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

January 11, 2021 updated by: CSL Behring

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

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Campbelltown, New South Wales, Australia, 2560
        • Study Site
  • Canada
      • Quebec, Canada, G1V 4M6
        • Study Site
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • Study Site
      • Ottawa, Ontario, Canada, K1Y 4G2
        • Study Site
      • Toronto, Ontario, Canada, M4V 1R2
        • Study Site
  • Czechia
      • Hradec Kralove, Czechia, 50005
        • Study Site
      • Plzen, Czechia, 30460
        • Study Site
  • Hungary
      • Budapest, Hungary, 1125
        • Study Site
  • Israel
      • Tel Aviv, Israel, 64239
        • Study Site
      • Tel Hashomer, Israel, 52621
        • Study Site
  • Italy
      • Catania, Italy, 95123
        • Study Site
      • Palermo, Italy, 90146
        • Study Site
  • Romania
      • Cluj Napoca, Romania, 400139
        • Study Site
      • Mures, Romania, 540103
        • Study Site
  • Spain
      • Barcelona, Spain, 08035
        • Study Site
      • Madrid, Spain, 28007
        • Study Site
      • Madrid, Spain, 28046
        • Study Site
      • Valencia, Spain, 46026
        • Study Site
  • United Kingdom
      • Brighton, United Kingdom, BN2 5BE
        • Study Site
      • London, United Kingdom, E1 2ES
        • Study Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35209
        • Study Site
    • Arizona
      • Scottsdale, Arizona, United States, 85251
        • Study Site
    • California
      • Bell Gardens, California, United States, 90201
        • Study Site
      • La Jolla, California, United States, 92093
        • Study Site
      • Orange, California, United States, 92868
        • Study Site
      • Walnut Creek, California, United States, 94598
        • Study Site
    • Colorado
      • Colorado Springs, Colorado, United States, 80907
        • Study Site
    • Maryland
      • Chevy Chase, Maryland, United States, 20815
        • Study Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Study Site
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0563
        • Study Site
      • Columbus, Ohio, United States, 43235
        • Study Site
      • Toledo, Ohio, United States, 43617
        • Study Site
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • Study Site
    • Oregon
      • Lake Oswego, Oregon, United States, 97035
        • Study Site
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Study Site
    • Texas
      • Dallas, Texas, United States, 75231
        • Study Site
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Study Site
      • Virginia Beach, Virginia, United States, 23452
        • Study Site
    • Washington
      • Spokane, Washington, United States, 99204
        • Study Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Higher-volume placebo, then low-volume C1-esterase inhibitor
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.
Biological: Low-volume C1-esterase inhibitor
Biological: Higher-volume placebo
Experimental: Low-volume C1-esterase inhibitor, then higher-volume placebo
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.
Biological: Low-volume C1-esterase inhibitor
Biological: Higher-volume placebo
Experimental: Low-volume placebo, then higher-volume C1-esterase inhibitor
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.
Biological: Higher-volume C1-esterase inhibitor
Biological: Low-volume placebo
Experimental: Higher-volume C1-esterase inhibitor, then low-volume placebo
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.
Biological: Higher-volume C1-esterase inhibitor
Biological: Low-volume placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The Time-normalized Number of Hereditary Angioedema Attacks
Time Frame: During the treatment phase, up to 28 weeks.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Subjects With a ≥ 50% Reduction in the Number of Hereditary Angioedema Attacks by CSL830 Treatment
Time Frame: During the treatment phase, up to 28 weeks.
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.
Time-Normalized Number of Uses of Rescue Medication
Time Frame: During the treatment phase, up to 28 weeks.
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.
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.
Within 24 hours of C1-esterase inhibitor or placebo administration.
Percentage of Subjects With AEs or Other Specified Safety Events.
Time Frame: During the treatment phase, up to 32 weeks.
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.
Percentage of Subjects Experiencing Solicited AEs (Injection Site Reactions)
Time Frame: During the treatment phase, up to 32 weeks.
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.
Injections Resulting in Solicited AEs (Injection Site Reactions)
Time Frame: During the treatment phase, up to 32 weeks.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
CSL Behring

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 29, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 29, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 31, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 29, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CSL830_3001
  • 2013-000916-10 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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