Hereditary AngioedemaPhase 3CHANGE 2NCT00438815
Open-Label 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 30 sites in United States.
Trial summary
The study objective was to evaluate the safety and efficacy of repeat use of C1INH-nf for the treatment of acute HAE attacks. Read more about this study
- Who is it for?
- Ages 1 year 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?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- 30 sitesUnited States
- Study dates
- 21 Sep 2006to 31 Mar 2009
- 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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- This study was open to all subjects who:
- Completed participation in LEVP2005-1/A (NCT00289211) and were not participating in LEVP2005-1/B (NCT01005888), any time after the 3-day telephone follow-up
- Completed participation in LEVP2005-1/B any time after the final prophylactic therapy in Part B
- Were enrolled but not randomized in LEVP2005-1/A after Part A was closed
- Were excluded from LEVP2005-1 for any of the following reasons:
- Pregnancy or lactation
Show all 13Show fewer
- Age less than 6 years
- Narcotic addiction
- Presence of anti-C1INH autoantibodies
- Were not enrolled in LEVP2005-1 after enrollment in LEVP2005-1 was closed, under the following circumstances:
- Had a diagnosis of HAE: evidence of a low C4 level plus either a low C1INH antigenic level or a low C1INH functional level, or
- Had a known HAE-causing C1INH mutation, or
- Had a diagnosis of HAE based on a strong family history of HAE as determined by the principal investigator
Who cannot join
- History of allergic reaction to C1INH or other blood products
- Participated in any other investigational drug study within the past 30 days
- Received blood or a blood product in the past 60 days other than C1INH-nf
Trial locations and contacts
30 sites in 1 country.
30 sites in 1 country
United States30 sites
Family Allergy and Asthma Center
Atlanta, Georgia, 30342
MeritCare Clinical Research
Bemidji, Minnesota, 56601
Allergy and Asthma Clinic of Northwest Arkansas
Bentonville, Arkansas, 72712
Allergy & Asthma Centre of Dayton
Centerville, Ohio, 45458
AARA Research Center
Dallas, Texas, 75231
Welborn Clinic Allergy and Immunology
Evansville, Indiana, 47713
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
Baylor College of Medicine
Houston, Texas, 77030
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
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
Cornerstone Healthcare
Parkersburg, West Virginia, 26101
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
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: LEVP2006-1 CHANGE 2 Trial (C1-Inhibitor in Hereditary Angioedema Nanofiltration Generation Evaluating Efficacy): Open-Label Safety/Efficacy Repeat Exposure Study of C1INH-nf (Human) in the Treatment of Acute HAE Attacks
The study objective was to evaluate the safety and efficacy of repeat use of C1INH-nf for the treatment of acute HAE attacks.
Read the detailed description
A total of 113 subjects were enrolled in the study. One-hundred-one (101) subjects received C1INH-nf for the treatment of 1 or more HAE attacks and were analyzed for efficacy. The study design also allowed for short-term prophylaxis with C1INH-nf prior to emergency or non-cosmetic surgical or dental procedures, and an additional 12 subjects received C1INH-nf only for this purpose. All 113 subjects were exposed to C1INH-nf and analyzed for safety.
- Conditions
- Hereditary Angioedema
- Being tested
- C1 esterase inhibitor [human] (C1INH-nf)
- Keywords
- Hereditary angioedema, C1 esterase inhibitor (human)
- 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
| Study group | Role | What they receive |
|---|---|---|
| Open-label C1INH-nf | Experimental | 1,000 Units (U) of C1INH-nf administered intravenously. 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf
Measured: Duration of the study (2.5 years)
Percent of HAE Attacks With Substantial Relief of the Defining Symptom
Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose or until substantial relief of the defining symptom was achieved. The conservative analysis defined substantial relief as 3 consecutive assessments of improvement of the defining symptom; any attack that did not have 3 consecutive documented reports of improvement was considered a treatment failure. In the less conservative analysis, attacks also were considered to have responded if clinical improvement of the defining symptom occurred but data were incomplete due to cessation of symptom assessments.
Measured: Within 4 hours after initial treatment
Secondary outcomes (5)
Time to Beginning of Substantial Relief of the Defining Symptom
Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose 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 Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments
For attack number 1, the number of censored observations precluded estimation of the 95% confidence interval (CI) upper bound for median time to event (subjects who did not experience beginning of substantial relief of the defining symptom within 4 hours after initial treatment were included in the analysis as censored observations). Entry of 4.0 hours indicates that data were not estimable (NE); as non-numeric data are not supported by the 95% CI field, entry of the actual result (ie, NE or >4.0) was not possible.
Measured: Within 4 hours after initial treatment
Antigenic C1 Inhibitor (C1INH) Serum Levels
Change in antigenic C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug.
Measured: Pre-infusion to 1 hour post-infusion
Functional C1INH Serum Levels
Percent change in functional C1INH serum levels from pre-infusion to 1 hour after the initial dose of 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 hour post-infusion
Complement C4 Serum Levels
Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.
Measured: Pre-infusion to 1 hour post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2007 (estimated)
- Study start21 Sep 2006
- Primary completion31 Mar 2009
- Study completion31 Mar 2009
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 (5)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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 113 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
- NCT00438815
- Sponsor's protocol ID
- LEVP2006-1
- Acronym
- CHANGE 2
- Status last verified
- May 2021
- First submitted
- 21 Feb 2007
- Last updated
- 8 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Baker JW, Craig TJ, Riedl MA, Banerji A, Fitts D, Kalfus IN, Uknis ME. Nanofiltered C1 esterase inhibitor (human) for hereditary angioedema attacks in pregnant women. Allergy Asthma Proc. 2013 Mar-Apr;34(2):162-9. doi: 10.2500/aap.2013.34.3645.
PubMed 23484892Lumry 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 22856635Riedl MA, Hurewitz DS, Levy R, Busse PJ, Fitts D, Kalfus I. Nanofiltered C1 esterase inhibitor (human) for the treatment of acute attacks of hereditary angioedema: an open-label trial. Ann Allergy Asthma Immunol. 2012 Jan;108(1):49-53. doi: 10.1016/j.anai.2011.10.017. Epub 2011 Nov 21.
PubMed 22192966Zuraw 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 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LEVP2006-1 CHANGE 2 Trial (C1-Inhibitor in Hereditary Angioedema Nanofiltration Generation Evaluating Efficacy): Open-Label Safety/Efficacy Repeat Exposure Study of C1INH-nf (Human) in the Treatment of Acute HAE Attacks
- ClinicalTrials.gov ID
- NCT00438815
- Acronym / sponsor ID
- CHANGE 2 / LEVP2006-1
- Conditions
- Hereditary Angioedema
- Keywords
- Hereditary angioedema, C1 esterase inhibitor (human)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 21 Sep 2006 (actual)
- Primary completion
- 31 Mar 2009 (actual)
- Study completion
- 31 Mar 2009 (actual)
- First posted
- 22 Feb 2007 (estimated)
- Results
- Posted 9 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 evaluate the safety and efficacy of repeat use of C1INH-nf for the treatment of acute HAE attacks.
Detailed description
A total of 113 subjects were enrolled in the study. One-hundred-one (101) subjects received C1INH-nf for the treatment of 1 or more HAE attacks and were analyzed for efficacy. The study design also allowed for short-term prophylaxis with C1INH-nf prior to emergency or non-cosmetic surgical or dental procedures, and an additional 12 subjects received C1INH-nf only for this purpose. All 113 subjects were exposed to C1INH-nf and analyzed for safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open-label C1INH-nf | Experimental | Biological: C1 esterase inhibitor [human] (C1INH-nf)1,000 Units (U) of C1INH-nf administered intravenously. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Completed participation in LEVP2005-1/A (NCT00289211) and were not participating in LEVP2005-1/B (NCT01005888), any time after the 3-day telephone follow-up
- Completed participation in LEVP2005-1/B any time after the final prophylactic therapy in Part B
- Were enrolled but not randomized in LEVP2005-1/A after Part A was closed
- Were excluded from LEVP2005-1 for any of the following reasons:
- Were not enrolled in LEVP2005-1 after enrollment in LEVP2005-1 was closed, under the following circumstances:
Key exclusion criteria (3 listed)
- History of allergic reaction to C1INH or other blood products
- Participated in any other investigational drug study within the past 30 days
- Received blood or a blood product in the past 60 days other than C1INH-nf
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 | Open-label C1INH-nf |
Primary outcome
Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf
Time frame: Duration of the study (2.5 years)
Percent of HAE Attacks With Substantial Relief of the Defining Symptom
Time frame: Within 4 hours after initial treatment
Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose or until substantial relief of the defining symptom was achieved. The conservative analysis defined substantial relief as 3 consecutive assessments of improvement of the defining symptom; any attack that did not have 3 consecutive documented reports of improvement was considered a treatment failure. In the less conservative analysis, attacks also were considered to have responded if clinical improvement of the defining symptom occurred but data were incomplete due to cessation of symptom assessments.
5 secondary outcomes
Time to Beginning of Substantial Relief of the Defining Symptom
Time frame: Within 4 hours after initial treatment
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments
Time frame: Within 4 hours after initial treatment
Antigenic C1 Inhibitor (C1INH) Serum Levels
Time frame: Pre-infusion to 1 hour post-infusion
Functional C1INH Serum Levels
Time frame: Pre-infusion to 1 hour post-infusion
Complement C4 Serum Levels
Time frame: Pre-infusion to 1 hour post-infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23484892Baker JW, Craig TJ, Riedl MA, Banerji A, Fitts D, Kalfus IN, Uknis ME. Nanofiltered C1 esterase inhibitor (human) for hereditary angioedema attacks in pregnant women. Allergy Asthma Proc. 2013 Mar-Apr;34(2):162-9. doi: 10.2500/aap.2013.34.3645.
- 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 22192966Riedl MA, Hurewitz DS, Levy R, Busse PJ, Fitts D, Kalfus I. Nanofiltered C1 esterase inhibitor (human) for the treatment of acute attacks of hereditary angioedema: an open-label trial. Ann Allergy Asthma Immunol. 2012 Jan;108(1):49-53. doi: 10.1016/j.anai.2011.10.017. Epub 2011 Nov 21.
- 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
30 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 30 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 13 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 8 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 30 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 9 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 Treated With C1INH-nf (time frame: Duration of the study (2.5 years)). The study lists 2 primary outcomes in all. 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 NCT00438815, which also lists 5 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 8 Jun 2021.