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

Phase 3CompletedNCT01912456

CSL Behring90 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

Conditions

Hereditary Angioedema Types I and II

Interventions

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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.

Locations (39)

Study Site

Birmingham, Alabama, United States

Study Site

Scottsdale, Arizona, United States

Study Site

Bell Gardens, California, United States

Study Site

La Jolla, California, United States

Study Site

Orange, California, United States

Study Site

Outcomes

Primary Outcomes

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.

Time frame: During the treatment phase, up to 28 weeks.

Secondary Outcomes

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 frame: During the treatment phase, up to 28 weeks.

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

Time frame: During the treatment phase, up to 28 weeks.

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.

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.

Time frame: During the treatment phase, up to 32 weeks.

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.

Time frame: During the treatment phase, up to 32 weeks.

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.

Time frame: During the treatment phase, up to 32 weeks.