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

• ClinicalTrials.gov Identifier: NCT05819775
• Recruitment Status: Recruiting
• First Posted: April 19, 2023
• Last Update Posted: April 10, 2024
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

Tracking Information

• First Submitted Date: April 4, 2023
• First Posted Date: April 19, 2023
• Last Update Posted Date: April 10, 2024
• Actual Study Start Date: May 30, 2023
• Estimated Primary Completion Date: November 11, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 17, 2023)

• Number of subjects with treatment emergent adverse events (TEAEs) [ Time Frame: At least 14 months ]
• Percent of subjects with TEAEs [ Time Frame: At lease 14 months ]
• Number of TEAEs [ Time Frame: At least 14 months ]
• TEAE rates per injection [ Time Frame: At least 14 months ]
• TEAE rates per subject year [ Time Frame: At least 14 months ]
• Maximum concentration (Cmax) of CSL312 at steady-state [ Time Frame: At least 12 months ]
• Trough concentration (Ctrough) of CSL312 at steady-state [ Time Frame: At least 12 months ]
• Time to maximum concentration (Tmax) of CSL312 at steady-state [ Time Frame: At least 12 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 8, 2024)

• Time-normalized number of HAE attacks per month and per year [ Time Frame: At least 12 months ]
• Time-normalized number of HAE attacks treated with on-demand treatment per month and per year [ Time Frame: At least 12 months ]
• Time-normalized number of moderate and / or severe HAE attacks per month and per year [ Time Frame: At least 12 months ]
• Percentage reduction in the time-normalized number of HAE attacks [ Time Frame: At least 12 months ]
• The number of subjects experiencing at least ≥ 50%, ≥ 70%, ≥ 90%, or equal to 100% (attack-free) reduction in the time-normalized number of HAE attacks [ Time Frame: At least 12 months ]
• Number of subjects with serious adverse events (SAEs) [ Time Frame: At least 14 months ]
• Percent of subjects with SAEs [ Time Frame: At least 14 months ]
• Number of subjects experiencing death [ Time Frame: At least 14 months ]
• Percent of subjects experiencing death [ Time Frame: At least 14 months ]
• Number of subjects with related TEAEs [ Time Frame: At least 14 months ]
• Percent of subjects with related TEAEs [ Time Frame: At least 14 months ]
• Number of subjects with TEAEs leading to study discontinuation [ Time Frame: At least 14 months ]
• Percent of subjects with TEAEs leading to study discontinuation [ Time Frame: At least 14 months ]
• Number of subjects with TEAEs by severity [ Time Frame: At least 14 months ]
• Percent of subjects with TEAEs by severity [ Time Frame: At least 14 months ]
• Number of subjects with Anti-CSL312 antibodies [ Time Frame: At least 14 months ]
• Percent of subjects with Anti-CSL312 antibodies [ Time Frame: At least 14 months ]
• Number of subjects with adverse events of special interest (AESIs) [ Time Frame: At least 14 months ]
• Percent of subjects with AESIs [ Time Frame: At least 14 months ]
• FXIIa-mediated kallikrein activity [ Time Frame: At least 12 months ]
  Blood samples will be collected on the same day as CSL312 administration for assessment of FXIIa-mediated kallikrein activity
• Number of subjects with laboratory findings reported as AEs [ Time Frame: At least 14 months ]
• Percent of subjects with laboratory findings reported as AEs [ Time Frame: At least 14 months ]

Original Secondary Outcome Measures (submitted: April 17, 2023)

• Time-normalized number of HAE attacks per month and per year [ Time Frame: At least 12 months ]
• Time-normalized number of HAE attacks treated with on-demand treatment per month and per year [ Time Frame: At least 12 months ]
• Time-normalized number of moderate and / or severe HAE attacks per month and per year [ Time Frame: At least 12 months ]
• Percentage reduction in the time-normalized number of HAE attacks [ Time Frame: At least 12 months ]
• The number of subjects experiencing at least ≥ 50%, ≥ 70%, ≥ 90%, or equal to 100% (attack-free) reduction in the time-normalized number of HAE attacks [ Time Frame: At least 12 months ]
• Number of subjects with serious adverse events (SAEs) [ Time Frame: At least 14 months ]
• Percent of subjects with SAEs [ Time Frame: At least 14 months ]
• Number of subjects experiencing death [ Time Frame: At least 14 months ]
• Percent of subjects experiencing death [ Time Frame: At least 14 months ]
• Number of subjects with related TEAEs [ Time Frame: At least 14 months ]
• Percent of subjects with related TEAEs [ Time Frame: At least 14 months ]
• Number of subjects with TEAEs leading to study discontinuation [ Time Frame: At least 14 months ]
• Percent of subjects with TEAEs leading to study discontinuation [ Time Frame: At least 14 months ]
• Number of subjects with TEAEs by severity [ Time Frame: At least 14 months ]
• Percent of subjects with TEAEs by severity [ Time Frame: At least 14 months ]
• Number of subjects with Anti-CSL312 antibodies [ Time Frame: At least 14 months ]
• Percent of subjects with Anti-CSL312 antibodies [ Time Frame: At least 14 months ]
• Number of subjects with adverse events of special interest (AESIs) [ Time Frame: At least 14 months ]
• Percent of subjects with AESIs [ Time Frame: At least 14 months ]
• FXIIa-mediated kallikrein activity [ Time Frame: At least 12 months ]
  Blood samples will be collected on the same day as CSL312 administration for assessment of FXIIa-mediated kallikrein activity

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CSL312_3003 Safety and Pharmacokinetic Study in Subjects 2 to 11 Years of Age With Hereditary Angioedema
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hereditary Angioedema (HAE)

Intervention

Biological: CSL312

Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody administered subcutaneously (SC)

Other Name: Garadacimab

Study Arms

Experimental: CSL312

Ages 2-5 years and 6-11 years will have specific subcutaneous dosing schedules

Intervention: Biological: CSL312

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 8, 2024): 20
• Original Estimated Enrollment (submitted: April 17, 2023): 12
• Estimated Study Completion Date: November 11, 2026
• Estimated Primary Completion Date: November 11, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 11 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Trial Registration Coordinator; 1-610-878-4000; clinicaltrials@cslbehring.com

• Listed Location Countries: Israel, United States

Administrative Information

• NCT Number: NCT05819775
• Other Study ID Numbers: CSL312_3003; 2022-502386-13-00 ( EU Trial (CTIS) Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• 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.

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.

• Current Responsible Party: CSL Behring
• Original Responsible Party: Same as current
• Current Study Sponsor: CSL Behring
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; CSL Behring

• PRS Account: CSL Behring
• Verification Date: April 2024