Back to resultsA Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema
Primary Purpose
Hereditary Angioedema Types I and II
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Low-volume C1-esterase inhibitor
Higher-volume C1-esterase inhibitor
Low-volume placebo
Higher-volume placebo
Sponsored by
About this trial
This is an interventional prevention trial for Hereditary Angioedema Types I and II focused on measuring Hereditary Angioedema
Eligibility Criteria
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.
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Higher-volume placebo, then low-volume C1-esterase inhibitor
Low-volume C1-esterase inhibitor, then higher-volume placebo
Low-volume placebo, then higher-volume C1-esterase inhibitor
Higher-volume C1-esterase inhibitor, then low-volume placebo
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
The Time-normalized Number of Hereditary Angioedema Attacks
The time normalized number of HAE attacks as reported by the investigator per subject was calculated as: The total number of HAE attacks per subject and per treatment period / length of stay of subject in treatment period (days), Where length of stay of subject in treatment period was calculated as: Date of last day of subject in treatment period - date of first day of Week 3 of subject in treatment period + 1.
Secondary Outcome Measures
Percentage of Subjects With a ≥ 50% Reduction in the Number of Hereditary Angioedema Attacks by CSL830 Treatment
The percentage reduction (%) in the time normalized number of HAE attacks was calculated as: 100 x [1 - (the time normalized number of HAE attacks when treated with CSL830) / (the time normalized number of HAE attacks when treated with placebo)]. A subject is classed as a responder if the percentage reduction is >= 50%.
Time-Normalized Number of Uses of Rescue Medication
The time-normalized number of uses of rescue medication during treatment with C1-esterase inhibitor or placebo
Percentage of Subjects With Adverse Events (AEs) Within 24 Hours of C1-esterase Inhibitor or Placebo Administration
Percentage of Subjects With AEs or Other Specified Safety Events.
The percentage of subjects experiencing the following during treatment with CSL830 and placebo: unsolicited AEs, serious AEs, suspected adverse drug reactions, increased risk scores for deep vein thrombosis and pulmonary embolism, thromboembolic events, inhibitory anti C1 INH antibodies, or clinically significant abnormalities in laboratory assessments.
Percentage of Subjects Experiencing Solicited AEs (Injection Site Reactions)
The percentage of subjects experiencing solicited local AEs (discomfort [eg, pain, burning], swelling, bruising, or itching at the investigational product injection site) during treatment with CSL830 and placebo.
Injections Resulting in Solicited AEs (Injection Site Reactions)
The rate/injection of injections of C1-esterase inhibitor or placebo that were followed by solicited local AEs (discomfort [eg, pain, burning], swelling, bruising, or itching at the investigational product injection site) during treatment with CSL830 and placebo. Rate/Injection = Number of events/number of injections.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01912456
Brief Title
A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema
Official 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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema Types I and II
Keywords
Hereditary Angioedema
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Higher-volume placebo, then low-volume C1-esterase inhibitor
Arm Type
Experimental
Arm Description
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.
Arm Title
Low-volume C1-esterase inhibitor, then higher-volume placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Low-volume placebo, then higher-volume C1-esterase inhibitor
Arm Type
Experimental
Arm Description
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.
Arm Title
Higher-volume C1-esterase inhibitor, then low-volume placebo
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Low-volume C1-esterase inhibitor
Intervention Type
Biological
Intervention Name(s)
Higher-volume C1-esterase inhibitor
Intervention Type
Biological
Intervention Name(s)
Low-volume placebo
Intervention Type
Biological
Intervention Name(s)
Higher-volume placebo
Primary Outcome Measure Information:
Title
The Time-normalized Number of Hereditary Angioedema Attacks
Description
The time normalized number of HAE attacks as reported by the investigator per subject was calculated as: The total number of HAE attacks per subject and per treatment period / length of stay of subject in treatment period (days), Where length of stay of subject in treatment period was calculated as: Date of last day of subject in treatment period - date of first day of Week 3 of subject in treatment period + 1.
Time Frame
During the treatment phase, up to 28 weeks.
Secondary Outcome Measure Information:
Title
Percentage of Subjects With a ≥ 50% Reduction in the Number of Hereditary Angioedema Attacks by CSL830 Treatment
Description
The percentage reduction (%) in the time normalized number of HAE attacks was calculated as: 100 x [1 - (the time normalized number of HAE attacks when treated with CSL830) / (the time normalized number of HAE attacks when treated with placebo)]. A subject is classed as a responder if the percentage reduction is >= 50%.
Time Frame
During the treatment phase, up to 28 weeks.
Title
Time-Normalized Number of Uses of Rescue Medication
Description
The time-normalized number of uses of rescue medication during treatment with C1-esterase inhibitor or placebo
Time Frame
During the treatment phase, up to 28 weeks.
Title
Percentage of Subjects With Adverse Events (AEs) Within 24 Hours of C1-esterase Inhibitor or Placebo Administration
Time Frame
Within 24 hours of C1-esterase inhibitor or placebo administration.
Title
Percentage of Subjects With AEs or Other Specified Safety Events.
Description
The percentage of subjects experiencing the following during treatment with CSL830 and placebo: unsolicited AEs, serious AEs, suspected adverse drug reactions, increased risk scores for deep vein thrombosis and pulmonary embolism, thromboembolic events, inhibitory anti C1 INH antibodies, or clinically significant abnormalities in laboratory assessments.
Time Frame
During the treatment phase, up to 32 weeks.
Title
Percentage of Subjects Experiencing Solicited AEs (Injection Site Reactions)
Description
The percentage of subjects experiencing solicited local AEs (discomfort [eg, pain, burning], swelling, bruising, or itching at the investigational product injection site) during treatment with CSL830 and placebo.
Time Frame
During the treatment phase, up to 32 weeks.
Title
Injections Resulting in Solicited AEs (Injection Site Reactions)
Description
The rate/injection of injections of C1-esterase inhibitor or placebo that were followed by solicited local AEs (discomfort [eg, pain, burning], swelling, bruising, or itching at the investigational product injection site) during treatment with CSL830 and placebo. Rate/Injection = Number of events/number of injections.
Time Frame
During the treatment phase, up to 32 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Program Director
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Study Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Study Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
Study Site
City
Bell Gardens
State/Province
California
ZIP/Postal Code
90201
Country
United States
Facility Name
Study Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Study Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Study Site
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Study Site
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Study Site
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Study Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Study Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267-0563
Country
United States
Facility Name
Study Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Facility Name
Study Site
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43617
Country
United States
Facility Name
Study Site
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Study Site
City
Lake Oswego
State/Province
Oregon
ZIP/Postal Code
97035
Country
United States
Facility Name
Study Site
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Study Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Study Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Study Site
City
Virginia Beach
State/Province
Virginia
ZIP/Postal Code
23452
Country
United States
Facility Name
Study Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Study Site
City
Campbelltown
State/Province
New South Wales
ZIP/Postal Code
2560
Country
Australia
Facility Name
Study Site
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
Study Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4G2
Country
Canada
Facility Name
Study Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4V 1R2
Country
Canada
Facility Name
Study Site
City
Quebec
ZIP/Postal Code
G1V 4M6
Country
Canada
Facility Name
Study Site
City
Hradec Kralove
ZIP/Postal Code
50005
Country
Czechia
Facility Name
Study Site
City
Plzen
ZIP/Postal Code
30460
Country
Czechia
Facility Name
Study Site
City
Budapest
ZIP/Postal Code
1125
Country
Hungary
Facility Name
Study Site
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Study Site
City
Tel Hashomer
ZIP/Postal Code
52621
Country
Israel
Facility Name
Study Site
City
Catania
ZIP/Postal Code
95123
Country
Italy
Facility Name
Study Site
City
Palermo
ZIP/Postal Code
90146
Country
Italy
Facility Name
Study Site
City
Cluj Napoca
ZIP/Postal Code
400139
Country
Romania
Facility Name
Study Site
City
Mures
ZIP/Postal Code
540103
Country
Romania
Facility Name
Study Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Study Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Study Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Study Site
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Study Site
City
Brighton
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
Facility Name
Study Site
City
London
ZIP/Postal Code
E1 2ES
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
28328347
Citation
Longhurst H, Cicardi M, Craig T, Bork K, Grattan C, Baker J, Li HH, Reshef A, Bonner J, Bernstein JA, Anderson J, Lumry WR, Farkas H, Katelaris CH, Sussman GL, Jacobs J, Riedl M, Manning ME, Hebert J, Keith PK, Kivity S, Neri S, Levy DS, Baeza ML, Nathan R, Schwartz LB, Caballero T, Yang W, Crisan I, Hernandez MD, Hussain I, Tarzi M, Ritchie B, Kralickova P, Guilarte M, Rehman SM, Banerji A, Gower RG, Bensen-Kennedy D, Edelman J, Feuersenger H, Lawo JP, Machnig T, Pawaskar D, Pragst I, Zuraw BL; COMPACT Investigators. Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor. N Engl J Med. 2017 Mar 23;376(12):1131-1140. doi: 10.1056/NEJMoa1613627.
Results Reference
result
PubMed Identifier
36326435
Citation
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.
Results Reference
derived
PubMed Identifier
31485239
Citation
Li HH, Zuraw B, Longhurst HJ, Cicardi M, Bork K, Baker J, Lumry W, Bernstein J, Manning M, Levy D, Riedl MA, Feuersenger H, Prusty S, Pragst I, Machnig T, Craig T; COMPACT Investigators. Subcutaneous C1 inhibitor for prevention of attacks of hereditary angioedema: additional outcomes and subgroup analysis of a placebo-controlled randomized study. Allergy Asthma Clin Immunol. 2019 Aug 28;15:49. doi: 10.1186/s13223-019-0362-1. eCollection 2019.
Results Reference
derived
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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
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