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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01912456




Registration number
NCT01912456
Ethics application status
Date submitted
29/07/2013
Date registered
31/07/2013
Date last updated
29/01/2021

Titles & IDs
Public title
A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema
Scientific title
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
Secondary ID [1] 0 0
2013-000916-10
Secondary ID [2] 0 0
CSL830_3001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hereditary Angioedema Types I and II 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
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Low-volume C1-esterase inhibitor
Other interventions - Higher-volume C1-esterase inhibitor
Other interventions - Low-volume placebo
Other interventions - Higher-volume placebo

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.

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.

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.

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.


Other interventions: Low-volume C1-esterase inhibitor


Other interventions: Higher-volume C1-esterase inhibitor


Other interventions: Low-volume placebo


Other interventions: Higher-volume placebo
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The Time-normalized Number of Hereditary Angioedema Attacks
Timepoint [1] 0 0
During the treatment phase, up to 28 weeks.
Secondary outcome [1] 0 0
Percentage of Subjects With a = 50% Reduction in the Number of Hereditary Angioedema Attacks by CSL830 Treatment
Timepoint [1] 0 0
During the treatment phase, up to 28 weeks.
Secondary outcome [2] 0 0
Time-Normalized Number of Uses of Rescue Medication
Timepoint [2] 0 0
During the treatment phase, up to 28 weeks.
Secondary outcome [3] 0 0
Percentage of Subjects With Adverse Events (AEs) Within 24 Hours of C1-esterase Inhibitor or Placebo Administration
Timepoint [3] 0 0
Within 24 hours of C1-esterase inhibitor or placebo administration.
Secondary outcome [4] 0 0
Percentage of Subjects With AEs or Other Specified Safety Events.
Timepoint [4] 0 0
During the treatment phase, up to 32 weeks.
Secondary outcome [5] 0 0
Percentage of Subjects Experiencing Solicited AEs (Injection Site Reactions)
Timepoint [5] 0 0
During the treatment phase, up to 32 weeks.
Secondary outcome [6] 0 0
Injections Resulting in Solicited AEs (Injection Site Reactions)
Timepoint [6] 0 0
During the treatment phase, up to 32 weeks.

Eligibility
Key inclusion criteria
Run-In Period

- 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.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Run-In Period

- 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.

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
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2015
Sample size
Target
Accrual to date
Final
90
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Study Site - 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
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
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
Oklahoma
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
Czechia
State/province [16] 0 0
Hradec Kralove
Country [17] 0 0
Czechia
State/province [17] 0 0
Plzen
Country [18] 0 0
Hungary
State/province [18] 0 0
Budapest
Country [19] 0 0
Israel
State/province [19] 0 0
Tel Aviv
Country [20] 0 0
Israel
State/province [20] 0 0
Tel Hashomer
Country [21] 0 0
Italy
State/province [21] 0 0
Catania
Country [22] 0 0
Italy
State/province [22] 0 0
Palermo
Country [23] 0 0
Romania
State/province [23] 0 0
Cluj Napoca
Country [24] 0 0
Romania
State/province [24] 0 0
Mures
Country [25] 0 0
Spain
State/province [25] 0 0
Barcelona
Country [26] 0 0
Spain
State/province [26] 0 0
Madrid
Country [27] 0 0
Spain
State/province [27] 0 0
Valencia
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Brighton
Country [29] 0 0
United Kingdom
State/province [29] 0 0
London

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

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01912456
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Global Clinical Program Director
Address 0 0
CSL Behring
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries