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

Primary Purpose

Hereditary Angioedema

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
CSL312
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

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Clinical Research Center of Alabama
  • Research Solutions of Arizona
  • Medical Research of Arizona
  • Little Rock Allergy & Asthma Clinic
  • Donald S. Levy M.D.
  • Raffi Tachdjian MD, Inc.
  • Allergy & Asthma Clinical Research
  • Institute for Asthma and Allergy PC
  • Bernstein Clinical Research Center, LLC
  • PennState Health Milton S. Hershey Medical Center
  • AARA Research Center
  • Campbelltown Hospital / Western Sydney University
  • The Alfred Hospital
  • Fiona Stanley Hospital, Department of Clinical Immunology
  • University of Alberta - Research Transition Facility
  • McMaster University
  • Ottawa Allergy Research Corp
  • Gordon Sussman Clinical Research
  • Montreal Clinical Research Institute
  • University hospital St. Anna Ustav klinicke imunologie a alergologie, Fakultní nemocnice u sv. Anny v Brně
  • University Hospital Motol
  • Charité - Universitätsmedizin Berlin
  • Universitätsklinikum Frankfurt
  • Johannes Gutenberg-Universität KöR, Hautklinik und Poliklinik der Universitätsmedizin, Clinical Research Center
  • HZRM Haemophilie Zentrum Rhein Main GmbH
  • The University of Hong Kong, Queen Mary Hospital
  • Semmelweis Egyetem Altalanos Orvostudományi Kar Belgyógyászati és Hematológiai Klinika
  • Barzilai University Medical Center
  • Koga Community Hospital
  • Mie University Hospital
  • Juntendo University Hospital
  • Saitama Medical Center
  • St. Marianna University School of Medicine Hospital
  • Clover Hospital
  • Saiyu Soka Hospital
  • National Hospital Organization Disaster Medical Center
  • Saga University Hospital
  • Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital
  • Amsterdam UMC, location AMC
  • Auckland City Hospital
  • NRC Institute of Immunology FMBA Russia
  • Hospital Universitari General de La Vall d'Hebron
  • Hospital Gregorio Marañón, Servicio de Alergia
  • Taichung Veterans General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CSL312

Arm Description

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

Outcomes

Primary Outcome Measures

Number of subjects with treatment emergent adverse events (TEAEs)
Percentage of subjects with TEAEs
TEAEs rates per injection
TEAEs rates per subject year

Secondary Outcome Measures

The time-normalized number (per month and year) of Hereditary Angioedema (HAE attacks) for the entire study
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
The time-normalized number (per month and year) of HAE attacks requiring on-demand treatment in subjects on treatment
The time-normalized number (per month and year) of moderate and/or severe HAE attacks in subjects on treatment
Number and percentage of subjects rating their response to therapy as good or excellent
The number and percentage of subjects experiencing TEAEs
The number and percentage of subjects experiencing adverse events of special interest (AESIs)
The number and percentage of subjects experiencing serious adverse events (SAEs), including deaths
The number and percentage of subjects experiencing CSL312 induced anti-CSL312 antibodies

Full Information

First Posted
February 1, 2021
Last Updated
October 12, 2023
Sponsor
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT04739059
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 29, 2021 (Actual)
Primary Completion Date
November 2025 (Anticipated)
Study Completion Date
November 2025 (Anticipated)

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 phase 3b study will evaluate long-term safety and efficacy of CSL312 (also known as garadacimab) when administered subcutaneously (SC)

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 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
171 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CSL312
Arm Type
Experimental
Arm Description
Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody administered subcutaneously
Intervention Type
Biological
Intervention Name(s)
CSL312
Other Intervention Name(s)
Factor XIIa inhibitor monoclonal antibody, garadacimab
Intervention Description
Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody
Primary Outcome Measure Information:
Title
Number of subjects with treatment emergent adverse events (TEAEs)
Time Frame
Up to 45 months
Title
Percentage of subjects with TEAEs
Time Frame
Up to 45 months
Title
TEAEs rates per injection
Time Frame
Up to 45 months
Title
TEAEs rates per subject year
Time Frame
Up to 45 months
Secondary Outcome Measure Information:
Title
The time-normalized number (per month and year) of Hereditary Angioedema (HAE attacks) for the entire study
Time Frame
Up to 43 months
Title
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
Title
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
Title
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
Title
Number and percentage of subjects rating their response to therapy as good or excellent
Time Frame
Up to 43 months
Title
The number and percentage of subjects experiencing TEAEs
Time Frame
Up to 45 months
Title
The number and percentage of subjects experiencing adverse events of special interest (AESIs)
Time Frame
Up to 45 months
Title
The number and percentage of subjects experiencing serious adverse events (SAEs), including deaths
Time Frame
Up to 45 months
Title
The number and percentage of subjects experiencing CSL312 induced anti-CSL312 antibodies
Time Frame
Up to 45 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Research Center of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Research Solutions of Arizona
City
Litchfield Park
State/Province
Arizona
ZIP/Postal Code
85340
Country
United States
Facility Name
Medical Research of Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
Little Rock Allergy & Asthma Clinic
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Donald S. Levy M.D.
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Raffi Tachdjian MD, Inc.
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Allergy & Asthma Clinical Research
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Institute for Asthma and Allergy PC
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Bernstein Clinical Research Center, LLC
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45236
Country
United States
Facility Name
PennState Health Milton S. Hershey Medical Center
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 / Western Sydney University
City
Campbelltown
State/Province
New South Wales
ZIP/Postal Code
2560
Country
Australia
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Fiona Stanley Hospital, Department of Clinical Immunology
City
Murdoch
State/Province
West Australia
ZIP/Postal Code
6150
Country
Australia
Facility Name
University of Alberta - Research Transition Facility
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
Ottawa Allergy Research Corp
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 1E4
Country
Canada
Facility Name
Gordon Sussman Clinical Research
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3B 3S6
Country
Canada
Facility Name
Montreal Clinical Research Institute
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2W 1R7
Country
Canada
Facility Name
University hospital St. Anna Ustav klinicke imunologie a alergologie, Fakultní nemocnice u sv. Anny v Brně
City
Brno
ZIP/Postal Code
65691
Country
Czechia
Facility Name
University Hospital Motol
City
Praha 5
ZIP/Postal Code
150 06
Country
Czechia
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Universitätsklinikum Frankfurt
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Johannes Gutenberg-Universität KöR, Hautklinik und Poliklinik der Universitätsmedizin, Clinical Research Center
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
HZRM Haemophilie Zentrum Rhein Main GmbH
City
Mörfelden-Walldorf
ZIP/Postal Code
64546
Country
Germany
Facility Name
The University of Hong Kong, Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Semmelweis Egyetem Altalanos Orvostudományi Kar Belgyógyászati és Hematológiai Klinika
City
Budapest
ZIP/Postal Code
1088
Country
Hungary
Facility Name
Barzilai University Medical Center
City
Ashkelon
ZIP/Postal Code
7830604
Country
Israel
Facility Name
Koga Community Hospital
City
Shizuoka
State/Province
Daikakuji Yaizu-shi
ZIP/Postal Code
425-0088
Country
Japan
Facility Name
Mie University Hospital
City
Mie
State/Province
Edobashi, Tsu-shi
ZIP/Postal Code
Edobashi, Tsu-shi
Country
Japan
Facility Name
Juntendo University Hospital
City
Tokyo
State/Province
Hongo Bunkyo-ku
ZIP/Postal Code
113-8431
Country
Japan
Facility Name
Saitama Medical Center
City
Saitama
State/Province
Kamoda Kawagoe-shi
ZIP/Postal Code
350-8550
Country
Japan
Facility Name
St. Marianna University School of Medicine Hospital
City
Kanagawa
State/Province
Kawasaki-shi
ZIP/Postal Code
216-8511
Country
Japan
Facility Name
Clover Hospital
City
Kanagawa
State/Province
Kugenumaishigami, Fujisawa-shi
ZIP/Postal Code
251-0025
Country
Japan
Facility Name
Saiyu Soka Hospital
City
Saitama
State/Province
Matsubara Soka-shi
ZIP/Postal Code
340-0041
Country
Japan
Facility Name
National Hospital Organization Disaster Medical Center
City
Tokyo
State/Province
Midoricho, Tachikawa-shi
ZIP/Postal Code
190-0014
Country
Japan
Facility Name
Saga University Hospital
City
Saga
State/Province
Nebeshima, Saga-shi
ZIP/Postal Code
849-8501
Country
Japan
Facility Name
Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital
City
Miyakojima-ku
State/Province
Osaka-shi
ZIP/Postal Code
534-0021
Country
Japan
Facility Name
Amsterdam UMC, location AMC
City
Amsterdam
ZIP/Postal Code
1105
Country
Netherlands
Facility Name
Auckland City Hospital
City
Grafton
State/Province
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Facility Name
NRC Institute of Immunology FMBA Russia
City
Moscow
ZIP/Postal Code
115522
Country
Russian Federation
Facility Name
Hospital Universitari General de La Vall d'Hebron
City
Barcelona
ZIP/Postal Code
8035
Country
Spain
Facility Name
Hospital Gregorio Marañón, Servicio de Alergia
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Taichung Veterans General Hospital
City
Taichung City
ZIP/Postal Code
407
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing 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.

Learn more about this trial

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

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