Hereditary Angioedema (HAE)Phase 3NCT00457015
Efficacy Study of DX-88 (Ecallantide) to Treat Acute Attacks of Hereditary Angioedema (HAE)
A Phase 3 study testing ecallantide and Phosphate Buffer Saline (PBS), pH 7.0 in people with Hereditary Angioedema (HAE), run by Shire at 45 sites in 3 countries.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of DX-88 (ecallantide) versus placebo in the treatment of moderate to severe acute attacks of hereditary angioedema. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Hereditary Angioedema (HAE)
- What is being tested?
- ecallantide and Phosphate Buffer Saline (PBS), pH 7.0
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 45 sitesin 3 countries
- Study dates
- 1 Apr 2007to 1 Jun 2008
- 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 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 10 years of age or older
- Executed informed consent
- Documented diagnosis of HAE (Type I or II)
- Presentation at the site within 8 hours of patient recognition of an moderate to severe HAE acute attack
Who cannot join
- Receipt of an investigational drug or device, within 30 days prior to study treatment
- Receipt of non-investigational C1-INH within 7 days of treatment
- Receipt of DX-88 (ecallantide) within 3 days prior to study treatment
- Diagnosis of acquired angioedema (AAE), estrogen-dependent angioedema or drug-induced angioedema (including angiotensin-converting enzyme inhibitor induced angioedema)
- Pregnancy or breastfeeding
Trial locations and contacts
45 sites in 3 countries.
45 sites in 3 countries
United States42 sites
Allergy Partners of Albuquerque
Albuquerque, New Mexico, 87109
Allergy Partners of Western North Carolina
Asheville, North Carolina, 28801
Family Allergy & Asthma Center, PC
Atlanta, Georgia, 30342
Alta Bates Comprehensive Cancer Center
Berkeley, California, 94704
Highlands Allergy and Asthma Center, PC
Bristol, Tennessee, 37620
The Paull Allergy and Asthma Clinic, P.A.
Bryan, Texas, 77802
Brigham and Women's Hospital
Chestnut Hill, Massachusetts, 02467
University Consultants in Allergy and Immunology
Chicago, Illinois, 60612
University of Cincinnati
Cincinnati, Ohio, 45267
Asthma and Allergy Institute of Michigan
Clinton Township, Michigan, 48038
Asthma and Allergy Associates, P.C.
Colorado Springs, Colorado, 80907
Allergy Center of Brookstone
Columbus, Georgia, 31904
Optimed Research, LLC
Columbus, Ohio, 43235
Pacific Coast Allergy
Crescent City, California, 95531
AARA Research Center
Dallas, Texas, 75231
Valley Clinical Research Center
Easton, Pennsylvania, 18045
University of Texas Medical School
Galveston, Texas, 77555-1083
Jacob Offenberger
Granada Hills, California, 91344
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Baylor Clinic, Baylor College of Medicine
Houston, Texas, 77030
Nevada Access to Research and Education Society
Las Vegas, Nevada, 89102
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Little Rock Allergy & Asthma Clinic
Little Rock, Arkansas, 72205
UCLA David Geffen School of Medicine, Department of Medicine
Los Angeles, California, 90095-1680
University of Miami, General Clinical Research Center
Miami, Florida, 33136
Winthrop University Hospital
Mineola, New York, 11501
Muncie Allergy Center
Muncie, Indiana, 47304
Christiana Hospital
Newark, Delaware, 19718
UMDNJ-New Jersey Medical School
Newark, New Jersey, 07103
Clinical Research Associates of Tidewater
Norfolk, Virginia, 23507
Kansas City Allergy & Asthma
Overland Park, Kansas, 66210
Asthma Allergy and Pulmonary Associates
Philadelphia, Pennsylvania, 19107
Childrens Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
University of Nevada School of Medicine
Reno, Nevada, 89503
University of Utah
Salt Lake City, Utah, 84132-2409
Aaron J. Davis
Scottsdale, Arizona, 85251
Puget Sound Allergy, Asthma, & Immunology
Tacoma, Washington, 98405
University of South Florida
Tampa, Florida, 33613
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Roberson Allergy and Asthma
West Palm Beach, Florida, 33401
Institute for Asthma and Allergy
Wheaton, Maryland, 20902
Respiratory Medicine Research Institute of Michigan, PLC
Ypsilanti, Michigan, 48197
Canada2 sites
Allergy and Asthma Research Center
Ottawa, Ontario, K1Y 4G2
University of Toronto
Toronto, Ontario, M4V 1R2
About this study
Official title: EDEMA4: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of DX-88 (Ecallantide) for the Treatment of Acute Attacks of Hereditary Angioedema
The purpose of this study is to evaluate the efficacy and safety of DX-88 (ecallantide) versus placebo in the treatment of moderate to severe acute attacks of hereditary angioedema.
Read the detailed description
This is a randomized placebo-controlled trial.
The study is designed to assess the efficacy and safety of 30 mg subcutaneous ecallantide versus placebo in the treatment of moderate to severe acute attacks of hereditary angioedema. This study is conducted under Special Protocol Assessment with the FDA and is designed to provide pivotal efficacy data on ecallantide. These data are intended to support the marketing authorization of ecallantide in the treatment of acute attacks of hereditary angioedema. Efficacy and safety of ecallantide will be evaluated in this study.
- Conditions
- Hereditary Angioedema (HAE)
- Being tested
- ecallantide, Phosphate Buffer Saline (PBS), pH 7.0
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ecallantideDrug
Also called DX-88
dose of 30 mg (10 mg/ml) given as 3 subcutaneous injections.
Phosphate Buffer Saline (PBS), pH 7.0Drug
given as three 1mL subcutaneous injections.
| Study group | Role | What they receive |
|---|---|---|
| DX-88 (ecallantide) | Experimental | DX-88 (ecallantide) 30 mg given as three 10 mg/mL subcutaneous injections. Receives: Drug: ecallantide |
| Placebo | Placebo comparator | Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections. Receives: Drug: Phosphate Buffer Saline (PBS), pH 7.0 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose
The Mean Symptom Complex Severity (MSCS) score is a validated, comprehensive point-in-time measure of symptom severity. At baseline and 4 hours, patients rated the severity on a categorical scale (0 = normal, 1 = mild, 2 = moderate, 3 = severe) for symptoms at each affected anatomical location. Ratings were averaged to obtain the MSCS score. A decrease in MSCS score reflected an improvement in symptoms; clinically meaningful improvement was indicated by a reduction in the score of 0.30 or more.
Measured: baseline, 4 hours post-dose
Secondary outcomes (4)
Treatment Outcome Score at 4 Hours Post-Dose
Treatment Outcome Score (TOS) is a validated, comprehensive measure of symptom response to treatment. At 4 hours , patient assessment of response characterized by their change from baseline in symptom severity and collected by anatomic site of attack involvement, was recorded on a categorical scale (significant improvement [100; best value]to significant worsening [-100; worst value]). Clinically meaningful improvement was indicated by a TOS of 30 or higher.
Measured: 4 hours post-dose
Patients With Significant Improvement in Overall Response
Patients were to be asked to perform an overall response assessment at intervals during the first 4 hours post-dose. Assessments were to be made relative to baseline (ie, immediately before initial dosing) using a 5-category scale. Categories were: significant improvement = "a lot better or resolved"; improvement = "a little better"; same = response unchanged; worsening = "a little worse"; significant worsening = "a lot worse". Significant improvement is the first time that a patient responded to the overall response assessment as "a lot better or resolved."
Measured: 4 hours post-dose
Patients With a Successful Response at 4 Hours Post-dosing, Based on the Change From Baseline in the MSCS Score
A successful response was defined as improvement in existing laryngeal symptom complex,stabilization of an existing peripheral symptom complex, or a change from baseline in the MSCS score at 4 hours of at least -1.0.
Measured: baseline, 4 hours post-dosing
Proportion of Patients Maintaining a Significant Improvement in Overall Response Through 24 Hours
Maintenance of significant improvement was defined as achieving and maintaining a significant improvement in overall response through 24 hours after dosing. Patient response categories were: significant improvement = "a lot better or resolved"; improvement = "a little better"; same = response unchanged; worsening = "a little worse"; significant worsening = "a lot worse".
Measured: 24 hours post-dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2007 (estimated)
- Study start1 Apr 2007
- Primary completion1 Jun 2008
- Study completion1 Jun 2008
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 (6)Papers the sponsor has linked to this study.
- Other trials for Hereditary Angioedema (HAE)Studies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 96 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
- NCT00457015
- Sponsor's protocol ID
- EDEMA4 (DX-88/20)
- Status last verified
- May 2021
- First submitted
- 4 Apr 2007
- Last updated
- 8 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Rubinstein E, Stolz LE, Sheffer AL, Stevens C, Bousvaros A. Abdominal attacks and treatment in hereditary angioedema with C1-inhibitor deficiency. BMC Gastroenterol. 2014 Apr 9;14:71. doi: 10.1186/1471-230X-14-71.
PubMed 24712435MacGinnitie AJ, Davis-Lorton M, Stolz LE, Tachdjian R. Use of ecallantide in pediatric hereditary angioedema. Pediatrics. 2013 Aug;132(2):e490-7. doi: 10.1542/peds.2013-0646. Epub 2013 Jul 22.
PubMed 23878046Sheffer AL, MacGinnitie AJ, Campion M, Stolz LE, Pullman WE. Outcomes after ecallantide treatment of laryngeal hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2013 Mar;110(3):184-188.e2. doi: 10.1016/j.anai.2012.12.007. Epub 2013 Jan 5.
PubMed 23548529Li HH, Campion M, Craig TJ, Soteres DF, Riedl M, Lumry WR, MacGinnitie AJ, Shea EP, Bernstein JA. Analysis of hereditary angioedema attacks requiring a second dose of ecallantide. Ann Allergy Asthma Immunol. 2013 Mar;110(3):168-72. doi: 10.1016/j.anai.2012.12.004. Epub 2013 Jan 8.
PubMed 23548526Bernstein JA, Shea EP, Koester J, Iarrobino R, Pullman WE. Assessment of rebound and relapse following ecallantide treatment for acute attacks of hereditary angioedema. Allergy. 2012 Sep;67(9):1173-80. doi: 10.1111/j.1398-9995.2012.02864.x. Epub 2012 Jul 5.
PubMed 22765833Riedl M, Campion M, Horn PT, Pullman WE. Response time for ecallantide treatment of acute hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2010 Dec;105(6):430-436.e2. doi: 10.1016/j.anai.2010.09.005. Epub 2010 Oct 25.
PubMed 21130380
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
- EDEMA4: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of DX-88 (Ecallantide) for the Treatment of Acute Attacks of Hereditary Angioedema
- ClinicalTrials.gov ID
- NCT00457015
- Acronym / sponsor ID
- EDEMA4 (DX-88/20)
- Conditions
- Hereditary Angioedema (HAE)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 1 Apr 2007 (actual)
- Primary completion
- 1 Jun 2008 (actual)
- Study completion
- 1 Jun 2008 (actual)
- First posted
- 5 Apr 2007 (estimated)
- Results
- Posted 4 May 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of DX-88 (ecallantide) versus placebo in the treatment of moderate to severe acute attacks of hereditary angioedema.
Detailed description
This is a randomized placebo-controlled trial.
The study is designed to assess the efficacy and safety of 30 mg subcutaneous ecallantide versus placebo in the treatment of moderate to severe acute attacks of hereditary angioedema. This study is conducted under Special Protocol Assessment with the FDA and is designed to provide pivotal efficacy data on ecallantide. These data are intended to support the marketing authorization of ecallantide in the treatment of acute attacks of hereditary angioedema. Efficacy and safety of ecallantide will be evaluated in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DX-88 (ecallantide) | Experimental | Drug: ecallantideDX-88 (ecallantide) 30 mg given as three 10 mg/mL subcutaneous injections. |
| Placebo | Placebo comparator | Drug: Phosphate Buffer Saline (PBS), pH 7.0Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections. |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 10 years of age or older
- Executed informed consent
- Documented diagnosis of HAE (Type I or II)
- Presentation at the site within 8 hours of patient recognition of an moderate to severe HAE acute attack
Key exclusion criteria (5 listed)
- Receipt of an investigational drug or device, within 30 days prior to study treatment
- Receipt of non-investigational C1-INH within 7 days of treatment
- Receipt of DX-88 (ecallantide) within 3 days prior to study treatment
- Diagnosis of acquired angioedema (AAE), estrogen-dependent angioedema or drug-induced angioedema (including angiotensin-converting enzyme inhibitor induced angioedema)
- Pregnancy or breastfeeding
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 |
|---|---|---|
| ecallantideAlso: DX-88dose of 30 mg (10 mg/ml) given as 3 subcutaneous injections. | Drug | DX-88 (ecallantide) |
| Phosphate Buffer Saline (PBS), pH 7.0given as three 1mL subcutaneous injections. | Drug | Placebo |
Primary outcome
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose
Time frame: baseline, 4 hours post-dose
The Mean Symptom Complex Severity (MSCS) score is a validated, comprehensive point-in-time measure of symptom severity. At baseline and 4 hours, patients rated the severity on a categorical scale (0 = normal, 1 = mild, 2 = moderate, 3 = severe) for symptoms at each affected anatomical location. Ratings were averaged to obtain the MSCS score. A decrease in MSCS score reflected an improvement in symptoms; clinically meaningful improvement was indicated by a reduction in the score of 0.30 or more.
4 secondary outcomes
Treatment Outcome Score at 4 Hours Post-Dose
Time frame: 4 hours post-dose
Patients With Significant Improvement in Overall Response
Time frame: 4 hours post-dose
Patients With a Successful Response at 4 Hours Post-dosing, Based on the Change From Baseline in the MSCS Score
Time frame: baseline, 4 hours post-dosing
Proportion of Patients Maintaining a Significant Improvement in Overall Response Through 24 Hours
Time frame: 24 hours post-dosing
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 24712435Rubinstein E, Stolz LE, Sheffer AL, Stevens C, Bousvaros A. Abdominal attacks and treatment in hereditary angioedema with C1-inhibitor deficiency. BMC Gastroenterol. 2014 Apr 9;14:71. doi: 10.1186/1471-230X-14-71.
- Derived from this study: PubMed 23878046MacGinnitie AJ, Davis-Lorton M, Stolz LE, Tachdjian R. Use of ecallantide in pediatric hereditary angioedema. Pediatrics. 2013 Aug;132(2):e490-7. doi: 10.1542/peds.2013-0646. Epub 2013 Jul 22.
- Derived from this study: PubMed 23548529Sheffer AL, MacGinnitie AJ, Campion M, Stolz LE, Pullman WE. Outcomes after ecallantide treatment of laryngeal hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2013 Mar;110(3):184-188.e2. doi: 10.1016/j.anai.2012.12.007. Epub 2013 Jan 5.
- Derived from this study: PubMed 23548526Li HH, Campion M, Craig TJ, Soteres DF, Riedl M, Lumry WR, MacGinnitie AJ, Shea EP, Bernstein JA. Analysis of hereditary angioedema attacks requiring a second dose of ecallantide. Ann Allergy Asthma Immunol. 2013 Mar;110(3):168-72. doi: 10.1016/j.anai.2012.12.004. Epub 2013 Jan 8.
- Derived from this study: PubMed 22765833Bernstein JA, Shea EP, Koester J, Iarrobino R, Pullman WE. Assessment of rebound and relapse following ecallantide treatment for acute attacks of hereditary angioedema. Allergy. 2012 Sep;67(9):1173-80. doi: 10.1111/j.1398-9995.2012.02864.x. Epub 2012 Jul 5.
- Derived from this study: PubMed 21130380Riedl M, Campion M, Horn PT, Pullman WE. Response time for ecallantide treatment of acute hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2010 Dec;105(6):430-436.e2. doi: 10.1016/j.anai.2010.09.005. Epub 2010 Oct 25.
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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
45 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ecallantide and Phosphate Buffer Saline (PBS), pH 7.0 in people with Hereditary Angioedema (HAE), run by Shire at 45 sites in 3 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 5 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 45 sites in United States, Canada, Jordan. 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 4 May 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?
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose (time frame: baseline, 4 hours post-dose). 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 NCT00457015, which also lists 6 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.