A Study to Investigate CSL312 in Subjects With Hereditary Angioedema (HAE)

Phase 2

Completed

• Conditions: Hereditary Angioedema
• Interventions: Drug: Placebo; Biological: Factor XIIa antagonist monoclonal antibody

• Registration Number: NCT03712228
• Lead Sponsor: CSL Behring

Brief Summary

This is a multicenter, randomized, placebo-controlled, parallel-arm, phase 2 study to investigate the clinical efficacy, pharmacokinetics, and safety of CSL312 as prophylaxis to prevent attacks in subjects with HAE.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-10-17
• Study First Submitted QC: 2018-10-17
• Study First Posted: 2018-10-19
• Study Start: 2018-10-29
• Primary Completion: 2021-10-15
• Study Completion: 2021-10-15
• Status Verified: 2022-10
• Results First Submitted: 2022-10-13
• Results First Submitted QC: 2022-10-13
• Last Update Submitted: 2022-10-13
• Results First Posted: 2022-11-08
• Last Update Posted: 2022-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

• Male or female
• Aged ≥ 18 to ≤ 65 years
• A diagnosis of C1-INH HAE or FXII/PLG HAE;
• For subjects with C1-INH HAE: ≥ 4 HAE attacks over a consecutive 2-month period during the 3 months before Screening, as documented in the subject's medical record.

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Exclusion Criteria

• History of clinically significant arterial or venous thrombosis, or current clinically significant prothrombotic risk
• History of an uncontrolled, abnormal bleeding event due to a coagulopathy, or a current clinically significant coagulopathy or clinically significant risks for bleeding events
• Known incurable malignancies

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Subjects with C1-INH HAE receiving buffer only
CSL312 (low)	Factor XIIa antagonist monoclonal antibody	Subjects with C1-INH HAE receiving low dose CSL312
CSL312 (med)	Factor XIIa antagonist monoclonal antibody	Subjects with C1-INH HAE receiving medium dose CSL312
CSL312 (high)	Factor XIIa antagonist monoclonal antibody	Subjects with C1-INH HAE receiving high dose CSL312
CSL312 (med/high)	Factor XIIa antagonist monoclonal antibody	Subjects with C1-INH HAE receiving medium/high dose CSL312

Primary Outcome Measures

Name	Time	Method
The Mean Time Normalized Number of HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1	13 weeks	The time-normalized number of HAE attacks per month during Treatment Period 1 for a subject was calculated as the (number of HAE attacks / length of subject's evaluation period in days) \* 30.4375

Secondary Outcome Measures

Name	Time	Method
The Number of Responder Subjects With C1-INH HAE During Treatment Period 1	13 weeks	Response is defined as a ≥ 50% relative reduction in the time-normalized number of HAE attacks (per month) during Treatment Period 1 compared to each subject's time-normalized number of HAE attacks (per month) during the Run-in Period
The Percentage of Responder Subjects With C1-INH HAE During Treatment Period 1	13 weeks	Response is defined as a ≥ 50% relative reduction in the time-normalized number of HAE attacks (per month) during Treatment Period 1 compared to each subject's time-normalized number of HAE attacks (per month) during the Run-in Period.
The Number of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1	13 weeks
The Percentage of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1	13 weeks
Terminal Elimination Half-life (T1/2) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1	13 weeks
Area Under the Concentration-time Curve in 1 Dosing Interval (AUC0-tau) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1	13 weeks
The Percentage of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1	13 weeks
The Number of Subjects With at Least One (1) HAE Attack Treated With On-demand HAE Medication, in Subjects With C1-INH HAE During Treatment Period 1	13 weeks
The Percentage of Subjects With at Least One (1) HAE Attack Treated With On-demand HAE Medication, in Subjects With C1-INH HAE During Treatment Period 1	13 weeks
Time of Maximum Concentration (Tmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1	13 weeks
Volume of Distribution During the Elimination Phase (Vz/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1	13 weeks
The Number of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1	13 weeks
The Mean Time-normalized Number of Mild, Moderate or Severe HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1	13 weeks	The time-normalized number of HAE attacks per month during Treatment Period 1 for a subject was calculated as the (number of HAE attacks / length of subject's evaluation period in days) \* 30.4375
Maximum Concentration (Cmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1	13 weeks
Clearance (CL/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1	13 weeks
The Number of Subjects With C1-INH HAE With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESI), Injection Site Reactions (ISRs), Binding Antibodies to CSL312 During Treatment Period 1	13 weeks	Adverse events of special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.

Trial Locations

Locations (16)

Donald S. Levy; 🇺🇸 Orange, California, United States

Allergy & Asthma Clinical Research; 🇺🇸 Walnut Creek, California, United States

The Mount Sinai Hospital; 🇺🇸 New York, New York, United States

AARA Research Center; 🇺🇸 Dallas, Texas, United States

Pennsylvania State University; 🇺🇸 Hershey, Pennsylvania, United States

Campbelltown Hospital; 🇦🇺 Campbelltown, New South Wales, Australia

Ottawa Allergy Research Corp; 🇨🇦 Ottawa, Ontario, Canada

Charité Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Universitätsklinikum Frankfurt Goethe-Universität; 🇩🇪 Frankfurt, Germany

Hautklinik und Poliklinik der Universitätsklinik Mainz; 🇩🇪 Mainz, Germany

Barzilai University Medical Center; 🇮🇱 Ashkelon, Israel

Immunoe Health Centers; 🇺🇸 Centennial, Colorado, United States

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Allergy and Clinical Immunology McMaster University; 🇨🇦 Hamilton, Ontario, Canada

HZRM Hämophilie Zentrum Rhein Main GmbH; 🇩🇪 Mörfelden-Walldorf, Germany

Institute for Asthma and Allergy; 🇺🇸 Chevy Chase, Maryland, United States