Clinical trial NCT00457015: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema (HAE)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2007-04-05
Enrollment: 96
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose
timeFrame: baseline, 4 hours post-dose
Secondary outcomes:
measure: Treatment Outcome Score at 4 Hours Post-Dose
timeFrame: 4 hours post-dose
measure: Patients With Significant Improvement in Overall Response
timeFrame: 4 hours post-dose
measure: Patients With a Successful Response at 4 Hours Post-dosing, Based on the Change From Baseline in the MSCS Score
timeFrame: baseline, 4 hours post-dosing
measure: Proportion of Patients Maintaining a Significant Improvement in Overall Response Through 24 Hours
timeFrame: 24 hours post-dosing
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Aaron J. Davis
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Little Rock
country: United States
facility: Little Rock Allergy & Asthma Clinic
state: Arkansas
city: Berkeley
country: United States
facility: Alta Bates Comprehensive Cancer Center
state: California
city: Crescent City
country: United States
facility: Pacific Coast Allergy
state: California
city: Granada Hills
country: United States
facility: Jacob Offenberger
state: California
city: Los Angeles
country: United States
facility: UCLA David Geffen School of Medicine, Department of Medicine
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates, P.C.
state: Colorado
city: Newark
country: United States
facility: Christiana Hospital
state: Delaware
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Miami
country: United States
facility: University of Miami, General Clinical Research Center
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: West Palm Beach
country: United States
facility: Roberson Allergy and Asthma
state: Florida
city: Atlanta
country: United States
facility: Family Allergy & Asthma Center, PC
state: Georgia
city: Columbus
country: United States
facility: Allergy Center of Brookstone
state: Georgia
city: Chicago
country: United States
facility: University Consultants in Allergy and Immunology
state: Illinois
city: Muncie
country: United States
facility: Muncie Allergy Center
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Allergy & Asthma
state: Kansas
city: Wheaton
country: United States
facility: Institute for Asthma and Allergy
state: Maryland
city: Chestnut Hill
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Clinton Township
country: United States
facility: Asthma and Allergy Institute of Michigan
state: Michigan
city: Ypsilanti
country: United States
facility: Respiratory Medicine Research Institute of Michigan, PLC
state: Michigan
city: Las Vegas
country: United States
facility: Nevada Access to Research and Education Society
state: Nevada
city: Reno
country: United States
facility: University of Nevada School of Medicine
state: Nevada
city: Newark
country: United States
facility: UMDNJ-New Jersey Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: Allergy Partners of Albuquerque
state: New Mexico
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: Asheville
country: United States
facility: Allergy Partners of Western North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Optimed Research, LLC
state: Ohio
city: Easton
country: United States
facility: Valley Clinical Research Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Asthma Allergy and Pulmonary Associates
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Childrens Hospital of Pittsburgh
state: Pennsylvania
city: Bristol
country: United States
facility: Highlands Allergy and Asthma Center, PC
state: Tennessee
city: Bryan
country: United States
facility: The Paull Allergy and Asthma Clinic, P.A.
state: Texas
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical School
state: Texas
city: Houston
country: United States
facility: Baylor Clinic, Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
city: Tacoma
country: United States
facility: Puget Sound Allergy, Asthma, & Immunology
state: Washington
city: Ottawa
country: Canada
facility: Allergy and Asthma Research Center
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
city: Amman
country: Jordan
facility: Jordan University Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
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.