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

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ClinicalTrials.gov Identifier: NCT03712228
Recruitment Status : Recruiting
First Posted : October 19, 2018
Last Update Posted : November 14, 2019
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Tracking Information
First Submitted Date  ICMJE October 17, 2018
First Posted Date  ICMJE October 19, 2018
Last Update Posted Date November 14, 2019
Actual Study Start Date  ICMJE October 29, 2018
Estimated Primary Completion Date December 14, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
Time normalized number of HAE attacks [ Time Frame: 13 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03712228 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2019)
  • The number of responder subjects and HAE attack-free subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 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 and HAE attack-free subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 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 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 [ Time Frame: 13 weeks ]
  • 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 [ Time Frame: 13 weeks ]
  • 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 [ Time Frame: 13 weeks ]
  • Maximum concentration (Cmax) of CSL312 in subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 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 [ Time Frame: 13 weeks ]
  • Time of maximum concentration (Tmax) of CSL312 in subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 13 weeks ]
  • Terminal elimination half-life (T1/2) of CSL312 in subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 13 weeks ]
  • Total systemic clearance (CLtot) of CSL312 in subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 13 weeks ]
  • Volume of distribution during the elimination phase (Vz) of CSL312 in subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 13 weeks ]
  • 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 [ Time Frame: 13 weeks ]
    Special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.
  • 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 [ Time Frame: 13 weeks ]
    Special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
  • The number of responder subjects and HAE attack-free subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 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 and HAE attack-free subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 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 person-time adjusted rate of HAE attack-free subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 13 weeks ]
  • 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 [ Time Frame: 13 weeks ]
  • 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 [ Time Frame: 13 weeks ]
  • 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 [ Time Frame: 13 weeks ]
  • Maximum concentration (Cmax) of CSL312 in subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 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 [ Time Frame: 13 weeks ]
  • Accumulation ratio (AR) of CSL312 in subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 13 weeks ]
  • Time of maximum concentration (Tmax) of CSL312 in subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 13 weeks ]
  • Terminal elimination half-life (T1/2) of CSL312 in subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 13 weeks ]
  • Total systemic clearance (CLtot) of CSL312 in subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 13 weeks ]
  • Volume of distribution during the elimination phase (Vz) of CSL312 in subjects with C1-INH HAE during Treatment Period 1 [ Time Frame: 13 weeks ]
  • 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 [ Time Frame: 13 weeks ]
    Special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.
  • 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 [ Time Frame: 13 weeks ]
    Special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Investigate CSL312 in Subjects With Hereditary Angioedema (HAE)
Official Title  ICMJE A Multicenter, Randomized, Placebo-controlled, Parallel-arm Study to Investigate the Efficacy, Pharmacokinetics, and Safety of CSL312 in Subjects With Hereditary Angioedema
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Subjects are assigned to 1 of 2 or more groups in parallel for the duration of the study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double blind
Primary Purpose: Prevention
Condition  ICMJE Hereditary Angioedema
Intervention  ICMJE
  • Biological: Factor XIIa antagonist monoclonal antibody
    Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
    Other Name: CSL312
  • Drug: Placebo
    Buffer without active ingredient
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Subjects with C1-INH HAE receiving buffer only
    Intervention: Drug: Placebo
  • Active Comparator: CSL312 (low)
    Subjects with C1-INH HAE receiving low dose CSL312
    Intervention: Biological: Factor XIIa antagonist monoclonal antibody
  • Active Comparator: CSL312 (med)
    Subjects with C1-INH HAE receiving medium dose CSL312
    Intervention: Biological: Factor XIIa antagonist monoclonal antibody
  • Active Comparator: CSL312 (high)
    Subjects with C1-INH HAE receiving high dose CSL312
    Intervention: Biological: Factor XIIa antagonist monoclonal antibody
  • Active Comparator: CSL312 (med/high)
    Subjects with C1-INH HAE receiving medium/high dose CSL312
    Intervention: Biological: Factor XIIa antagonist monoclonal antibody
  • Active Comparator: CSL312-F
    Subjects with FXII or plasminogen mutation (FXII/PLG) HAE receiving CSL312
    Intervention: Biological: Factor XIIa antagonist monoclonal antibody
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 17, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 15, 2021
Estimated Primary Completion Date December 14, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Registration Coordinator 610.878.4000 clinicaltrials@cslbehring.com
Listed Location Countries  ICMJE Australia,   Canada,   Germany,   Israel,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03712228
Other Study ID Numbers  ICMJE CSL312_2001
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  ICMJE
Plan to Share IPD: No
Responsible Party CSL Behring
Study Sponsor  ICMJE CSL Behring
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director CSL Behring LLC
PRS Account CSL Behring
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP