Hereditary AngioedemaPhase 3NCT01005888
C1 Esterase Inhibitor (C1INH-nf) for the Prevention 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 16 sites in United States.
Trial summary
The study objective was to determine the safety and efficacy of C1INH-nf for the prevention 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
- 26 participants
- Where
- 16 sitesUnited States
- Study dates
- 14 Mar 2005to 22 Aug 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
- Relatively frequent angioedema attacks (at least 2 per month on average)
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
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Nationwide Childrens Hospital Clinical Research
Columbus, Ohio, 43205
AARA Research Center
Dallas, Texas, 75231
Welborn Clinic Allergy and Immunology
Evansville, Indiana, 47713
Hawaii Pacific Health Research Institute
Honolulu, Hawaii, 96826
Lake Charles Memorial Hospital
Lake Charles, Louisiana, 70601
Allergy Asthma and Dermatology Research Center
Lake Oswego, Oregon, 97035
Libby Clinic
Libby, Montana, 59923
Mount Sinai School of Medicine
New York, New York, 10029
St. Joseph's Hospital/Cornerstone Healthcare
Parkersburg, West Virginia, 26101
University of California, San Diego
San Diego, California, 92093-0732
Allergy and Immunology Associates
Scottsdale, Arizona, 85251
Atlanta Allergy and Asthma Clinic
Suwanee, Georgia, 30024
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
Tyler County Hospital
Woodville, Texas, 75979
About this study
Official title: LEVP2005-1/Part B: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) as Prophylactic Treatment to Prevent HAE Attacks
The study objective was to determine the safety and efficacy of C1INH-nf for the prevention of acute HAE attacks.
Read the detailed description
Subjects were given diary cards and instructed to document all HAE attacks on a daily basis. Subjects evaluated their symptoms over the previous 24 hours, noting the severity and duration of swelling at each of 5 locations (abdominal, genitourinary, facial, respiratory [including laryngeal], and/or extremity).
The study design also allowed for administration of open-label C1INH-nf (1,000 U of C1INH-nf administered IV [repeated after 60 minutes, if necessary] for treatment of laryngeal angioedema or if deemed necessary by the investigator; 1,000 U of C1INH-nf administered IV [single dose] prior to emergency surgical procedures).
A total of 26 subjects were enrolled in the study. One subject received open-label C1INH-nf but withdrew prior to randomization. Another subject was randomized but withdrew prior to receiving study drug. Twenty-four (24) subjects were randomized and treated with blinded study drug. In total, 25 subjects received at least 1 dose of study drug and were analyzed for safety; all 25 subjects were exposed to C1INH-nf and 23 subjects were exposed 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 First, then Placebo | Experimental | 1,000 Units (U) of C1INH-nf administered intravenously (IV) every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by matching placebo (saline) administered IV every 3 to 4 days for 12 weeks. Receives: Biological: C1 esterase inhibitor [human] (C1INH-nf); Drug: Placebo (saline) |
| Placebo First, then C1INH-nf | Experimental | Matching placebo (saline) administered IV every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by 1,000 U of C1INH-nf administered IV every 3 to 4 days for 12 weeks. Receives: Biological: C1 esterase inhibitor [human] (C1INH-nf); Drug: Placebo (saline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period
An HAE attack was defined as the subject-reported indication of swelling at any location following a report of no swelling on the previous day. Analyses include observed attack counts and normalized attack counts (i.e., the number of attacks observed during each therapy period, normalized for the number of days the subject participated in that period).
Measured: 12 weeks
Secondary outcomes (6)
Number of Subject Withdrawals During Each Prophylactic Therapy Period
At the end of each therapy period, each subject was assigned a yes/no drop-out status. A drop-out was defined as a subject who did not have a Week 12 visit record.
Measured: 12 weeks
Average Severity of HAE Attacks During Each Prophylactic Therapy Period
All attacks in each therapy period were assigned a value of 1 (mild), 2 (moderate), or 3 (severe). Attack severity was considered the highest value assigned by the subject to any swelling location during the attack. Average severity was set to 0 if there was no attack in a period.
Measured: 12 weeks
Average Duration of HAE Attacks During Each Prophylactic Therapy Period
The duration of an attack was measured from the first report of swelling at any one of the five locations (abdominal, genitourinary, facial, respiratory [including laryngeal], or extremity) until the first subsequent report of "no swelling" at all five locations.
Measured: 12 weeks
Number of Open-label C1INH-nf Infusions Required During Each Prophylactic Therapy Period
The study design allowed for subjects to be treated with open-label C1INH-nf for laryngeal angioedema, if deemed necessary by the investigator, or prior to emergency surgical procedures.
Measured: 12 weeks
Antigenic C1 Inhibitor (C1INH) Serum Levels
Change in antigenic C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits.
Measured: Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12
Functional C1INH Serum Levels
Percent change in functional C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (i.e., functional C1INH/total detectable C1INH).
Measured: Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2009 (estimated)
- Study start14 Mar 2005
- Primary completion22 Aug 2007
- Study completion22 Aug 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.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 26 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
- NCT01005888
- Sponsor's protocol ID
- LEVP2005-1/Part B
- Status last verified
- May 2021
- First submitted
- 29 Oct 2009
- Last updated
- 11 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
PubMed 36326435Lumry WR, Miller DP, Newcomer S, Fitts D, Dayno J. Quality of life in patients with hereditary angioedema receiving therapy for routine prevention of attacks. Allergy Asthma Proc. 2014 Sep-Oct;35(5):371-6. doi: 10.2500/aap.2014.35.3783.
PubMed 25295804Lumry 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 23312695Zuraw 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 B: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) as Prophylactic Treatment to Prevent HAE Attacks
- ClinicalTrials.gov ID
- NCT01005888
- Acronym / sponsor ID
- LEVP2005-1/Part B
- Conditions
- Hereditary Angioedema
- Keywords
- Hereditary angioedema, HAE, C1 esterase inhibitor (human), C1INH-nf
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 14 Mar 2005 (actual)
- Primary completion
- 22 Aug 2007 (actual)
- Study completion
- 22 Aug 2007 (actual)
- First posted
- 2 Nov 2009 (estimated)
- Results
- Posted 3 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 prevention of acute HAE attacks.
Detailed description
Subjects were given diary cards and instructed to document all HAE attacks on a daily basis. Subjects evaluated their symptoms over the previous 24 hours, noting the severity and duration of swelling at each of 5 locations (abdominal, genitourinary, facial, respiratory [including laryngeal], and/or extremity).
The study design also allowed for administration of open-label C1INH-nf (1,000 U of C1INH-nf administered IV [repeated after 60 minutes, if necessary] for treatment of laryngeal angioedema or if deemed necessary by the investigator; 1,000 U of C1INH-nf administered IV [single dose] prior to emergency surgical procedures).
A total of 26 subjects were enrolled in the study. One subject received open-label C1INH-nf but withdrew prior to randomization. Another subject was randomized but withdrew prior to receiving study drug. Twenty-four (24) subjects were randomized and treated with blinded study drug. In total, 25 subjects received at least 1 dose of study drug and were analyzed for safety; all 25 subjects were exposed to C1INH-nf and 23 subjects were exposed to placebo.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| C1INH-nf First, then Placebo | Experimental | Biological: C1 esterase inhibitor [human] (C1INH-nf), Drug: Placebo (saline)1,000 Units (U) of C1INH-nf administered intravenously (IV) every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by matching placebo (saline) administered IV every 3 to 4 days for 12 weeks. |
| Placebo First, then C1INH-nf | Experimental | Biological: C1 esterase inhibitor [human] (C1INH-nf), Drug: Placebo (saline)Matching placebo (saline) administered IV every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by 1,000 U of C1INH-nf administered IV every 3 to 4 days for 12 weeks. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Documented HAE
- Normal C1q level
- Relatively frequent angioedema attacks (at least 2 per month on average)
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 First, then Placebo, Placebo First, then C1INH-nf |
| Placebo (saline) | Drug | C1INH-nf First, then Placebo, Placebo First, then C1INH-nf |
Primary outcome
Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period
Time frame: 12 weeks
An HAE attack was defined as the subject-reported indication of swelling at any location following a report of no swelling on the previous day. Analyses include observed attack counts and normalized attack counts (i.e., the number of attacks observed during each therapy period, normalized for the number of days the subject participated in that period).
6 secondary outcomes
Number of Subject Withdrawals During Each Prophylactic Therapy Period
Time frame: 12 weeks
Average Severity of HAE Attacks During Each Prophylactic Therapy Period
Time frame: 12 weeks
Average Duration of HAE Attacks During Each Prophylactic Therapy Period
Time frame: 12 weeks
Number of Open-label C1INH-nf Infusions Required During Each Prophylactic Therapy Period
Time frame: 12 weeks
Antigenic C1 Inhibitor (C1INH) Serum Levels
Time frame: Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12
Functional C1INH Serum Levels
Time frame: Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12
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 36326435Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
- Derived from this study: PubMed 25295804Lumry WR, Miller DP, Newcomer S, Fitts D, Dayno J. Quality of life in patients with hereditary angioedema receiving therapy for routine prevention of attacks. Allergy Asthma Proc. 2014 Sep-Oct;35(5):371-6. doi: 10.2500/aap.2014.35.3783.
- 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 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.
Related trials for Hereditary Angioedema
RecruitingPhase 3
Donidalorsen Treatment in Children With Hereditary Angioedema
Hereditary Angioedema (HAE)
RecruitingObservational study
A Study of Takhzyro in Teenagers and Adults With Hereditary Angioedema (HAE) in South Korea
Hereditary Angioedema (HAE)
Active, not recruitingPhase 3
HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE)
Hereditary Angioedema
RecruitingPhase 3
Study of IV Human Plasma-derived C1 Esterase Inhibitor Concentrate in Patients With Congenital C1-INH Deficiency for Treatment and Pre-procedure Preventing of Acute Hereditary Angioedema Attacks
Acute Hereditary Angio Edema
Active, not recruitingPhase 1/2
NTLA-2002 in Adults With Hereditary Angioedema (HAE)
Hereditary Angioedema
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
16 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 16 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 3 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 16 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. 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 3 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?
Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period (time frame: 12 weeks). 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 NCT01005888, 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 11 Jun 2021.