CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks

• ClinicalTrials.gov Identifier: NCT04656418
• Recruitment Status: Completed
• First Posted: December 7, 2020
• Last Update Posted: January 13, 2023
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

Tracking Information

• First Submitted Date: December 1, 2020
• First Posted Date: December 7, 2020
• Last Update Posted Date: January 13, 2023
• Actual Study Start Date: January 13, 2021
• Actual Primary Completion Date: June 7, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 1, 2020): Time-normalized number of hereditary angioedema (HAE) attacks during treatment period [ Time Frame: up to 6 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 5, 2020)

• Change in the HAE attack rate during the treatment period compared to the run-in period [ Time Frame: up to 6 months ]
• Time-normalized number of attacks requiring on-demand treatment [ Time Frame: 6 months, and first 3 months and second 3 months ]
• Time-normalized number of moderate and/or severe HAE attacks [ Time Frame: 6 months, and first 3 months and second 3 months ]
• Time-normalized number of HAE attacks at various timepoints during the treatment period [ Time Frame: First 3 months and second 3 months and 6 months ]
• Percent change in the time-normalized number of HAE attacks between CSL312 and Placebo [ Time Frame: 6 months, and first 3 months and second 3 months ]
• Subject's Global Assessment of Response to Therapy (SGART) [ Time Frame: Up to 6 months ]
  Comparison of the distribution of responses to therapy between CSL312 and placebo based on proportions of subjects with"excellent," "good," "fair," "poor or none" response to therapy
• Number of subjects with adverse events, adverse events of special interest, serious adverse events, CSL312-induced anti-CSL312 antibodies, clinically significant abnormalities in laboratory assessments [ Time Frame: Up to 8 months ]
• Percent of subjects with Adverse events, adverse events of special interest, serious adverse events, CSL312-induced anti-CSL312 antibodies, clinically significant abnormalities in laboratory assessments [ Time Frame: Up to 8 months ]

Original Secondary Outcome Measures (submitted: December 1, 2020)

• Reduction in the HAE attack rate during the treatment period compared to the run-in period [ Time Frame: up to 6 months ]
• Time-normalized number of attacks requiring on-demand treatment [ Time Frame: 6 months, and first 3 months and second 3 months ]
• Time-normalized number of moderate and/or severe HAE attacks [ Time Frame: 6 months, and first 3 months and second 3 months ]
• Time-normalized number of HAE attacks at various timepoints during the treatment period [ Time Frame: First 3 months and second 3 months and 6 months ]
• Percent reduction in the time-normalized number of HAE attacks between CSL312 and Placebo [ Time Frame: 6 months, and first 3 months and second 3 months ]
• Subject's Global Assessment of Response to Therapy (SGART) [ Time Frame: Up to 6 months ]
  Comparison of the distribution of responses to therapy between CSL312 and placebo based on proportions of subjects with"excellent," "good," "fair," "poor or none" response to therapy
• Number of subjects with adverse events, adverse events of special interest, serious adverse events, CSL312-induced anti-CSL312 antibodies, clinically significant abnormalities in laboratory assessments [ Time Frame: Up to 8 months ]
• Percent of subjects with Adverse events, adverse events of special interest, serious adverse events, CSL312-induced anti-CSL312 antibodies, clinically significant abnormalities in laboratory assessments [ Time Frame: Up to 8 months ]

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

Descriptive Information

• Brief Title: CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks
• Official Title: A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-arm Study to Investigate the Efficacy and Safety of Subcutaneous Administration of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema
• Brief Summary: This is a multicenter, double-blind, randomized, placebo-controlled, parallel-arm study to investigate the efficacy and safety of subcutaneous administration of CSL312 (garadacimab) in the prophylactic treatment of hereditary angioedema
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Hereditary Angioedema

Intervention

• Biological: CSL312
  Fully human immunoglobulin G subclass 4/lambda recombinant monoclonal antibody
  Other Names:

  • Factor XIIa antagonist monoclonal antibody
  • garadacimab
• Drug: Placebo
  Buffer without active ingredient

Study Arms

• Experimental: CSL312
  Subjects with C1-INH HAE receiving CSL312
  Intervention: Biological: CSL312
• Placebo Comparator: Placebo
  Subjects with C1-INH HAE receiving buffer only
  Intervention: Drug: Placebo

• Publications *: Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 22, 2022): 64
• Original Estimated Enrollment (submitted: December 1, 2020): 60
• Actual Study Completion Date: June 7, 2022
• Actual Primary Completion Date: June 7, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female ≥ 12 years of age; diagnosed with clinically confirmed C1-INH hereditary angioedema; experience ≥ 3 attacks during the 3 months before screening

Exclusion Criteria:

• Concomitant diagnosis of another form of angioedema such as idiopathic or acquired angioedema, recurrent angioedema associated with urticarial or hereditary angioedema type 3

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: Canada, Germany, Hungary, Israel, Japan, Netherlands, United States

Administrative Information

• NCT Number: NCT04656418
• Other Study ID Numbers: CSL312_3001; 2020-000570-25 ( 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 LLC

• PRS Account: CSL Behring
• Verification Date: January 2023