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

Primary Purpose

Hereditary Angioedema

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Factor XIIa antagonist monoclonal antibody
Placebo
Sponsored by
CSL Behring
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hereditary Angioedema

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

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

Sites / Locations

  • Donald S. Levy
  • Allergy & Asthma Clinical Research
  • Immunoe Health Centers
  • Institute for Asthma and Allergy
  • The Mount Sinai Hospital
  • Pennsylvania State University
  • AARA Research Center
  • Campbelltown Hospital
  • University of Alberta
  • Allergy and Clinical Immunology McMaster University
  • Ottawa Allergy Research Corp
  • Charité Universitätsmedizin Berlin
  • Universitätsklinikum Frankfurt Goethe-Universität
  • Hautklinik und Poliklinik der Universitätsklinik Mainz
  • HZRM Hämophilie Zentrum Rhein Main GmbH
  • Barzilai University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Placebo

CSL312 (low)

CSL312 (med)

CSL312 (high)

CSL312 (med/high)

Arm Description

Subjects with C1-INH HAE receiving buffer only

Subjects with C1-INH HAE receiving low dose CSL312

Subjects with C1-INH HAE receiving medium dose CSL312

Subjects with C1-INH HAE receiving high dose CSL312

Subjects with C1-INH HAE receiving medium/high dose CSL312

Outcomes

Primary Outcome Measures

The Mean Time Normalized Number of HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
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

The Number of Responder Subjects With C1-INH HAE During Treatment Period 1
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
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
The Percentage of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1
The Number of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
The Percentage of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
The Mean Time-normalized Number of Mild, Moderate or Severe HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
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
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
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
Maximum Concentration (Cmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Area Under the Concentration-time Curve in 1 Dosing Interval (AUC0-tau) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Time of Maximum Concentration (Tmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Terminal Elimination Half-life (T1/2) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Clearance (CL/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Volume of Distribution During the Elimination Phase (Vz/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
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
Adverse events of special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.

Full Information

First Posted
October 17, 2018
Last Updated
October 13, 2022
Sponsor
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT03712228
Brief Title
A Study to Investigate CSL312 in Subjects With Hereditary Angioedema (HAE)
Official Title
A Multicenter, Randomized, Placebo-controlled, Parallel-arm Study to Investigate the Efficacy, Pharmacokinetics, and Safety of CSL312 in Subjects With Hereditary Angioedema
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
October 29, 2018 (Actual)
Primary Completion Date
October 15, 2021 (Actual)
Study Completion Date
October 15, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Subjects are assigned to 1 of 2 or more groups in parallel for the duration of the study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double blind
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects with C1-INH HAE receiving buffer only
Arm Title
CSL312 (low)
Arm Type
Active Comparator
Arm Description
Subjects with C1-INH HAE receiving low dose CSL312
Arm Title
CSL312 (med)
Arm Type
Active Comparator
Arm Description
Subjects with C1-INH HAE receiving medium dose CSL312
Arm Title
CSL312 (high)
Arm Type
Active Comparator
Arm Description
Subjects with C1-INH HAE receiving high dose CSL312
Arm Title
CSL312 (med/high)
Arm Type
Active Comparator
Arm Description
Subjects with C1-INH HAE receiving medium/high dose CSL312
Intervention Type
Biological
Intervention Name(s)
Factor XIIa antagonist monoclonal antibody
Other Intervention Name(s)
CSL312
Intervention Description
Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Buffer without active ingredient
Primary Outcome Measure Information:
Title
The Mean Time Normalized Number of HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
Description
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
Time Frame
13 weeks
Secondary Outcome Measure Information:
Title
The Number of Responder Subjects With C1-INH HAE During Treatment Period 1
Description
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
Time Frame
13 weeks
Title
The Percentage of Responder Subjects With C1-INH HAE During Treatment Period 1
Description
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.
Time Frame
13 weeks
Title
The Number of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1
Time Frame
13 weeks
Title
The Percentage of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1
Time Frame
13 weeks
Title
The Number of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
Time Frame
13 weeks
Title
The Percentage of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
Time Frame
13 weeks
Title
The Mean Time-normalized Number of Mild, Moderate or Severe HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
Description
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
Time Frame
13 weeks
Title
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
Time Frame
13 weeks
Title
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
Time Frame
13 weeks
Title
Maximum Concentration (Cmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Time Frame
13 weeks
Title
Area Under the Concentration-time Curve in 1 Dosing Interval (AUC0-tau) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Time Frame
13 weeks
Title
Time of Maximum Concentration (Tmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Time Frame
13 weeks
Title
Terminal Elimination Half-life (T1/2) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Time Frame
13 weeks
Title
Clearance (CL/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Time Frame
13 weeks
Title
Volume of Distribution During the Elimination Phase (Vz/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Time Frame
13 weeks
Title
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
Description
Adverse events of special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.
Time Frame
13 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
CSL Behring LLC
Official's Role
Study Director
Facility Information:
Facility Name
Donald S. Levy
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Allergy & Asthma Clinical Research
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Immunoe Health Centers
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
Institute for Asthma and Allergy
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
The Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Pennsylvania State University
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
AARA Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Campbelltown Hospital
City
Campbelltown
State/Province
New South Wales
ZIP/Postal Code
2560
Country
Australia
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Allergy and Clinical Immunology McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 4K1
Country
Canada
Facility Name
Ottawa Allergy Research Corp
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1G 6C6
Country
Canada
Facility Name
Charité Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Universitätsklinikum Frankfurt Goethe-Universität
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Hautklinik und Poliklinik der Universitätsklinik Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
HZRM Hämophilie Zentrum Rhein Main GmbH
City
Mörfelden-Walldorf
ZIP/Postal Code
64546
Country
Germany
Facility Name
Barzilai University Medical Center
City
Ashkelon
ZIP/Postal Code
7830604
Country
Israel

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36326435
Citation
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.
Results Reference
derived
PubMed Identifier
35219377
Citation
Craig T, Magerl M, Levy DS, Reshef A, Lumry WR, Martinez-Saguer I, Jacobs JS, Yang WH, Ritchie B, Aygoren-Pursun E, Keith PK, Busse P, Feuersenger H, Pawaskar D, Jacobs I, Pragst I, Doyle MK. Prophylactic use of an anti-activated factor XII monoclonal antibody, garadacimab, for patients with C1-esterase inhibitor-deficient hereditary angioedema: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2022 Mar 5;399(10328):945-955. doi: 10.1016/S0140-6736(21)02225-X. Epub 2022 Feb 24.
Results Reference
derived

Learn more about this trial

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

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