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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03712228




Registration number
NCT03712228
Ethics application status
Date submitted
17/10/2018
Date registered
19/10/2018
Date last updated
23/07/2019

Titles & IDs
Public title
A Study to Investigate CSL312 in Subjects With Hereditary Angioedema (HAE)
Scientific title
A Multicenter, Randomized, Placebo-controlled, Parallel-arm Study to Investigate the Efficacy, Pharmacokinetics, and Safety of CSL312 in Subjects With Hereditary Angioedema
Secondary ID [1] 0 0
CSL312_2001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hereditary Angioedema 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Factor XIIa antagonist monoclonal antibody
Treatment: Drugs - Placebo

Placebo Comparator: Placebo - Subjects with C1-INH HAE receiving buffer only

Active Comparator: CSL312 (low) - Subjects with C1-INH HAE receiving low dose CSL312

Active Comparator: CSL312 (med) - Subjects with C1-INH HAE receiving medium dose CSL312

Active Comparator: CSL312 (high) - Subjects with C1-INH HAE receiving high dose CSL312

Active Comparator: CSL312 (med/high) - Subjects with C1-INH HAE receiving medium/high dose CSL312

Active Comparator: CSL312-F - Subjects with FXII or plasminogen mutation (FXII/PLG) HAE receiving CSL312


Other interventions: Factor XIIa antagonist monoclonal antibody
Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use

Treatment: Drugs: Placebo
Buffer without active ingredient

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time normalized number of HAE attacks
Timepoint [1] 0 0
13 weeks
Secondary outcome [1] 0 0
The number of responder subjects and HAE attack-free 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
Timepoint [1] 0 0
13 weeks
Secondary outcome [2] 0 0
The percentage of responder subjects and HAE attack-free 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.
Timepoint [2] 0 0
13 weeks
Secondary outcome [3] 0 0
The number of mild, moderate or severe HAE attacks, as well as mild, moderate or severe HAE attacks treated with on-demand HAE medication, in subjects with C1-INH HAE during Treatment Period 1
Timepoint [3] 0 0
13 weeks
Secondary outcome [4] 0 0
The time-normalized number of mild, moderate or severe HAE attacks, as well as mild, moderate or severe HAE attacks treated with on-demand HAE medication, in subjects with C1-INH HAE during Treatment Period 1
Timepoint [4] 0 0
13 weeks
Secondary outcome [5] 0 0
The percentage of mild, moderate or severe HAE attacks, as well as mild, moderate or severe HAE attacks treated with on-demand HAE medication, in subjects with C1-INH HAE during Treatment Period 1
Timepoint [5] 0 0
13 weeks
Secondary outcome [6] 0 0
Maximum concentration (Cmax) of CSL312 in subjects with C1-INH HAE during Treatment Period 1
Timepoint [6] 0 0
13 weeks
Secondary outcome [7] 0 0
Area under the concentration-time curve in 1 dosing interval (AUC0-tau) of CSL312 in subjects with C1-INH HAE during Treatment Period 1
Timepoint [7] 0 0
13 weeks
Secondary outcome [8] 0 0
Time of maximum concentration (Tmax) of CSL312 in subjects with C1-INH HAE during Treatment Period 1
Timepoint [8] 0 0
13 weeks
Secondary outcome [9] 0 0
Terminal elimination half-life (T1/2) of CSL312 in subjects with C1-INH HAE during Treatment Period 1
Timepoint [9] 0 0
13 weeks
Secondary outcome [10] 0 0
Total systemic clearance (CLtot) of CSL312 in subjects with C1-INH HAE during Treatment Period 1
Timepoint [10] 0 0
13 weeks
Secondary outcome [11] 0 0
Volume of distribution during the elimination phase (Vz) of CSL312 in subjects with C1-INH HAE during Treatment Period 1
Timepoint [11] 0 0
13 weeks
Secondary outcome [12] 0 0
The number of subjects with C1-INH HAE with adverse events, serious adverse events, adverse events of special interest, injection site reactions, inhibitory antibodies to CSL312 during Treatment Period 1 - Special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.
Timepoint [12] 0 0
13 weeks
Secondary outcome [13] 0 0
The percentage of subjects with C1-INH HAE with adverse events, serious adverse events, adverse events of special interest, injection site reactions, inhibitory antibodies to CSL312 during Treatment Period 1 - Special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.
Timepoint [13] 0 0
13 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Campbelltown Hospital - Campbelltown
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Canada
State/province [10] 0 0
Alberta
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Germany
State/province [12] 0 0
Berlin
Country [13] 0 0
Germany
State/province [13] 0 0
Frankfurt
Country [14] 0 0
Germany
State/province [14] 0 0
Mainz
Country [15] 0 0
Germany
State/province [15] 0 0
Mörfelden-Walldorf
Country [16] 0 0
Israel
State/province [16] 0 0
Ashkelon

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
CSL Behring
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03712228
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
CSL Behring LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Registration Coordinator
Address 0 0
Country 0 0
Phone 0 0
610.878.4000
Fax 0 0
Email 0 0
clinicaltrials@cslbehring.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03712228