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

CSL Behring171 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

171

Conditions

Hereditary Angioedema

Interventions

CSL312BIOLOGICAL

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

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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

Locations (44)

Outcomes

Primary Outcomes

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

Time frame: Approximately up to 54 months

Percentage of Participants With TEAE

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

Time frame: Approximately up to 54 months

Number of TEAE

Time frame: 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.

Time frame: 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.

Time frame: Approximately up to 54 months

Secondary Outcomes

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.

Time frame: 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.

Data from ClinicalTrials.gov

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Clinical Research Center of Alabama

Birmingham, Alabama, United States

Research Solutions of Arizona

Litchfield Park, Arizona, United States

Medical Research of Arizona

Scottsdale, Arizona, United States

Little Rock Allergy & Asthma Clinic

Little Rock, Arkansas, United States

Donald S. Levy M.D.

Orange, California, United States

Raffi Tachdjian MD, Inc.

Santa Monica, California, United States

Allergy & Asthma Clinical Research

Walnut Creek, California, United States

Institute for Asthma and Allergy PC

Chevy Chase, Maryland, United States

Bernstein Clinical Research Center, LLC

Cincinnati, Ohio, United States

PennState Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

...and 34 more locations

Time frame: 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).

Time frame: 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\*\[1 - (time-normalized number of HAE attacks per month under CSL312 treatment / time-normalized number of HAE attacks per month during Run-in Period)\].

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: At Months 12, 24, and 36

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

Time frame: 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.

Time frame: 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.

Time frame: Approximately up to 54 months

Percentage of Participants Experiencing TEAE by Severity

Time frame: 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.

Time frame: 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.

Time frame: Approximately up to 54 months

Number of Participants With Laboratory Findings Reported as TEAE

Time frame: 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.

Time frame: Approximately up to 54 months

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

Time frame: Approximately up to 54 months

Percentage of Participants With nC1-INH Experiencing TEAE

Time frame: Approximately up to 54 months

Number of Participants With Anti-CSL312 Antibodies

Time frame: 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.

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