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Efficacy Study of DX-88 (Ecallantide) to Treat Acute Attacks of Hereditary Angioedema (HAE)

Primary Purpose

Hereditary Angioedema (HAE)

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ecallantide
Phosphate Buffer Saline (PBS), pH 7.0
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hereditary Angioedema (HAE)

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Aaron J. Davis
  • Arkansas Children's Hospital
  • Little Rock Allergy & Asthma Clinic
  • Alta Bates Comprehensive Cancer Center
  • Pacific Coast Allergy
  • Jacob Offenberger
  • UCLA David Geffen School of Medicine, Department of Medicine
  • Asthma and Allergy Associates, P.C.
  • Christiana Hospital
  • Georgetown University Hospital
  • University of Miami, General Clinical Research Center
  • University of South Florida
  • Roberson Allergy and Asthma
  • Family Allergy & Asthma Center, PC
  • Allergy Center of Brookstone
  • University Consultants in Allergy and Immunology
  • Muncie Allergy Center
  • Kansas City Allergy & Asthma
  • Institute for Asthma and Allergy
  • Brigham and Women's Hospital
  • Asthma and Allergy Institute of Michigan
  • Respiratory Medicine Research Institute of Michigan, PLC
  • Nevada Access to Research and Education Society
  • University of Nevada School of Medicine
  • UMDNJ-New Jersey Medical School
  • Allergy Partners of Albuquerque
  • Winthrop University Hospital
  • Allergy Partners of Western North Carolina
  • University of Cincinnati
  • Optimed Research, LLC
  • Valley Clinical Research Center
  • Penn State Milton S. Hershey Medical Center
  • Asthma Allergy and Pulmonary Associates
  • Childrens Hospital of Pittsburgh
  • Highlands Allergy and Asthma Center, PC
  • The Paull Allergy and Asthma Clinic, P.A.
  • AARA Research Center
  • University of Texas Medical School
  • Baylor Clinic, Baylor College of Medicine
  • University of Utah
  • Clinical Research Associates of Tidewater
  • Puget Sound Allergy, Asthma, & Immunology
  • Allergy and Asthma Research Center
  • University of Toronto
  • Jordan University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

DX-88 (ecallantide)

Placebo

Arm Description

DX-88 (ecallantide) 30 mg given as three 10 mg/mL subcutaneous injections.

Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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."
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.
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".

Full Information

First Posted
April 4, 2007
Last Updated
May 14, 2021
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT00457015
Brief Title
Efficacy Study of DX-88 (Ecallantide) to Treat Acute Attacks of Hereditary Angioedema (HAE)
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
April 1, 2007 (Actual)
Primary Completion Date
June 1, 2008 (Actual)
Study Completion Date
June 1, 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema (HAE)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
96 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DX-88 (ecallantide)
Arm Type
Experimental
Arm Description
DX-88 (ecallantide) 30 mg given as three 10 mg/mL subcutaneous injections.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
Intervention Type
Drug
Intervention Name(s)
ecallantide
Other Intervention Name(s)
DX-88
Intervention Description
dose of 30 mg (10 mg/ml) given as 3 subcutaneous injections.
Intervention Type
Drug
Intervention Name(s)
Phosphate Buffer Saline (PBS), pH 7.0
Intervention Description
given as three 1mL subcutaneous injections.
Primary Outcome Measure Information:
Title
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose
Description
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.
Time Frame
baseline, 4 hours post-dose
Secondary Outcome Measure Information:
Title
Treatment Outcome Score at 4 Hours Post-Dose
Description
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.
Time Frame
4 hours post-dose
Title
Patients With Significant Improvement in Overall Response
Description
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."
Time Frame
4 hours post-dose
Title
Patients With a Successful Response at 4 Hours Post-dosing, Based on the Change From Baseline in the MSCS Score
Description
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.
Time Frame
baseline, 4 hours post-dosing
Title
Proportion of Patients Maintaining a Significant Improvement in Overall Response Through 24 Hours
Description
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".
Time Frame
24 hours post-dosing

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Aaron J. Davis
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Little Rock Allergy & Asthma Clinic
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Alta Bates Comprehensive Cancer Center
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
Pacific Coast Allergy
City
Crescent City
State/Province
California
ZIP/Postal Code
95531
Country
United States
Facility Name
Jacob Offenberger
City
Granada Hills
State/Province
California
ZIP/Postal Code
91344
Country
United States
Facility Name
UCLA David Geffen School of Medicine, Department of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1680
Country
United States
Facility Name
Asthma and Allergy Associates, P.C.
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Christiana Hospital
City
Newark
State/Province
Delaware
ZIP/Postal Code
19718
Country
United States
Facility Name
Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of Miami, General Clinical Research Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Roberson Allergy and Asthma
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
Facility Name
Family Allergy & Asthma Center, PC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Allergy Center of Brookstone
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904
Country
United States
Facility Name
University Consultants in Allergy and Immunology
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Muncie Allergy Center
City
Muncie
State/Province
Indiana
ZIP/Postal Code
47304
Country
United States
Facility Name
Kansas City Allergy & Asthma
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66210
Country
United States
Facility Name
Institute for Asthma and Allergy
City
Wheaton
State/Province
Maryland
ZIP/Postal Code
20902
Country
United States
Facility Name
Brigham and Women's Hospital
City
Chestnut Hill
State/Province
Massachusetts
ZIP/Postal Code
02467
Country
United States
Facility Name
Asthma and Allergy Institute of Michigan
City
Clinton Township
State/Province
Michigan
ZIP/Postal Code
48038
Country
United States
Facility Name
Respiratory Medicine Research Institute of Michigan, PLC
City
Ypsilanti
State/Province
Michigan
ZIP/Postal Code
48197
Country
United States
Facility Name
Nevada Access to Research and Education Society
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89102
Country
United States
Facility Name
University of Nevada School of Medicine
City
Reno
State/Province
Nevada
ZIP/Postal Code
89503
Country
United States
Facility Name
UMDNJ-New Jersey Medical School
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
Allergy Partners of Albuquerque
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87109
Country
United States
Facility Name
Winthrop University Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Allergy Partners of Western North Carolina
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Optimed Research, LLC
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Facility Name
Valley Clinical Research Center
City
Easton
State/Province
Pennsylvania
ZIP/Postal Code
18045
Country
United States
Facility Name
Penn State Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Asthma Allergy and Pulmonary Associates
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Childrens Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Highlands Allergy and Asthma Center, PC
City
Bristol
State/Province
Tennessee
ZIP/Postal Code
37620
Country
United States
Facility Name
The Paull Allergy and Asthma Clinic, P.A.
City
Bryan
State/Province
Texas
ZIP/Postal Code
77802
Country
United States
Facility Name
AARA Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
University of Texas Medical School
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555-1083
Country
United States
Facility Name
Baylor Clinic, Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132-2409
Country
United States
Facility Name
Clinical Research Associates of Tidewater
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Puget Sound Allergy, Asthma, & Immunology
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Allergy and Asthma Research Center
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4G2
Country
Canada
Facility Name
University of Toronto
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4V 1R2
Country
Canada
Facility Name
Jordan University Hospital
City
Amman
ZIP/Postal Code
1194
Country
Jordan

12. IPD Sharing Statement

Citations:
PubMed Identifier
24712435
Citation
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.
Results Reference
derived
PubMed Identifier
23878046
Citation
MacGinnitie 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.
Results Reference
derived
PubMed Identifier
23548529
Citation
Sheffer 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.
Results Reference
derived
PubMed Identifier
23548526
Citation
Li 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.
Results Reference
derived
PubMed Identifier
22765833
Citation
Bernstein 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.
Results Reference
derived
PubMed Identifier
21130380
Citation
Riedl 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.
Results Reference
derived

Learn more about this trial

Efficacy Study of DX-88 (Ecallantide) to Treat Acute Attacks of Hereditary Angioedema (HAE)

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