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

Hereditary Angioedema Types I and II Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01912456
• Other study ID #: CSL830_3001
• Secondary ID: 2013-000916-10
• Status: Completed
• Phase: Phase 3
• Start date: January 2014
• Est. completion date: October 2015

Study information

• Verified date: January 2021
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema Types I and II

Intervention

Biological:
• Low-volume C1-esterase inhibitor

• Higher-volume C1-esterase inhibitor

• Low-volume placebo

• Higher-volume placebo

Locations

Country	Name	City	State
Australia	Study Site	Campbelltown	New South Wales
Canada	Study Site	Hamilton	Ontario
Canada	Study Site	Ottawa	Ontario
Canada	Study Site	Quebec
Canada	Study Site	Toronto	Ontario
Czechia	Study Site	Hradec Kralove
Czechia	Study Site	Plzen
Hungary	Study Site	Budapest
Israel	Study Site	Tel Aviv
Israel	Study Site	Tel Hashomer
Italy	Study Site	Catania
Italy	Study Site	Palermo
Romania	Study Site	Cluj Napoca
Romania	Study Site	Mures
Spain	Study Site	Barcelona
Spain	Study Site	Madrid
Spain	Study Site	Madrid
Spain	Study Site	Valencia
United Kingdom	Study Site	Brighton
United Kingdom	Study Site	London
United States	Study Site	Bell Gardens	California
United States	Study Site	Birmingham	Alabama
United States	Study Site	Boston	Massachusetts
United States	Study Site	Chevy Chase	Maryland
United States	Study Site	Cincinnati	Ohio
United States	Study Site	Colorado Springs	Colorado
United States	Study Site	Columbus	Ohio
United States	Study Site	Dallas	Texas
United States	Study Site	Hershey	Pennsylvania
United States	Study Site	La Jolla	California
United States	Study Site	Lake Oswego	Oregon
United States	Study Site	Orange	California
United States	Study Site	Richmond	Virginia
United States	Study Site	Scottsdale	Arizona
United States	Study Site	Spokane	Washington
United States	Study Site	Toledo	Ohio
United States	Study Site	Tulsa	Oklahoma
United States	Study Site	Virginia Beach	Virginia
United States	Study Site	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Hungary,  Israel,  Italy,  Romania,  Spain,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	During the treatment phase, up to 28 weeks.
Secondary	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%.	During the treatment phase, up to 28 weeks.
Secondary	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	During the treatment phase, up to 28 weeks.
Secondary	Percentage of Subjects With Adverse Events (AEs) Within 24 Hours of C1-esterase Inhibitor or Placebo Administration		Within 24 hours of C1-esterase inhibitor or placebo administration.
Secondary	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.	During the treatment phase, up to 32 weeks.
Secondary	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.	During the treatment phase, up to 32 weeks.
Secondary	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.	During the treatment phase, up to 32 weeks.