Hereditary Angioedema Types I and IIPhase 1/2NCT01576523
A Study to Evaluate the Clinical Pharmacology and Safety of C1-esterase Inhibitor Administered by the Subcutaneous Route
A Phase 1/2 study testing C1-esterase inhibitor - single intravenous dose, C1-esterase inhibitor - subcutaneous low dose and C1-esterase inhibitor - subcutaneous medium dose in people with Hereditary Angioedema Types I and II, run by CSL Behring at 8 sites in 2 countries.
Trial summary
The aim of the study is to assess what happens to C1-esterase inhibitor that is administered under the skin of subjects with hereditary angioedema. Three different dosing regimens of C1-esterase inhibitor will be assessed. Each subject will be assigned to receive 2 of the 3 dosing regimens, each for 4 weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Angioedema Types I and II
- What is being tested?
- C1-esterase inhibitor - single intravenous dose, C1-esterase inhibitor - subcutaneous low dose and C1-esterase inhibitor - subcutaneous medium dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Apr 2012to Dec 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females aged 18 years or older.
- Laboratory-confirmed hereditary angioedema type I or II.
- Less than two hereditary angioedema attacks per month in the last three months.
- Body weight of 50.0 kg to 110.0 kg.
Who cannot join
- Receiving prophylactic C1-esterase inhibitor therapy.
- Received C1-esterase inhibitor, ecallantide, icatibant or any blood products for the prevention or treatment of hereditary angioedema within 7 days before the screening visit.
- Intends to use recombinant C1-esterase inhibitor or fresh frozen plasma for the acute treatment of hereditary angioedema during the study.
- Received androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 30 days before the screening visit.
- 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.
- Known or suspected hypersensitivity to the study product, or to any excipients of the study product.
- Pregnancy or lactation.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States5 sites
Study Site
Atlanta, Georgia, 30342
Study Site
Chevy Chase, Maryland, 20815
Study Site
Cincinnati, Ohio, 45231
Study Site
Hershey, Pennsylvania, 19108
Study Site
Toledo, Ohio, 43617
Germany3 sites
Study Site
Berlin, 10117
Study Site
Frankfurt, 60596
Study Site
Mainz, 55101
About this study
Official title: An Open-label, Cross-over, Dose-ranging Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of the Subcutaneous Administration of a Human Plasma-derived C1-esterase Inhibitor in Subjects With Hereditary Angioedema
The aim of the study is to assess what happens to C1-esterase inhibitor that is administered under the skin of subjects with hereditary angioedema. Three different dosing regimens of C1-esterase inhibitor will be assessed. Each subject will be assigned to receive 2 of the 3 dosing regimens, each for 4 weeks. The activity and concentration of C1-esterase inhibitor in the blood will be measured during each 4-week period. The study will also examine how well C1-esterase inhibitor administered under the skin is tolerated by the subjects.
- Conditions
- Hereditary Angioedema Types I and II
- Being tested
- C1-esterase inhibitor - single intravenous dose, C1-esterase inhibitor - subcutaneous low dose, C1-esterase inhibitor - subcutaneous medium dose, C1-esterase inhibitor - subcutaneous high dose
- Medical subject headings
- Hereditary Angioedema Types I and II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C1-esterase inhibitor - single intravenous doseBiological
A single intravenous dose of C1-esterase inhibitor (Berinert) at 20 units per kg body weight will be administered to all subjects prior to receiving the first dose of subcutaneous C1-esterase inhibitor.
C1-esterase inhibitor - subcutaneous low doseBiological
A low dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.
C1-esterase inhibitor - subcutaneous medium doseBiological
A medium dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.
C1-esterase inhibitor - subcutaneous high doseBiological
A high dose of C1-esterase inhibitor will administered subcutaneously twice a week for four weeks.
| Study group | Role | What they receive |
|---|---|---|
| Low, then medium, C1-esterase inhibitor dose | Experimental | Not described Receives: Biological: C1-esterase inhibitor - single intravenous dose; Biological: C1-esterase inhibitor - subcutaneous low dose; Biological: C1-esterase inhibitor - subcutaneous medium dose |
| Medium, then low, C1-esterase inhibitor dose | Experimental | Not described Receives: Biological: C1-esterase inhibitor - single intravenous dose; Biological: C1-esterase inhibitor - subcutaneous low dose; Biological: C1-esterase inhibitor - subcutaneous medium dose |
| Medium, then high, C1-esterase inhibitor dose | Experimental | Not described Receives: Biological: C1-esterase inhibitor - single intravenous dose; Biological: C1-esterase inhibitor - subcutaneous medium dose; Biological: C1-esterase inhibitor - subcutaneous high dose |
| Low, then high, C1-esterase inhibitor dose | Experimental | Not described Receives: Biological: C1-esterase inhibitor - single intravenous dose; Biological: C1-esterase inhibitor - subcutaneous low dose; Biological: C1-esterase inhibitor - subcutaneous high dose |
| High, then low, C1-esterase inhibitor dose | Experimental | Not described Receives: Biological: C1-esterase inhibitor - single intravenous dose; Biological: C1-esterase inhibitor - subcutaneous low dose; Biological: C1-esterase inhibitor - subcutaneous high dose |
| High, then medium, C1-esterase inhibitor dose | Experimental | Not described Receives: Biological: C1-esterase inhibitor - single intravenous dose; Biological: C1-esterase inhibitor - subcutaneous medium dose; Biological: C1-esterase inhibitor - subcutaneous high dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modeled C1-esterase Inhibitor Functional Activity Trough Level
Mean trough C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens, based on modeling and simulation
Measured: at the fourth week of each dosing regimen
Secondary outcomes (6)
As-observed C1-esterase Inhibitor Functional Activity Trough Level
Mean trough C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens
Measured: during the last week of 4-week dose regimen
C1-esterase Inhibitor Concentration Trough Level
Mean trough C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens
Measured: during the last week of 4-week dose regimen
C4 Concentration Trough Level
Mean trough C4 concentration of the low, medium and high subcutaneous dose regimens
Measured: during the last week of 4-week dose regimen
Change From Baseline in C1-esterase Inhibitor Functional Activity
Mean change from baseline of C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens
Measured: Baseline and during the last week of 4-week dose regimen
Change From Baseline in C1-esterase Inhibitor Concentration
Mean change from baseline of C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens
Measured: Baseline and during the last week of 4-week dose regimen
Change From Baseline in C4 Concentration
Mean change from baseline of C4 concentration of the low, medium and high subcutaneous dose regimens
Measured: Baseline and during the last week of 4-week dose regimen
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2012 (estimated)
- Study startApr 2012
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary Angioedema Types I and IIStudies of the same condition, open and under way.
- More trials run by CSL BehringThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Global Clinical Program Director, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01576523
- Sponsor's protocol ID
- CSL830_2001
- Other IDs
- 2011-005013-36
- Status last verified
- Jan 2021
- First submitted
- 10 Apr 2012
- Last updated
- 1 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Zuraw BL, Cicardi M, Longhurst HJ, Bernstein JA, Li HH, Magerl M, Martinez-Saguer I, Rehman SM, Staubach P, Feuersenger H, Parasrampuria R, Sidhu J, Edelman J, Craig T. Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1-inhibitor concentrate. Allergy. 2015 Oct;70(10):1319-28. doi: 10.1111/all.12658. Epub 2015 Aug 11.
PubMed 26016741
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Cross-over, Dose-ranging Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of the Subcutaneous Administration of a Human Plasma-derived C1-esterase Inhibitor in Subjects With Hereditary Angioedema
- ClinicalTrials.gov ID
- NCT01576523
- Acronym / sponsor ID
- CSL830_2001
- Conditions
- Hereditary Angioedema Types I and II
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- Apr 2012
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 12 Apr 2012 (estimated)
- Results
- Posted 1 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to assess what happens to C1-esterase inhibitor that is administered under the skin of subjects with hereditary angioedema. Three different dosing regimens of C1-esterase inhibitor will be assessed. Each subject will be assigned to receive 2 of the 3 dosing regimens, each for 4 weeks. The activity and concentration of C1-esterase inhibitor in the blood will be measured during each 4-week period. The study will also examine how well C1-esterase inhibitor administered under the skin is tolerated by the subjects.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Low, then medium, C1-esterase inhibitor dose | Experimental | Biological: C1-esterase inhibitor - single intravenous dose, Biological: C1-esterase inhibitor - subcutaneous low dose, Biological: C1-esterase inhibitor - subcutaneous medium dose |
| Medium, then low, C1-esterase inhibitor dose | Experimental | Biological: C1-esterase inhibitor - single intravenous dose, Biological: C1-esterase inhibitor - subcutaneous low dose, Biological: C1-esterase inhibitor - subcutaneous medium dose |
| Medium, then high, C1-esterase inhibitor dose | Experimental | Biological: C1-esterase inhibitor - single intravenous dose, Biological: C1-esterase inhibitor - subcutaneous medium dose, Biological: C1-esterase inhibitor - subcutaneous high dose |
| Low, then high, C1-esterase inhibitor dose | Experimental | Biological: C1-esterase inhibitor - single intravenous dose, Biological: C1-esterase inhibitor - subcutaneous low dose, Biological: C1-esterase inhibitor - subcutaneous high dose |
| High, then low, C1-esterase inhibitor dose | Experimental | Biological: C1-esterase inhibitor - single intravenous dose, Biological: C1-esterase inhibitor - subcutaneous low dose, Biological: C1-esterase inhibitor - subcutaneous high dose |
| High, then medium, C1-esterase inhibitor dose | Experimental | Biological: C1-esterase inhibitor - single intravenous dose, Biological: C1-esterase inhibitor - subcutaneous medium dose, Biological: C1-esterase inhibitor - subcutaneous high dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males or females aged 18 years or older.
- Laboratory-confirmed hereditary angioedema type I or II.
- Less than two hereditary angioedema attacks per month in the last three months.
- Body weight of 50.0 kg to 110.0 kg.
Key exclusion criteria (7 listed)
- Receiving prophylactic C1-esterase inhibitor therapy.
- Received C1-esterase inhibitor, ecallantide, icatibant or any blood products for the prevention or treatment of hereditary angioedema within 7 days before the screening visit.
- Intends to use recombinant C1-esterase inhibitor or fresh frozen plasma for the acute treatment of hereditary angioedema during the study.
- Received androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 30 days before the screening visit.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| C1-esterase inhibitor - single intravenous doseA single intravenous dose of C1-esterase inhibitor (Berinert) at 20 units per kg body weight will be administered to all subjects prior to receiving the first dose of subcutaneous C1-esterase inhibitor. | Biological | High, then low, C1-esterase inhibitor dose, High, then medium, C1-esterase inhibitor dose, Low, then high, C1-esterase inhibitor dose, Low, then medium, C1-esterase inhibitor dose, Medium, then high, C1-esterase inhibitor dose, Medium, then low, C1-esterase inhibitor dose |
| C1-esterase inhibitor - subcutaneous low doseA low dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks. | Biological | High, then low, C1-esterase inhibitor dose, Low, then high, C1-esterase inhibitor dose, Low, then medium, C1-esterase inhibitor dose, Medium, then low, C1-esterase inhibitor dose |
| C1-esterase inhibitor - subcutaneous medium doseA medium dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks. | Biological | High, then medium, C1-esterase inhibitor dose, Low, then medium, C1-esterase inhibitor dose, Medium, then high, C1-esterase inhibitor dose, Medium, then low, C1-esterase inhibitor dose |
| C1-esterase inhibitor - subcutaneous high doseA high dose of C1-esterase inhibitor will administered subcutaneously twice a week for four weeks. | Biological | High, then low, C1-esterase inhibitor dose, High, then medium, C1-esterase inhibitor dose, Low, then high, C1-esterase inhibitor dose, Medium, then high, C1-esterase inhibitor dose |
Primary outcome
Modeled C1-esterase Inhibitor Functional Activity Trough Level
Time frame: at the fourth week of each dosing regimen
Mean trough C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens, based on modeling and simulation
6 secondary outcomes
As-observed C1-esterase Inhibitor Functional Activity Trough Level
Time frame: during the last week of 4-week dose regimen
C1-esterase Inhibitor Concentration Trough Level
Time frame: during the last week of 4-week dose regimen
C4 Concentration Trough Level
Time frame: during the last week of 4-week dose regimen
Change From Baseline in C1-esterase Inhibitor Functional Activity
Time frame: Baseline and during the last week of 4-week dose regimen
Change From Baseline in C1-esterase Inhibitor Concentration
Time frame: Baseline and during the last week of 4-week dose regimen
Change From Baseline in C4 Concentration
Time frame: Baseline and during the last week of 4-week dose regimen
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26016741Zuraw BL, Cicardi M, Longhurst HJ, Bernstein JA, Li HH, Magerl M, Martinez-Saguer I, Rehman SM, Staubach P, Feuersenger H, Parasrampuria R, Sidhu J, Edelman J, Craig T. Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1-inhibitor concentrate. Allergy. 2015 Oct;70(10):1319-28. doi: 10.1111/all.12658. Epub 2015 Aug 11.
Related trials for Hereditary Angioedema Types I and II
Enrolling by invitationPhase 2/3
Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema
Hereditary Angioedema, Hereditary Angioedema Type I
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Program Director study director
CSL Behring
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing C1-esterase inhibitor - single intravenous dose, C1-esterase inhibitor - subcutaneous low dose and C1-esterase inhibitor - subcutaneous medium dose in people with Hereditary Angioedema Types I and II, run by CSL Behring at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modeled C1-esterase Inhibitor Functional Activity Trough Level (time frame: at the fourth week of each dosing regimen). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01576523, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2021; AzTrials last refreshed its copy on 7 Nov 2026.