Hereditary AngioedemaPhase 3NCT00289211
C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks
A Phase 3 study testing C1 esterase inhibitor [human] (C1INH-nf) in people with Hereditary Angioedema, run by Shire at 37 sites in United States.
Trial summary
The study objective was to determine the safety and efficacy of C1INH-nf for the treatment of acute HAE attacks. 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 [human] (C1INH-nf)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 83 participants
- Where
- 37 sitesUnited States
- Study dates
- 14 Mar 2005to 13 Apr 2007
- Phase
- Phase 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 HAE
- Normal C1q level
Who cannot join
- Low C1q level
- B-cell malignancy
- Presence of anti-C1INH autoantibody
- History of allergic reaction to C1INH or other blood products
- Narcotic addiction
- Current participation in any other investigational drug study or within the past 30 days
Show all 9Show fewer
- Participation in a C1 esterase inhibitor trial, or received blood or a blood product in the past 90 days
- Pregnancy or lactation
- Any clinically significant medical condition, such as renal failure, that in the opinion of the investigator would interfere with the subject's ability to participate in the study
Trial locations and contacts
37 sites in 1 country.
37 sites in 1 country
United States37 sites
Family Allergy and Asthma Center
Atlanta, Georgia, 30342
The Baton Rouge Clinic, AMC
Baton Rouge, Louisiana, 70808
Bernstein Clinical Research
Cincinnati, Ohio, 45231
Optimed Research
Columbus, Ohio, 43235
AARA Research Center
Dallas, Texas, 75231
Duke University Medical Center
Durham, North Carolina, 27710
Welborn Clinic Allergy and Immunology
Evansville, Indiana, 47713
Allergy Asthma and Immunology
Falmouth, Massachusetts, 02550
MeritCare Clinical Research
Fargo, North Dakota, 58122
Allergy and Asthma Center
Fort Lauderdale, Florida, 33334
University of Texas Medical Branch
Galveston, Texas, 77555-1083
Allergy Partners of the Upstate
Greenville, South Carolina, 29615
Penn State University
Hershey, Pennsylvania, 17033
Clinical Research Consultants, Inc
Hoover, Alabama, 35216
Baylor College of Medicine
Houston, Texas, 77030
University of Iowa Hospital and Clinic
Iowa City, Iowa, 52242
Allergy Asthma and Dermatology Research Center
Lake Oswego, Oregon, 97035
Nevada Access to Research and Education Society
Las Vegas, Nevada, 89102
UCLA-David Geffen School of Medicine
Los Angeles, California, 90095
Allergy, Asthma and Pulmonary Clinical Research
Madison, Wisconsin, 53792
Winthrop University Hospital
Mineola, New York, 11501
Mount Sinai School of Medicine
New York, New York, 10029
UMDNJ Asthma and Allergy Research Center
Newark, New Jersey, 07103
Orlando Regional Healthcare
Orlando, Florida, 32806
Virginia Adult and Pediatric Allergy and Asthma
Richmond, Virginia, 23229
Allergy and Asthma Research Center
San Antonio, Texas, 78229
University of California, San Diego
San Diego, California, 92093-0732
Allergy and Immunology Associates
Scottsdale, Arizona, 85251
Marycliff Allergy Specialists
Spokane, Washington, 99204
St. Louis University School of Medicine
St Louis, Missouri, 63110
Puget Sound Allergy, Asthma and Immunology
Tacoma, Washington, 98405
Montefiore Medical Center
The Bronx, New York, 10461
Grand Traverse Allergy
Traverse City, Michigan, 49684
Allergy Clinic of Tulsa
Tulsa, Oklahoma, 74133
Allergy and Asthma Clinical Research, Inc
Walnut Creek, California, 94598
Institute for Asthma and Allergy
Wheaton, Maryland, 20902
University of Massachusetts Medical School
Worcester, Massachusetts, 01655
About this study
Official title: LEVP2005-1/Part A: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) for the Treatment of HAE in Acute Attacks
The study objective was to determine the safety and efficacy of C1INH-nf for the treatment of acute HAE attacks.
Read the detailed description
Randomized subjects treated for a qualifying attack were eligible to receive rescue dosing with 1,000 U of C1INH-nf if they did not achieve beginning of substantial relief of the defining symptom within 4 hours after initial treatment with blinded study drug, or if at any time the attack progressed to include airway compromise. A second 1,000 U rescue dose was permitted 60 minutes after the initial rescue dose, if necessary.
The study design also allowed for administration of open-label C1INH-nf for laryngeal angioedema attacks, which were non-randomizable events due to the presence of or potential for airway compromise (immediate 1,000 U dose of C1INH-nf, repeated after 60 minutes, if necessary). In addition, subjects were eligible to receive open-label C1INH-nf (1,000 U single dose) prior to emergency surgical (non-cosmetic) procedures.
A total of 83 subjects were enrolled in the study. Seventy-one (71) subjects experienced qualifying attacks and were randomized to blinded study drug (36 C1INH-nf, 35 placebo); only the 71 randomized subjects were analyzed for efficacy. An additional 12 subjects were never randomized but received open-label C1INH-nf for treatment of laryngeal angioedema and/or prior to emergency surgical procedures. Of the 35 subjects randomized to placebo, 23 also received C1INH-nf (eg, rescue, open-label). In total, 83 subjects received at least 1 dose of study drug and were analyzed for safety; 71 subjects were exposed to C1INH-nf (59 randomized, 12 open-label only) and 12 subjects were exposed only to placebo.
- Conditions
- Hereditary Angioedema
- Being tested
- C1 esterase inhibitor [human] (C1INH-nf), Placebo (saline)
- Keywords
- Hereditary angioedema, HAE, C1 esterase inhibitor (human), C1INH-nf
- 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 inhibitor [human] (C1INH-nf)Biological
Placebo (saline)Drug
| Study group | Role | What they receive |
|---|---|---|
| C1INH-nf | Experimental | 1,000 Units (U) of C1INH-nf administered intravenously (IV). If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered. Receives: Biological: C1 esterase inhibitor [human] (C1INH-nf) |
| Placebo | Placebo comparator | Matching placebo (saline) administered IV. If there was no response to treatment 60 minutes after the first dose, a second placebo (saline) dose could be administered. Receives: Drug: Placebo (saline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Beginning of Substantial Relief of the Defining Symptom
Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug or until substantial relief of the defining symptom was achieved. Substantial relief was defined as 3 consecutive assessments of improvement of the defining symptom. Beginning of substantial relief was considered the first of the 3 consecutive assessments.
Measured: Within 4 hours after initial treatment
Secondary outcomes (5)
Number of Subjects With Beginning of Substantial Relief of the Defining Symptom
Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug or until substantial relief of the defining symptom was achieved. Substantial relief was defined as 3 consecutive assessments of improvement of the defining symptom. Beginning of substantial relief was considered the first of the 3 consecutive assessments.
Measured: Within 4 hours after initial treatment
Time to Complete Resolution of the HAE Attack
Randomized subjects were contacted 72-96 hours (3-4 days) after discharge from the study site to determine when complete resolution of the HAE attack occurred.
Measured: 72 hours
Antigenic C1 Inhibitor (C1INH) Serum Levels
Change in antigenic C1INH serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug.
Measured: Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion
Functional C1INH Serum Levels
Percent change in functional C1INH serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (ie, functional C1INH/total detectable C1INH).
Measured: Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion
Complement C4 Serum Levels
Change in complement C4 serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug.
Measured: Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2006 (estimated)
- Study start14 Mar 2005
- Primary completion13 Apr 2007
- Study completion13 Apr 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 (3)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00289211
- Sponsor's protocol ID
- LEVP2005-1/Part A
- Status last verified
- Jun 2021
- First submitted
- 7 Feb 2006
- Last updated
- 11 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Lumry W, Manning ME, Hurewitz DS, Davis-Lorton M, Fitts D, Kalfus IN, Uknis ME. Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. J Pediatr. 2013 May;162(5):1017-22.e1-2. doi: 10.1016/j.jpeds.2012.11.030. Epub 2013 Jan 11.
PubMed 23312695Grant JA, White MV, Li HH, Fitts D, Kalfus IN, Uknis ME, Lumry WR. Preprocedural administration of nanofiltered C1 esterase inhibitor to prevent hereditary angioedema attacks. Allergy Asthma Proc. 2012 Jul-Aug;33(4):348-53. doi: 10.2500/aap.2012.33.3585.
PubMed 22856635Zuraw BL, Busse PJ, White M, Jacobs J, Lumry W, Baker J, Craig T, Grant JA, Hurewitz D, Bielory L, Cartwright WE, Koleilat M, Ryan W, Schaefer O, Manning M, Patel P, Bernstein JA, Friedman RA, Wilkinson R, Tanner D, Kohler G, Gunther G, Levy R, McClellan J, Redhead J, Guss D, Heyman E, Blumenstein BA, Kalfus I, Frank MM. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):513-22. doi: 10.1056/NEJMoa0805538.
PubMed 20818886
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LEVP2005-1/Part A: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) for the Treatment of HAE in Acute Attacks
- ClinicalTrials.gov ID
- NCT00289211
- Acronym / sponsor ID
- LEVP2005-1/Part A
- Conditions
- Hereditary Angioedema
- Keywords
- Hereditary angioedema, HAE, C1 esterase inhibitor (human), C1INH-nf
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 14 Mar 2005 (actual)
- Primary completion
- 13 Apr 2007 (actual)
- Study completion
- 13 Apr 2007 (actual)
- First posted
- 9 Feb 2006 (estimated)
- Results
- Posted 2 Jun 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study objective was to determine the safety and efficacy of C1INH-nf for the treatment of acute HAE attacks.
Detailed description
Randomized subjects treated for a qualifying attack were eligible to receive rescue dosing with 1,000 U of C1INH-nf if they did not achieve beginning of substantial relief of the defining symptom within 4 hours after initial treatment with blinded study drug, or if at any time the attack progressed to include airway compromise. A second 1,000 U rescue dose was permitted 60 minutes after the initial rescue dose, if necessary.
The study design also allowed for administration of open-label C1INH-nf for laryngeal angioedema attacks, which were non-randomizable events due to the presence of or potential for airway compromise (immediate 1,000 U dose of C1INH-nf, repeated after 60 minutes, if necessary). In addition, subjects were eligible to receive open-label C1INH-nf (1,000 U single dose) prior to emergency surgical (non-cosmetic) procedures.
A total of 83 subjects were enrolled in the study. Seventy-one (71) subjects experienced qualifying attacks and were randomized to blinded study drug (36 C1INH-nf, 35 placebo); only the 71 randomized subjects were analyzed for efficacy. An additional 12 subjects were never randomized but received open-label C1INH-nf for treatment of laryngeal angioedema and/or prior to emergency surgical procedures. Of the 35 subjects randomized to placebo, 23 also received C1INH-nf (eg, rescue, open-label). In total, 83 subjects received at least 1 dose of study drug and were analyzed for safety; 71 subjects were exposed to C1INH-nf (59 randomized, 12 open-label only) and 12 subjects were exposed only to placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| C1INH-nf | Experimental | Biological: C1 esterase inhibitor [human] (C1INH-nf)1,000 Units (U) of C1INH-nf administered intravenously (IV). If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered. |
| Placebo | Placebo comparator | Drug: Placebo (saline)Matching placebo (saline) administered IV. If there was no response to treatment 60 minutes after the first dose, a second placebo (saline) dose could be administered. |
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 HAE
- Normal C1q level
Key exclusion criteria (9 listed)
- Low C1q level
- B-cell malignancy
- Presence of anti-C1INH autoantibody
- History of allergic reaction to C1INH or other blood products
- Narcotic addiction
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 [human] (C1INH-nf) | Biological | C1INH-nf |
| Placebo (saline) | Drug | Placebo |
Primary outcome
Time to Beginning of Substantial Relief of the Defining Symptom
Time frame: Within 4 hours after initial treatment
Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug or until substantial relief of the defining symptom was achieved. Substantial relief was defined as 3 consecutive assessments of improvement of the defining symptom. Beginning of substantial relief was considered the first of the 3 consecutive assessments.
5 secondary outcomes
Number of Subjects With Beginning of Substantial Relief of the Defining Symptom
Time frame: Within 4 hours after initial treatment
Time to Complete Resolution of the HAE Attack
Time frame: 72 hours
Antigenic C1 Inhibitor (C1INH) Serum Levels
Time frame: Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion
Functional C1INH Serum Levels
Time frame: Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion
Complement C4 Serum Levels
Time frame: Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23312695Lumry W, Manning ME, Hurewitz DS, Davis-Lorton M, Fitts D, Kalfus IN, Uknis ME. Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. J Pediatr. 2013 May;162(5):1017-22.e1-2. doi: 10.1016/j.jpeds.2012.11.030. Epub 2013 Jan 11.
- Derived from this study: PubMed 22856635Grant JA, White MV, Li HH, Fitts D, Kalfus IN, Uknis ME, Lumry WR. Preprocedural administration of nanofiltered C1 esterase inhibitor to prevent hereditary angioedema attacks. Allergy Asthma Proc. 2012 Jul-Aug;33(4):348-53. doi: 10.2500/aap.2012.33.3585.
- Derived from this study: PubMed 20818886Zuraw BL, Busse PJ, White M, Jacobs J, Lumry W, Baker J, Craig T, Grant JA, Hurewitz D, Bielory L, Cartwright WE, Koleilat M, Ryan W, Schaefer O, Manning M, Patel P, Bernstein JA, Friedman RA, Wilkinson R, Tanner D, Kohler G, Gunther G, Levy R, McClellan J, Redhead J, Guss D, Heyman E, Blumenstein BA, Kalfus I, Frank MM. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):513-22. doi: 10.1056/NEJMoa0805538.
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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.
Study Director study director
Takeda
37 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing C1 esterase inhibitor [human] (C1INH-nf) in people with Hereditary Angioedema, run by Shire at 37 sites in United States.
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 9 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 11 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United States. 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 phase mean?
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 2 Jun 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 Beginning of Substantial Relief of the Defining Symptom (time frame: Within 4 hours after initial 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 NCT00289211, which also lists 3 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 11 Jun 2021.