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

• ClinicalTrials.gov Identifier: NCT04739059
• Recruitment Status: Active, not recruiting
• First Posted: February 4, 2021
• Last Update Posted: May 8, 2024
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

Tracking Information

• First Submitted Date: February 1, 2021
• First Posted Date: February 4, 2021
• Last Update Posted Date: May 8, 2024
• Actual Study Start Date: March 29, 2021
• Estimated Primary Completion Date: November 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 2, 2022)

• Number of subjects with treatment emergent adverse events (TEAEs) [ Time Frame: Up to 45 months ]
• Percentage of subjects with TEAEs [ Time Frame: Up to 45 months ]
• TEAEs rates per injection [ Time Frame: Up to 45 months ]
• TEAEs rates per subject year [ Time Frame: Up to 45 months ]

Original Primary Outcome Measures (submitted: February 1, 2021)

• Number of subjects with treatment emergent adverse events (TEAEs) [ Time Frame: Up to 32 months ]
• Percentage of subjects with TEAEs [ Time Frame: Up to 32 months ]
• TEAEs rates per injection [ Time Frame: Up to 32 months ]
• TEAEs rates per subject year [ Time Frame: Up to 32 months ]

Current Secondary Outcome Measures (submitted: November 2, 2022)

• The time-normalized number (per month and year) of Hereditary Angioedema (HAE attacks) for the entire study [ Time Frame: Up to 43 months ]
• The percentage reduction and 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 on Treatment compared to Run-in Period [ Time Frame: Up to 43 months ]
• The time-normalized number (per month and year) of HAE attacks requiring on-demand treatment in subjects on treatment [ Time Frame: Up to 43 months ]
• The time-normalized number (per month and year) of moderate and/or severe HAE attacks in subjects on treatment [ Time Frame: Up to 43 months ]
• Number and percentage of subjects rating their response to therapy as good or excellent [ Time Frame: Up to 43 months ]
• The number and percentage of subjects experiencing TEAEs [ Time Frame: Up to 45 months ]
• The number and percentage of subjects experiencing adverse events of special interest (AESIs) [ Time Frame: Up to 45 months ]
• The number and percentage of subjects experiencing serious adverse events (SAEs), including deaths [ Time Frame: Up to 45 months ]
• The number and percentage of subjects experiencing CSL312 induced anti-CSL312 antibodies [ Time Frame: Up to 45 months ]

Original Secondary Outcome Measures (submitted: February 1, 2021)

• The time-normalized number (per month and year) of Hereditary Angioedema (HAE attacks) for the entire study [ Time Frame: Up to 34 months ]
• The percentage reduction and 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 on Treatment compared to Run-in Period [ Time Frame: Up to 34 months ]
• The time-normalized number (per month and year) of HAE attacks requiring on-demand treatment in subjects on treatment [ Time Frame: Up to 32 months ]
• The time-normalized number (per month and year) of moderate and/or severe HAE attacks in subjects on treatment [ Time Frame: Up to 32 months ]
• Number and percentage of subjects rating their response to therapy as good or excellent [ Time Frame: Up to 32 months ]
• The number and percentage of subjects experiencingTEAEs with CSL312 or while on placebo [ Time Frame: Up to 32 months ]
• The number and percentage of subjects experiencing adverse events of special interest (AESIs) with CSL312 or while on placebo [ Time Frame: Up to 32 months ]
• The number and percentage of subjects experiencing TEAEs for naïve C1-INH subjects only with CSL312 or while on placebo [ Time Frame: Up to 32 months ]
• The number and percentage of subjects experiencing serious adverse events (SAEs), including deaths, with CSL312 or while on placebo [ Time Frame: Up to 32 months ]
• The number and percentage of subjects experiencing CSL312 induced anti-CSL312 antibodies with CSL312 or while on placebo [ Time Frame: Up to 32 months ]

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

Descriptive Information

• Brief Title: Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema Attacks
• Official Title: An Open-label Study to Evaluate the Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema
• Brief Summary: This phase 3b study will evaluate long-term safety and efficacy of CSL312 (also known as garadacimab) when administered subcutaneously (SC)
• 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: Prevention
• Condition: Hereditary Angioedema

Intervention

Biological: CSL312

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

Other Names:

• Factor XIIa inhibitor monoclonal antibody
• garadacimab

Study Arms

Experimental: CSL312

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

Intervention: Biological: CSL312

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 28, 2022): 171
• Original Estimated Enrollment (submitted: February 1, 2021): 150
• Estimated Study Completion Date: November 2025
• Estimated Primary Completion Date: November 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Czechia, Germany, Hong Kong, Hungary, Israel, Japan, Netherlands, New Zealand, Russian Federation, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT04739059
• Other Study ID Numbers: CSL312_3002; 2020-003918-12 ( EudraCT 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 requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

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.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.

Access Criteria

Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made 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: May 2024