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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02316353




Registration number
NCT02316353
Ethics application status
Date submitted
10/12/2014
Date registered
12/12/2014
Date last updated
14/11/2018

Titles & IDs
Public title
A Study to Evaluate the Long-term Clinical Safety and Efficacy of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema
Scientific title
An Open-label, Randomized Study to Evaluate the Long-term Clinical Safety and Efficacy of Subcutaneous Administration of Human Plasma-derived C1-esterase Inhibitor in the Prophylactic Treatment of Hereditary Angioedema
Secondary ID [1] 0 0
2014-001054-42
Secondary ID [2] 0 0
CSL830_3002
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 - C1-esterase inhibitor

Experimental: C1-INH - low-volume dose - A low-volume dose of C1-INH will be administered subcutaneously twice a week for up to 52 weeks (up to 146 weeks extension period).

Experimental: C1-INH - medium-volume dose - A medium-volume dose of C1-INH will be administered subcutaneously twice a week for up to 52 weeks (up to 146 weeks extension period).


Other interventions: C1-esterase inhibitor


Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Person-time Incidence Rates (Subject Based) - Subject-based Analysis for Person-Time Incidence Rate = (the total number of subjects who experienced the event during the respective treatment) / (the sum of the date each subject experienced the event - the subject's start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: the Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.
Timepoint [1] 0 0
Up to 146 weeks.
Primary outcome [2] 0 0
The Person-time Incidence Rates (Event Based) - Event-based Analysis for Person-Time Incidence Rate = (the total number of events documented during the respective treatment) / (the sum of each subject's end date - the subject's start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.
Timepoint [2] 0 0
Up to 146 weeks.
Secondary outcome [1] 0 0
Percentage of Subjects Who Have Solicited Adverse Events (AEs) - The number of subjects having at least 1 solicited local AE during a treatment were divided by the number of subjects in the corresponding treatment. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.
Timepoint [1] 0 0
Up to 146 weeks
Secondary outcome [2] 0 0
Percentage of Injections Followed by At Least One Solicited Adverse Event - The percent of injections followed by at least one solicited adverse event. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. This was assessed across all participants, calculated as total number of events following injections / total number of injections across all participants, in each Arm.
Timepoint [2] 0 0
Up to 146 weeks
Secondary outcome [3] 0 0
Percentage of Subjects Who Become Seropositive for Human Immunodeficiency Virus (HIV-1/-2), Hepatitis B Virus, or Hepatitis C Virus. - Blood samples to be tested for HIV-1/-2, HBV, and HCV. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.
Timepoint [3] 0 0
Up to 146 weeks
Secondary outcome [4] 0 0
Percentage of Subjects Who Experience a Time-normalized HAE Attack Frequency of <1 HAE Attack Per 4-Week Period - The percentage of subjects with a time-normalized merged HAE attack frequency of <1 HAE attack per 4-week period. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL 830.
Timepoint [4] 0 0
Up to 146 weeks
Secondary outcome [5] 0 0
Percentage of Subjects Who Are Responders - A responder was defined as a subject with a = 50% reduction in the time-normalized number of HAE attacks on CSL830 relative to the time-normalized number of HAE attacks used to qualify for participation in the current study. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL830. Not all subjects in the ITT were available for this outcome measure.
Timepoint [5] 0 0
Up to 146 weeks

Eligibility
Key inclusion criteria
- Males or females aged 6 years or older.

- A confirmed diagnosis of HAE type I or II.

- HAE 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 first study visit: use of a stable regimen within 3 months of the first
study visit.
Minimum age
6 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Incurable malignancies.

- Any clinical condition that will interfere with the evaluation of C1-INH therapy.

- Clinically significant history of poor response to C1-esterase therapy for the
management of HAE.

- Suspected or confirmed diagnosis of acquired HAE or HAE with normal C1-INH.

- Inability to have HAE managed pharmacologically with on-demand treatment.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
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
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
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
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oklahoma
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
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
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
Czechia
State/province [13] 0 0
Plzen
Country [14] 0 0
Germany
State/province [14] 0 0
Hesse
Country [15] 0 0
Germany
State/province [15] 0 0
Berlin
Country [16] 0 0
Germany
State/province [16] 0 0
Frankfurt
Country [17] 0 0
Germany
State/province [17] 0 0
Mainz
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
Milano
Country [23] 0 0
Romania
State/province [23] 0 0
Cluj Napoca
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
Valencia
Country [26] 0 0
United Kingdom
State/province [26] 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 long-term safety of C1-esterase inhibitor (C1-INH) in
preventing hereditary angioedema (HAE) attacks when it is administered under the skin of
subjects with HAE. The safety of participating subjects will be assessed for up to 54 weeks.
The long-term efficacy of C1-INH will also be assessed. Each eligible subject will enter the
treatment phase, wherein subjects will be randomized to treatment with either low- or
medium-volume C1-INH. Subjects who have an insufficient treatment response during the study
will be given an opportunity to undergo a dose increase. The study aims to enroll eligible
subjects who completed study CSL830_3001 (NCT01912456). Subjects who did not participate in
study CSL830_3001 may also participate, if eligible and if space permits. Subjects from the
United States (US) who complete Treatment Period 2 will be allowed to participate in an
Extension Period. During the Extension Period participating US subjects will continue to
receive treatment with open-label CSL830 for up to an additional 88 weeks.
Trial website
https://clinicaltrials.gov/show/NCT02316353
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

Summary results
Other publications