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

Hereditary Angioedema (HAE) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00457015
• Other study ID #: EDEMA4 (DX-88/20)
• Status: Completed
• Phase: Phase 3
• Start date: April 1, 2007
• Est. completion date: June 1, 2008

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: June 1, 2008
• Est. primary completion date: June 1, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema (HAE)

Intervention

Drug:
• ecallantide
dose of 30 mg (10 mg/ml) given as 3 subcutaneous injections.
• Phosphate Buffer Saline (PBS), pH 7.0
given as three 1mL subcutaneous injections.

Locations

Country	Name	City	State
Canada	Allergy and Asthma Research Center	Ottawa	Ontario
Canada	University of Toronto	Toronto	Ontario
Jordan	Jordan University Hospital	Amman
United States	Allergy Partners of Albuquerque	Albuquerque	New Mexico
United States	Allergy Partners of Western North Carolina	Asheville	North Carolina
United States	Family Allergy & Asthma Center, PC	Atlanta	Georgia
United States	Alta Bates Comprehensive Cancer Center	Berkeley	California
United States	Highlands Allergy and Asthma Center, PC	Bristol	Tennessee
United States	The Paull Allergy and Asthma Clinic, P.A.	Bryan	Texas
United States	Brigham and Women's Hospital	Chestnut Hill	Massachusetts
United States	University Consultants in Allergy and Immunology	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Asthma and Allergy Institute of Michigan	Clinton Township	Michigan
United States	Asthma and Allergy Associates, P.C.	Colorado Springs	Colorado
United States	Allergy Center of Brookstone	Columbus	Georgia
United States	Optimed Research, LLC	Columbus	Ohio
United States	Pacific Coast Allergy	Crescent City	California
United States	AARA Research Center	Dallas	Texas
United States	Valley Clinical Research Center	Easton	Pennsylvania
United States	University of Texas Medical School	Galveston	Texas
United States	Jacob Offenberger	Granada Hills	California
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor Clinic, Baylor College of Medicine	Houston	Texas
United States	Nevada Access to Research and Education Society	Las Vegas	Nevada
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Little Rock Allergy & Asthma Clinic	Little Rock	Arkansas
United States	UCLA David Geffen School of Medicine, Department of Medicine	Los Angeles	California
United States	University of Miami, General Clinical Research Center	Miami	Florida
United States	Winthrop University Hospital	Mineola	New York
United States	Muncie Allergy Center	Muncie	Indiana
United States	Christiana Hospital	Newark	Delaware
United States	UMDNJ-New Jersey Medical School	Newark	New Jersey
United States	Clinical Research Associates of Tidewater	Norfolk	Virginia
United States	Kansas City Allergy & Asthma	Overland Park	Kansas
United States	Asthma Allergy and Pulmonary Associates	Philadelphia	Pennsylvania
United States	Childrens Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Nevada School of Medicine	Reno	Nevada
United States	University of Utah	Salt Lake City	Utah
United States	Aaron J. Davis	Scottsdale	Arizona
United States	Puget Sound Allergy, Asthma, & Immunology	Tacoma	Washington
United States	University of South Florida	Tampa	Florida
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Roberson Allergy and Asthma	West Palm Beach	Florida
United States	Institute for Asthma and Allergy	Wheaton	Maryland
United States	Respiratory Medicine Research Institute of Michigan, PLC	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Canada,  Jordan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	baseline, 4 hours post-dose
Secondary	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.	4 hours post-dose
Secondary	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."	4 hours post-dose
Secondary	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.	baseline, 4 hours post-dosing
Secondary	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".	24 hours post-dosing