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A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01912456
Recruitment Status : Completed
First Posted : July 31, 2013
Last Update Posted : July 28, 2017
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Tracking Information
First Submitted Date  ICMJE July 29, 2013
First Posted Date  ICMJE July 31, 2013
Last Update Posted Date July 28, 2017
Study Start Date  ICMJE January 2014
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 29, 2013)
The time-normalized number of hereditary angioedema attacks [ Time Frame: During the treatment phase, up to 32 weeks. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01912456 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2014)
  • Percentage of subjects with a ≥ 50% reduction in the number of hereditary angioedema attacks [ Time Frame: During the treatment phase, up to 32 weeks. ]
    The percentage of subjects with a ≥ 50% relative reduction in the time-normalized number of hereditary angioedema attacks during treatment with C1-esterase inhibitor compared with placebo
  • Number of uses of rescue medication [ Time Frame: During the treatment phase, up to 32 weeks. ]
    The time-normalized number of uses of rescue medication during treatment with C1-esterase inhibitor or placebo
  • Percentage of subjects with adverse events (AEs). [ Time Frame: Within 24 hours of C1-esterase inhibitor or placebo administration. ]
  • Percentage of subjects with AEs or other specified safety events. [ Time Frame: During the treatment phase, up to 32 weeks. ]
    The percentage of subjects with unsolicited AEs, serious AEs, or other specified safety events during treatment with C1-esterase inhibitor or placebo.
  • Percentage of subjects experiencing solicited AEs [ Time Frame: During the treatment phase, up to 32 weeks. ]
    The percentage of subjects experiencing solicited AEs (injection site reactions) during treatment with C1-esterase inhibitor or placebo.
  • Percentage of investigational product injections resulting in solicited AEs [ Time Frame: During the treatment phase, up to 32 weeks. ]
    The percentage of injections of C1-esterase inhibitor or placebo that result in solicited AEs (injection site reactions).
Original Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2013)
  • Proportion of subjects with a 50% reduction in the number of hereditary angioedema attacks [ Time Frame: During the treatment phase, up to 32 weeks. ]
    The percentage of subjects with a 50% relative reduction in the time-normalized number of hereditary angioedema attacks during treatment with C1-esterase inhibitor compared with placebo
  • Number of uses of rescue medication [ Time Frame: During the treatment phase, up to 32 weeks. ]
    The time-normalized number of uses of rescue medication during treatment with C1-esterase inhibitor or placebo
  • Proportion of subjects with any adverse events [ Time Frame: During or within 24 hours of C1-esterase or placebo administration. ]
    The percentage of subjects with any adverse events that begin within 24 hours of administration of C1-esterase inhibitor or placebo
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema
Official Title  ICMJE A Double-blind, Randomized, Placebo-controlled, Cross-over Study to Evaluate the Clinical Efficacy and Safety of Subcutaneous Administration of Human Plasma-derived C1-esterase Inhibitor in the Prophylactic Treatment of Hereditary Angioedema
Brief Summary The aim of this study is to assess the efficacy of C1-esterase inhibitor in preventing hereditary angioedema attacks when it is administered under the skin of subjects with hereditary angioedema. The safety of C1-esterase inhibitor will also be assessed. Each subject will enter a run-in period of up to 8-weeks. Subjects who complete the run-in period and who are eligible will then enter the treatment phase which comprises two sequential treatment periods. In the treatment phase, subjects will be randomized to one of four arms consisting of treatment with low- or higher-volume C1-esterase inhibitor in one treatment period and treatment with low- or higher-volume placebo in the other treatment period. The study will measure the number of hereditary angioedema attacks that subjects experience while receiving each treatment.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Hereditary Angioedema Types I and II
Intervention  ICMJE
  • Biological: Low-volume C1-esterase inhibitor
  • Biological: Higher-volume C1-esterase inhibitor
  • Biological: Low-volume placebo
  • Biological: Higher-volume placebo
Study Arms  ICMJE
  • Experimental: Higher-volume placebo, then low-volume C1-esterase inhibitor
    A higher-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks, then a low-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks.
    Interventions:
    • Biological: Low-volume C1-esterase inhibitor
    • Biological: Higher-volume placebo
  • Experimental: Low-volume C1-esterase inhibitor, then higher-volume placebo
    A low-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks, then a higher-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks.
    Interventions:
    • Biological: Low-volume C1-esterase inhibitor
    • Biological: Higher-volume placebo
  • Experimental: Low-volume placebo, then higher-volume C1-esterase inhibitor
    A low-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks then a higher-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks.
    Interventions:
    • Biological: Higher-volume C1-esterase inhibitor
    • Biological: Low-volume placebo
  • Experimental: Higher-volume C1-esterase inhibitor, then low-volume placebo
    A higher-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks, then a low-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks.
    Interventions:
    • Biological: Higher-volume C1-esterase inhibitor
    • Biological: Low-volume placebo
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: October 12, 2016)
90
Original Estimated Enrollment  ICMJE
 (submitted: July 29, 2013)
80
Actual Study Completion Date  ICMJE October 2015
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Run-In Period Inclusion Criteria:

  • Males or females aged 12 years or older.
  • A clinical diagnosis of hereditary angioedema type I or II.
  • Hereditary angioedema attacks over a consecutive 2-month period that required acute treatment, medical attention, or caused significant functional impairment.
  • For subjects who have used oral therapy for prophylaxis against HAE attacks within 3 months of Screening: use of a stable regimen within 3 months of Screening, with no plans to change.

Eligibility Criteria for Entering Treatment Period 1:

  • Laboratory confirmation of type I or type II hereditary angioedema, including C1-esterase inhibitor functional activity less than 50% AND C4 antigen level below the laboratory reference range.
  • No clinically significant abnormalities as assessed using laboratory parameters.
  • During participation in the run-in period, subjects must have experienced hereditary angioedema attacks that required acute treatment, required medical attention, or caused significant functional impairment.

Exclusion Criteria:

Run-In Period Exclusion Criteria:

  • History of clinical significant arterial or venous thrombosis, or current history of a clinically significant prothrombotic risk.
  • Incurable malignancies at screening.
  • Any clinical condition that will interfere with the evaluation of C1-esterase inhibitor therapy.
  • Clinically significant history of poor response to C1-esterase therapy for the management of hereditary angioedema.
  • Receiving therapy prohibited by the protocol, including medications for hereditary angioedema prophylaxis.
  • Female subjects who started taking or changed dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e., estrogen/progesterone-containing products) within 3 months prior to the screening visit.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Czechia,   Hungary,   Israel,   Italy,   Romania,   Spain,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01912456
Other Study ID Numbers  ICMJE CSL830_3001
2013-000916-10 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CSL Behring
Study Sponsor  ICMJE CSL Behring
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Global Clinical Program Director CSL Behring
PRS Account CSL Behring
Verification Date November 2015

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