CSL312_3003 Safety and Pharmacokinetic Study in Subjects 2 to 11 Years of Age With Hereditary Angioedema

A Phase 3 Open-label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema in Pediatric Subjects 2 to 11 Years of Age

The purpose of this study is to investigate the safety, PK / PD, and efficacy of SC CSL312 for prophylactic treatment of pediatric subjects with HAE.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema (HAE)
• Intervention / Treatment: Biological: CSL312

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Campbelltown, Australia, NSW 2560
    • Campbelltown Hospital, Western Sydney University
• Canada
  • Ottawa, Canada, K1H1E4
    • Ottawa Allergy Research Corp
• Germany
  • Berlin, Germany, 12203
    • Charité - Universitätsmedizin Berlin
  • Frankfurt am Main, Germany, 60590
    • Universitätsklinikum Frankfurt
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60596
      • HZRM Hämophilie Zentrum Rhein Main GmbH
• Israel
  • Ashkelon, Israel, 7830604
    • Barzilai University Medical Center
• United States
  • Arizona
    • Litchfield Park, Arizona, United States, 85340
      • Research Solutions of Arizona
    • Scottsdale, Arizona, United States, 85251
      • Medical Research of Arizona
  • California
    • Orange, California, United States, 92868
      • Donald S. Levy M.D.
    • Santa Monica, California, United States, 90404
      • Raffi Tachdjian MD, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Bernstein Clinical Research
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • PennState Health Milton S. Hershey Medical Center
  • Texas
    • Dallas, Texas, United States, 75231
      • AARA Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female
2. Aged 2 to 11 years, inclusive, with body weight ≥ 10th percentile based on age
3. Diagnosed with clinically confirmed C1-INH HAE
4. Experienced ≥ 2 HAE attacks during the 6 months before Screening

Exclusion Criteria:

1. Concomitant diagnosis of another form of angioedema, such as idiopathic or acquired angioedema, recurrent angioedema associated with urticaria, or HAE type 3
2. Use of C1-INH products, androgens, antifibrinolytics, approved or future approved medications, or other small molecule medications for routine prophylaxis against HAE attacks within a minimum of 2 weeks before the Treatment Period
3. Participation in another interventional clinical study during the 30 days before the Treatment Period or within 5 half-lives of the final dose of the investigational product administered during the previous interventional study, whichever is longer
4. Having laboratory clinical abnormalities assessed as clinically significant by the investigator in results of hematology or chemistry assessments performed during Screening
5. Currently receiving a therapy not permitted during the study
6. Being pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSL312; Ages 2-5 years and 6-11 years will have specific subcutaneous dosing schedules	Biological: CSL312; Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody administered subcutaneously (SC); Other Names: Garadacimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAE)		Up to Month 12
Percentage of Participants With TEAE	The percentage of participants was rounded to one place of decimal.	Up to Month 12
Number of TEAE		Up to Month 12
TEAE Rates Per Injection	The TEAE rate per injection was calculated as the number of TEAE/ number of injections. The number of injections was defined as the total injections a participant received during the Safety Evaluation Period under the dosing regimen to which the TEAE was assigned.	Up to Month 12
TEAE Rates Per Participant-Year	The TEAE rate per participant year was calculated as number of TEAEs/ participant years. Participant-years of exposure were calculated as the sum of each participant's exposure duration (in years) under the specified dosing regimen or overall. For the time assigned to a dosing regimen, each study day was counted under the corresponding regimen.	Up to Month 12
Maximum Concentration (Cmax) of CSL312 at Steady-state		Up to Month 12
Trough Concentration (Ctrough) of CSL312 at Steady-state		At Months 3, 4, 6, 9, 10, and 12
Time to Maximum Concentration (Tmax) of CSL312 at Steady-State		Up to Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-normalized Number of HAE Attacks Per Month	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.	Up to Month 12
Time-normalized Number of HAE Attacks Per Year	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.	Up to Month 12
Time-normalized Number of HAE Attacks Treated With On-demand Treatment Per Month	The time-normalized number of HAE attacks per month treated with on-demand treatment were calculated as follows: [(Number of HAE attacks treated with on - demand treatment during treatment period)/ Length of participant treatment in days] ∗ 30.4375.	Up to Month 12
Time-normalized Number of HAE Attacks Treated With On-demand Treatment Per Year	The time-normalized number of HAE attacks per year treated with on-demand treatment were calculated as follows: [(Number of HAE attacks treated with on - demand treatment during treatment period)/ Length of participant treatment in days] ∗ 365.25.	Up to Month 12
Time-normalized Number of Moderate and/or Severe HAE Attacks Per Month	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.	Up to Month 12
Time-normalized Number of Moderate and/or Severe HAE Attacks Per Year	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] * 365.25.	Up to Month 12
Percentage Reduction in the Time-normalized Number of HAE Attacks	The percentage reduction in the time-normalized number of HAE attacks was calculated within a participant as follows: 100*[ 1 - (Time-normalized number of HAE attacks per month during treatment period/Time-normalized number of HAE attacks per month from historical data)].	Up to Month 12
Number of Participants Experiencing at Least Greater Than or Equal to (>=) 50 Percent (%), >= 70%, >= 90%, or Equal to 100% (Attack-free) Reduction in the Time-normalized Number of HAE Attacks	A participant was classified as a responder if the percentage reduction in the time-normalized number of HAE attacks under treatment compared to the time-normalized number of HAE attacks documented in the medical records was >= 50%. Percent Reduction = 100 * [1 - (time-normalized number of HAE attacks during corresponding time window / time-normalized number of HAE attacks based on historical data)]. Here number of participants experiencing at least >= 50%, >= 70%, >= 90%, or equal to 100% (Attack-free) reduction in the time-normalized number of HAE attacks are reported. The number of responders at each reduction category have been reported.	Up to Month 12
Number of Participants Experiencing Serious Adverse Events (SAE), Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation		Up to Month 12
Percentage of Participants Experiencing SAE, Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation	The percentage of participants was rounded to one decimal place.	Up to Month 12
Number of Participants With TEAE by Severity	Severity of AE was assessed by the investigator and categorized as mild, moderate and severe where: 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. 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. Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.	Up to Month 12
Percentage of Participants With TEAE by Severity	Severity of AE was assessed by the investigator and categorized as mild, moderate and severe where: 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. 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. 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 place of decimal.	Up to Month 12
Number of Participants With Anti-CSL312 Antibodies		At Day 1, Months 6 and 12
Percentage of Participants With Anti-CSL312 Antibodies	The percentage of participants was rounded to one place of decimal.	At Day 1, Months 6 and 12
Number of Participants With Adverse Events of Special Interest (AESI)	AESI included severe hypersensitivity including anaphylaxis. The AESI reported have been identified by investigators and suggestive events were independently identified for further review with a Standardized MedDRA Query (SMQ).	Up to Month 12
Percentage of Participants With AESI	AESI included severe hypersensitivity including anaphylaxis. The AESI reported have been identified by investigators and suggestive events were independently identified for further review with an SMQ. The percentage of participants was rounded to one place of decimal.	Up to Month 12
FXIIa-mediated Kallikrein Activity		At Months 3, 4, and 12 and pre-dose and post dose at Months 6, 9, and 10
Percent of Baseline FXIIa-mediated Kallikrein Activity	Percent of Baseline at Visit [i] = 100 * (actual value at Visit [i] / Baseline value), where Baseline is defined as the most recent, non-missing value before the first IP administration (including unscheduled visits). Here unit of measure is Percent (%) of FXIIa-mediated Kallikrein Activity.	At Months 3, 4, and 12 and pre-dose and post dose at Months 6, 9, and 10
Number of Participants With Laboratory Findings Reported as AE		Up to Month 12
Percentage of Participants With Laboratory Findings Reported as AE	The participant data were rounded to one decimal place.	Up to Month 12

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2023
• Primary Completion (Actual): November 19, 2025
• Study Completion (Actual): November 19, 2025

Study Registration Dates

• First Submitted: April 4, 2023
• First Submitted That Met QC Criteria: April 17, 2023
• First Posted (Actual): April 19, 2023

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immunologic Deficiency Syndromes; Skin Diseases; Urticaria; Skin Diseases, Vascular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Angioedema; Angioedemas, Hereditary
• Other Study ID Numbers: CSL312_3003; 2022-502386-13-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

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.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No