CSL Behring

Industry

Registry information

Official study title

An Open-label Study to Evaluate the Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema

Important dates

Study start
2021
Primary completion
2025
Study completion
2025
First posted
Feb 4, 2021
Registry last updated
Jun 2, 2026

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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