Hereditary Angioedema (HAE)Phase 3NCT00262080
Efficacy and Safety Study of DX-88 to Treat Acute Attacks of Hereditary Angioedema (HAE)
A Phase 3 study testing ecallantide and Phosphate Buffer Saline (PBS), in people with Hereditary Angioedema (HAE), run by Shire at 1 site in United States.
Trial summary
The purpose of this study is to determine if a subcutaneous dose of DX-88 (ecallantide; an investigational product) is safe and relieves symptoms of HAE in patients suffering from moderate to severe acute attacks of HAE. 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),
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 91 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Dec 2005to 28 Feb 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 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 10 and older
- Documented diagnosis of HAE, Type I or II
- Executed informed consent
- Presentation for treatment within 8 hours of patient recognition of moderate to severe HAE attack
Who cannot join
- Receipt of investigational drug or device, other than DX-88, within 30 days of treatment
- Receipt of non-investigational C1-INH (C1 esterase inhibitor) within 7 days of treatment
- Diagnostic of acquired angioedema, estrogen-dependent angioedema or drug induced angioedema
- Pregnancy or breastfeeding
- Patients who have received DX-88 within 7 days of presentation for dosing in the Double-blind Phase
Trial locations and contacts
1 site in 1 country.
United States1 site
Institute for Asthma and Allergy
Wheaton, Maryland, 20902
About this study
Official title: A Double-blind, Placebo-controlled Study (72 Patients, Randomized 1:1) Followed by a Repeat-dosing Phase to Assess the Efficacy and Safety of DX-88 (Ecallantide; Recombinant Plasma Kallikrein Inhibitor) for the Treatment of Acute Attacks of Hereditary Angioedema
The purpose of this study is to determine if a subcutaneous dose of DX-88 (ecallantide; an investigational product) is safe and relieves symptoms of HAE in patients suffering from moderate to severe acute attacks of HAE.
- Conditions
- Hereditary Angioedema (HAE)
- Being tested
- ecallantide, Phosphate Buffer Saline (PBS),
- 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),Drug
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 | Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections. Receives: Drug: Phosphate Buffer Saline (PBS), |
What is being measured
The primary outcome is the main question the study is designed to answer.
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] to significant worsening [-100]). The response at each anatomic site was weighted by baseline severity and then the weighted scores across all involved sites were averaged to calculate the TOS. Clinically meaningful improvement was indicated by a TOS of 30 or higher.
Measured: 4 hours post-dose (DOUBLE-BLIND PART)
Secondary outcomes (2)
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose
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 (minimally important difference) was indicated by a reduction in the score of 0.30 or more.
Measured: baseline, 4 hours post-dose (DOUBLE-BLIND PART)
Time to Significant Improvement in Overall Response
The overall response assessment is a patient-reported assessment of global response to therapy. Patients are asked to perform an overall response assessment at regular intervals, relative to baseline. Patients were asked "overall how are you feeling" compared to how they felt before study drug. Answer options were "a lot worse", "a little worse", "same", "a little better" or "a lot better or resolved". Significant improvement was the first time that the patient responded to the assessment as "a little better or resolved".
Measured: 4 hours post-dose (DOUBLE-BLIND PART)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2005 (estimated)
- Study start31 Dec 2005
- Primary completion31 Dec 2005
- Study completion28 Feb 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 (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
- 91 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
- NCT00262080
- Sponsor's protocol ID
- EDEMA3 (DX-88/14)
- Status last verified
- Jun 2021
- First submitted
- 5 Dec 2005
- Last updated
- 11 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 23548529Bernstein 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 21130380Cicardi M, Levy RJ, McNeil DL, Li HH, Sheffer AL, Campion M, Horn PT, Pullman WE. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):523-31. doi: 10.1056/NEJMoa0905079.
PubMed 20818887
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
- A Double-blind, Placebo-controlled Study (72 Patients, Randomized 1:1) Followed by a Repeat-dosing Phase to Assess the Efficacy and Safety of DX-88 (Ecallantide; Recombinant Plasma Kallikrein Inhibitor) for the Treatment of Acute Attacks of Hereditary Angioedema
- ClinicalTrials.gov ID
- NCT00262080
- Acronym / sponsor ID
- EDEMA3 (DX-88/14)
- Conditions
- Hereditary Angioedema (HAE)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 31 Dec 2005 (actual)
- Primary completion
- 31 Dec 2005 (actual)
- Study completion
- 28 Feb 2007 (actual)
- First posted
- 6 Dec 2005 (estimated)
- Results
- Posted 11 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 determine if a subcutaneous dose of DX-88 (ecallantide; an investigational product) is safe and relieves symptoms of HAE in patients suffering from moderate to severe acute attacks of HAE.
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),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)
- Age 10 and older
- Documented diagnosis of HAE, Type I or II
- Executed informed consent
- Presentation for treatment within 8 hours of patient recognition of moderate to severe HAE attack
Key exclusion criteria (5 listed)
- Receipt of investigational drug or device, other than DX-88, within 30 days of treatment
- Receipt of non-investigational C1-INH (C1 esterase inhibitor) within 7 days of treatment
- Diagnostic of acquired angioedema, estrogen-dependent angioedema or drug induced angioedema
- Pregnancy or breastfeeding
- Patients who have received DX-88 within 7 days of presentation for dosing in the Double-blind Phase
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),given as three 1mL subcutaneous injections. | Drug | Placebo |
Primary outcome
Treatment Outcome Score at 4 Hours Post-Dose
Time frame: 4 hours post-dose (DOUBLE-BLIND PART)
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] to significant worsening [-100]). The response at each anatomic site was weighted by baseline severity and then the weighted scores across all involved sites were averaged to calculate the TOS. Clinically meaningful improvement was indicated by a TOS of 30 or higher.
2 secondary outcomes
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose
Time frame: baseline, 4 hours post-dose (DOUBLE-BLIND PART)
Time to Significant Improvement in Overall Response
Time frame: 4 hours post-dose (DOUBLE-BLIND PART)
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 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 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.
- Derived from this study: PubMed 20818887Cicardi M, Levy RJ, McNeil DL, Li HH, Sheffer AL, Campion M, Horn PT, Pullman WE. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):523-31. doi: 10.1056/NEJMoa0905079.
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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
1 site in 1 country: 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), in people with Hereditary Angioedema (HAE), run by Shire at 1 site 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 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 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 1 site 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 11 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?
Treatment Outcome Score at 4 Hours Post-Dose (time frame: 4 hours post-dose (DOUBLE-BLIND PART)). 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 NCT00262080, 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 11 Jun 2021.