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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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).
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Person-time Incidence Rates (Subject Based)
Timepoint [1] 0 0
Up to 146 weeks.
Primary outcome [2] 0 0
The Person-time Incidence Rates (Event Based)
Timepoint [2] 0 0
Up to 146 weeks.
Secondary outcome [1] 0 0
Percentage of Subjects Who Have Solicited Adverse Events (AEs)
Timepoint [1] 0 0
Up to 146 weeks
Secondary outcome [2] 0 0
Percentage of Injections Followed by At Least One Solicited Adverse Event
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.
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
Timepoint [4] 0 0
Up to 146 weeks
Secondary outcome [5] 0 0
Percentage of Subjects Who Are Responders
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
Sex
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
31/12/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/09/2017
Sample size
Target
Accrual to date
Final
126
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/study/NCT02316353
Trial related presentations / publications
Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
Lumry WR, Zuraw B, Cicardi M, Craig T, Anderson J, Banerji A, Bernstein JA, Caballero T, Farkas H, Gower RG, Keith PK, Levy DS, Li HH, Magerl M, Manning M, Riedl MA, Lawo JP, Prusty S, Machnig T, Longhurst H; on behalf of the COMPACT Investigators. Long-term health-related quality of life in patients treated with subcutaneous C1-inhibitor replacement therapy for the prevention of hereditary angioedema attacks: findings from the COMPACT open-label extension study. Orphanet J Rare Dis. 2021 Feb 15;16(1):86. doi: 10.1186/s13023-020-01658-4. Erratum In: Orphanet J Rare Dis. 2021 Jul 28;16(1):329. doi: 10.1186/s13023-021-01975-2.
Levy DS, Farkas H, Riedl MA, Hsu FI, Brooks JP, Cicardi M, Feuersenger H, Pragst I, Reshef A. Long-term efficacy and safety of subcutaneous C1-inhibitor in women with hereditary angioedema: subgroup analysis from an open-label extension of a phase 3 trial. Allergy Asthma Clin Immunol. 2020 Feb 4;16:8. doi: 10.1186/s13223-020-0409-3. eCollection 2020.
Craig T, Zuraw B, Longhurst H, Cicardi M, Bork K, Grattan C, Katelaris C, Sussman G, Keith PK, Yang W, Hebert J, Hanzlikova J, Staubach-Renz P, Martinez-Saguer I, Magerl M, Aygoren-Pursun E, Farkas H, Reshef A, Kivity S, Neri S, Crisan I, Caballero T, Baeza ML, Hernandez MD, Li H, Lumry W, Bernstein JA, Hussain I, Anderson J, Schwartz LB, Jacobs J, Manning M, Levy D, Riedl M, Christiansen S, Feuersenger H, Pragst I, Mycroft S, Pawaskar D, Jacobs I; COMPACT Investigators. Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks. J Allergy Clin Immunol Pract. 2019 Jul-Aug;7(6):1793-1802.e2. doi: 10.1016/j.jaip.2019.01.054. Epub 2019 Feb 15.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02316353