Hereditary AngioedemaPhase 2/3NCT00168103
Human C1 Esterase Inhibitor (C1-INH) in Subjects With Acute Abdominal or Facial Hereditary Angioedema (HAE) Attacks
A Phase 2/3 study testing C1 Esterase Inhibitor in people with Hereditary Angioedema, run by CSL Behring at 36 sites in 15 countries.
Trial summary
HAE is a rare disorder characterized by functional C1 esterase inhibitor deficiency. If not treated adequately, the acute attacks of HAE can be life-threatening and may even result in fatalities, especially in case of swelling of the larynx. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- C1 Esterase Inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 126 participants
- Where
- 36 sitesin 15 countries
- Study dates
- Jun 2005to Dec 2007
- Phase
- Phase 2/3
- 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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Documented congenital C1-INH deficiency
- Acute facial or abdominal HAE attack
Who cannot join
- Acquired angioedema
- Treatment with any other investigational drug within the last 30 days before study entry
- Treatment with any C1-INH concentrate within the previous 7 days
Trial locations and contacts
36 sites in 15 countries.
36 sites in 15 countries
United States17 sites
Study Site
Atlanta, Georgia, 30342
Study Site
Bellingham, Washington, 98225
Study Site
Boston, Massachusetts, 02115
Study Site
Chicago, Illinois, 60612
Study Site
Cincinnati, Ohio, 45231
Study Site
Dallas, Texas, 75230
Study Site
Eugene, Oregon, 97401
Study Site
Granada Hills, California, 91344
Study Site
Hershey, Pennsylvania, 17033
Study Site
Idaho Falls, Idaho, 83404
Study Site
Omaha, Nebraska, 68131
Study Site
Plymouth, Minnesota, 55411
Study Site
Rapid City, South Dakota, 57702
Study Site
Shreveport, Louisiana, 71130
Study Site
The Bronx, New York, 10461
Study Site
Tulsa, Oklahoma, 74133
Study Site
Weston, Florida, 33331
About this study
Official title: Human Pasteurized C1 Esterase Inhibitor Concentrate (CE1145) in Subjects With Congenital C1-INH Deficiency and Acute Abdominal or Facial HAE Attacks
HAE is a rare disorder characterized by functional C1 esterase inhibitor deficiency. If not treated adequately, the acute attacks of HAE can be life-threatening and may even result in fatalities, especially in case of swelling of the larynx. This clinical Phase 2/Phase 3 study was designed to provide clinically relevant data on dosing, efficacy and safety in subjects with HAE.
Read the detailed description
For each subject, only a single abdominal or facial attack was treated and evaluated. After receiving treatment, subjects were observed for a minimum of 4 hours, after which they could be discharged from the study center if they reported onset of symptom relief. Starting from 4 hours after treatment, subjects who reported insufficient or no symptom relief could receive a second dose of double-blind treatment (called "rescue medication") as follows: C1-INH 20 U/kg bw for subjects initially receiving placebo, C1-INH 10 U/kg bw for subjects initially receiving C1-INH 10 U/kg bw, and placebo for subjects initially receiving C1-INH 20 U/kg bw.
The study was defined to be successful if the primary outcome measure and at least one of the secondary outcome measures were met in the comparison between the C1-INH 20 U/kg bw group and the Placebo group.
- Conditions
- Hereditary Angioedema
- Being tested
- C1 Esterase Inhibitor, Placebo
- Keywords
- C1 Inhibitor, Hereditary angioedema, Acute HAE attack
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C1 Esterase InhibitorBiological
Also called Berinert, Berinert P, CE1145
Single application of C1-INH administered intravenously by slow injection or infusion at a recommended rate of 4mL/min.
PlaceboBiological
Also called Physiological saline solution
Single application of physiological saline solution equivalent to the volume calculated for subjects in the C1-INH 20 U/kg bw arm.
| Study group | Role | What they receive |
|---|---|---|
| C1-INH 10 U/kg bw | Experimental | 10 Units (U)/kg body weight (bw) dose Receives: Biological: C1 Esterase Inhibitor |
| C1-INH 20 U/kg bw | Experimental | 20 U/kg bw dose Receives: Biological: C1 Esterase Inhibitor |
| Placebo | Placebo comparator | Not described Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Start of Relief of Symptoms From HAE Attack
The start of symptom relief was determined by subject self-assessment. Time to start of symptom relief was set to 24 hours if the subject received rescue medication (blinded study medication, narcotic analgesics, antiemetics, open-label C1-INH, or fresh frozen plasma) at any time point after the start of study treatment but before start of relief.
Measured: Up to 24 h after start of study treatment
Secondary outcomes (2)
Number of Subjects With Worsened Intensity of Clinical HAE Symptoms
Includes any worsening of intensity of at least 1 of the HAE symptoms present at baseline. Routinely checked symptoms included pain, nausea, vomiting, cramps, and diarrhea.
Measured: Baseline and between 2 and 4 h after start of study treatment
Number of Vomiting Episodes
Measured: Within 4 h after start of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startJun 2005
- Primary completionOct 2007
- Study completionDec 2007
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 (4)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Program Director, Clinical R&D, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00168103
- Sponsor's protocol ID
- CE1145_3001
- Other IDs
- 2004-001186-17, 2004
- Status last verified
- Feb 2011
- First submitted
- 12 Sep 2005
- Last updated
- 31 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bernstein JA, Ritchie B, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz DS, Obtulowicz K, Reshef A, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Keinecke HO, Craig TJ. Hereditary angioedema: Validation of the end point time to onset of relief by correlation with symptom intensity. Allergy Asthma Proc. 2011 Jan-Feb;32(1):36-42. doi: 10.2500/aap.2011.32.3404.
PubMed 21262096Craig TJ, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz D, Obtulowicz K, Reshef A, Ritchie B, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Keinecke HO, Bernstein JA. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009 Oct;124(4):801-8. doi: 10.1016/j.jaci.2009.07.017. Epub 2009 Sep 19.
PubMed 19767078Craig TJ, Rojavin MA, Machnig T, Keinecke HO, Bernstein JA. Effect of time to treatment on response to C1 esterase inhibitor concentrate for hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2013 Sep;111(3):211-5. doi: 10.1016/j.anai.2013.06.021. Epub 2013 Jul 16.
PubMed 23987198Bernstein JA, Ritchie B, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz DS, Obtulowicz K, Reshef A, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Schindel F, Craig TJ. Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2010 Aug;105(2):149-54. doi: 10.1016/j.anai.2010.06.005.
PubMed 20674826
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Pasteurized C1 Esterase Inhibitor Concentrate (CE1145) in Subjects With Congenital C1-INH Deficiency and Acute Abdominal or Facial HAE Attacks
- ClinicalTrials.gov ID
- NCT00168103
- Acronym / sponsor ID
- CE1145_3001
- Conditions
- Hereditary Angioedema
- Keywords
- C1 Inhibitor, Hereditary angioedema, Acute HAE attack
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 126 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- Jun 2005
- Primary completion
- Oct 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 14 Sep 2005 (estimated)
- Results
- Posted 24 Aug 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HAE is a rare disorder characterized by functional C1 esterase inhibitor deficiency. If not treated adequately, the acute attacks of HAE can be life-threatening and may even result in fatalities, especially in case of swelling of the larynx. This clinical Phase 2/Phase 3 study was designed to provide clinically relevant data on dosing, efficacy and safety in subjects with HAE.
Detailed description
For each subject, only a single abdominal or facial attack was treated and evaluated. After receiving treatment, subjects were observed for a minimum of 4 hours, after which they could be discharged from the study center if they reported onset of symptom relief. Starting from 4 hours after treatment, subjects who reported insufficient or no symptom relief could receive a second dose of double-blind treatment (called "rescue medication") as follows: C1-INH 20 U/kg bw for subjects initially receiving placebo, C1-INH 10 U/kg bw for subjects initially receiving C1-INH 10 U/kg bw, and placebo for subjects initially receiving C1-INH 20 U/kg bw.
The study was defined to be successful if the primary outcome measure and at least one of the secondary outcome measures were met in the comparison between the C1-INH 20 U/kg bw group and the Placebo group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| C1-INH 10 U/kg bw | Experimental | Biological: C1 Esterase Inhibitor10 Units (U)/kg body weight (bw) dose |
| C1-INH 20 U/kg bw | Experimental | Biological: C1 Esterase Inhibitor20 U/kg bw dose |
| Placebo | Placebo comparator | Biological: Placebo |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Documented congenital C1-INH deficiency
- Acute facial or abdominal HAE attack
Key exclusion criteria (3 listed)
- Acquired angioedema
- Treatment with any other investigational drug within the last 30 days before study entry
- Treatment with any C1-INH concentrate within the previous 7 days
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 InhibitorAlso: Berinert, Berinert P, CE1145Single application of C1-INH administered intravenously by slow injection or infusion at a recommended rate of 4mL/min. | Biological | C1-INH 10 U/kg bw, C1-INH 20 U/kg bw |
| PlaceboAlso: Physiological saline solutionSingle application of physiological saline solution equivalent to the volume calculated for subjects in the C1-INH 20 U/kg bw arm. | Biological | Placebo |
Primary outcome
Time to Start of Relief of Symptoms From HAE Attack
Time frame: Up to 24 h after start of study treatment
The start of symptom relief was determined by subject self-assessment. Time to start of symptom relief was set to 24 hours if the subject received rescue medication (blinded study medication, narcotic analgesics, antiemetics, open-label C1-INH, or fresh frozen plasma) at any time point after the start of study treatment but before start of relief.
2 secondary outcomes
Number of Subjects With Worsened Intensity of Clinical HAE Symptoms
Time frame: Baseline and between 2 and 4 h after start of study treatment
Number of Vomiting Episodes
Time frame: Within 4 h after start of study treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21262096Bernstein JA, Ritchie B, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz DS, Obtulowicz K, Reshef A, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Keinecke HO, Craig TJ. Hereditary angioedema: Validation of the end point time to onset of relief by correlation with symptom intensity. Allergy Asthma Proc. 2011 Jan-Feb;32(1):36-42. doi: 10.2500/aap.2011.32.3404.
- Results publication: PubMed 19767078Craig TJ, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz D, Obtulowicz K, Reshef A, Ritchie B, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Keinecke HO, Bernstein JA. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009 Oct;124(4):801-8. doi: 10.1016/j.jaci.2009.07.017. Epub 2009 Sep 19.
- Derived from this study: PubMed 23987198Craig TJ, Rojavin MA, Machnig T, Keinecke HO, Bernstein JA. Effect of time to treatment on response to C1 esterase inhibitor concentrate for hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2013 Sep;111(3):211-5. doi: 10.1016/j.anai.2013.06.021. Epub 2013 Jul 16.
- Derived from this study: PubMed 20674826Bernstein JA, Ritchie B, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz DS, Obtulowicz K, Reshef A, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Schindel F, Craig TJ. Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2010 Aug;105(2):149-54. doi: 10.1016/j.anai.2010.06.005.
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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.
Program Director, Clinical R&D study director
CSL Behring
36 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing C1 Esterase Inhibitor in people with Hereditary Angioedema, run by CSL Behring at 36 sites in 15 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 2 inclusion and 3 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 31 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Russia, Bulgaria, Canada, Poland and 10 more countries. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 24 Aug 2010). 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?
Time to Start of Relief of Symptoms From HAE Attack (time frame: Up to 24 h after start of study treatment). 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 NCT00168103, which also lists 4 linked publications.
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 31 Mar 2015.